日本アレルギー学会、日本皮膚科学会、アトピー性皮膚炎診療ガイドライン作成員会編：アトピー性皮膚炎診療ガイドライン2021.アレルギー：70(10),1257-1342. 2021.
Yusei Ohshima, Akiko Yamada, Masahiro Hiraoka, Kenji Katamura, Setsuko Ito, Takao Hirao, Hiroshi Akutagawa, Naomi Kondo, Akihiro Morikawa, Mitsufumi Mayumi
Early sensitization to house dust mite is a major risk factor for subsequent development of bronchial asthma in Japanese infants with atopic dermatitis: results of a 4-year followup study.
Ann Allergy Asthma Immunol. 2002 Sep;89(3):265-70. doi: 10.1016/S1081-1206(10)61953-9.
Abstract/Text
BACKGROUND: Bronchial asthma (BA) often develops in children with atopic dermatitis (AD). Identification of factors that could predict the development of asthma in children with AD is useful for early intervention.
OBJECTIVE: We undertook a 4-year followup study to clarify the factors involved in the development of BA in infants with AD.
METHODS: We registered 169 infants with AD who were free of BA at registration and examined the prevalence and characteristics of the subsequent development of BA among these patients.
RESULTS: Among the patients followed for 4 years, approximately 45% experienced asthma-like respiratory symptoms, and 35% were diagnosed as asthmatic patients by pediatric allergologists. Patients who developed BA showed early appearance of house dust mite (HDM)-specific immunoglobulin E (IgE) and persistently high levels of food-specific IgE. Male sex, a positive family history of BA, and the appearance of HDM-specific IgE were identified as significant risk factors for the early development of BA, but the significance of these parameters decreased thereafter. A positive family history of AD, the outcome of skin lesions, and keeping furred pets were also identified as risk factors in a part of the followup period. Among the parameters examined, the early appearance of HDM-specific IgE was the most significant risk factor.
CONCLUSION: Appearance of HDM-specific IgE antibodies in early childhood, which seems to be mainly influenced by genetic factors, is a major risk factor for the subsequent development of BA in children with AD, but the influence decreases after longer followup.
Hidehisa Saeki, Yuichiro Tsunemi, Hideki Fujita, Shinji Kagami, Kiyo Sasaki, Hanako Ohmatsu, Aya Watanabe, Kunihiko Tamaki
Prevalence of atopic dermatitis determined by clinical examination in Japanese adults.
J Dermatol. 2006 Nov;33(11):817-9. doi: 10.1111/j.1346-8138.2006.00187.x.
Abstract/Text
日本皮膚科学会、日本アレルギー学会、アトピー性皮膚炎診療ガイドライン作成委員会編：アトピー性皮膚炎診療ガイドライン2021, 日本皮膚科学会雑誌, 131(13); 2691-2777, 2021.
J M Maloney, M R Morman, D M Stewart, M D Tharp, J J Brown, R Rajagopalan
Clobetasol propionate emollient 0.05% in the treatment of atopic dermatitis.
Int J Dermatol. 1998 Feb;37(2):142-4.
Abstract/Text
A 4-week, double-blind, randomized clinical trial, comparing the efficacy and safety of clobetasol propionate emollient cream 0.05% and its vehicle, was conducted at four private dermatology clinics in 81 non-hospitalized patients (> or = 12 years old) with moderate-to-severe atopic dermatitis covering 2% or more of their body surface. All patients had at least one lesion 2 cm or more in diameter. Three signs/symptoms of target lesions (erythema, pruritus, and induration/papulation) were scored by investigators on a scale of 0-3 (in 0.5-point increments; 0 = absent, 1 = mild, 2 = moderate, and 3 = severe); the total of the three scores had to be > or = 6 for patients to qualify for study entry. Patients were excluded if they were immunocompromised, pregnant, or nursing; had skin atrophy, telangiectasia or striae in skin areas to be treated; or had received topical treatments for atopic dermatitis within 1 week prestudy, intramuscular triamcinolone within 6 weeks prestudy, or long-term systemic corticosteroid usage within 6 months prestudy. Patients were randomized in a 1:1 ratio to receive either clobetasol propionate emollient 0.05% twice daily (n = 41), or the emollient vehicle twice daily (n = 40), for 4 weeks. A fingertip unit, equaling approximately 0.5 g in males and 0.43 g in females (enough to cover approximately 2% of the body), was used to measure and apply a thin film of study drug to the affected areas. The efficacy was evaluated by investigators and patients on days 4, 8, 15, and 29 after initiation of therapy, and 2 weeks after the end of treatment (day 43). Investigators performed a physician's gross assessment based on the percentage improvement of the target lesion. They also rated changes from baseline in mean severity scores for six individual signs/symptoms (erythema, pruritus, induration/papulation, lichenification, erosion/oozing/crusting, and scaling/dryness) and for total signs/symptoms according to the severity scoring system described above. Patients rated their response to treatment as excellent, good, fair, poor, or worse. Laboratory assessments were made on days 15, 29, and (if necessary) day 43.
John Berth-Jones, Robert J Damstra, Stefan Golsch, John K Livden, Oliver Van Hooteghem, Fulvio Allegra, Christine A Parker, Multinational Study Group
Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study.
BMJ. 2003 Jun 21;326(7403):1367. doi: 10.1136/bmj.326.7403.1367.
Abstract/Text
OBJECTIVE: To explore the efficacy and safety of fluticasone propionate, cream and ointment, applied twice weekly in addition to maintenance treatment with emollients, in reducing the risk of relapse of chronic recurrent atopic dermatitis.
DESIGN: Randomised, double blind, parallel group study of 20 weeks' duration.
SETTING: Dermatology outpatient clinics (6 countries, 39 centres).
PARTICIPANTS: Adult (aged 12-65) patients with moderate to severe atopic dermatitis who were experiencing a flare.
METHODS: Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks to stabilise their condition. The patients whose disease was brought under control then continued into a 16 week maintenance phase, applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base (emollient alone) twice weekly to the areas that were usually affected.
MAIN OUTCOME MEASURE: Time to relapse of atopic dermatitis during maintenance phase.
RESULTS: 376 patients entered the stabilisation phase, and 295 continued into the maintenance phase. After 16 weeks in the maintenance phase, the disease remained under control in 133 patients (87 using fluticasone propionate twice weekly, 46 using emollient alone), 135 (40 fluticasone propionate, 95 emollient) had experienced a relapse, and 27 had discontinued. Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate. Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely (95% confidence interval 3.1 to 10.8, P < 0.001) and patients using fluticasone propionate ointment 1.9 times less likely (1.2 to 3.2, P=0.010) to have a relapse than patients applying emollient alone. The groups showed no differences in adverse events.
CONCLUSION: After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse.
R Garside, K Stein, E Castelnuovo, M Pitt, D Ashcroft, P Dimmock, L Payne
The effectiveness and cost-effectiveness of pimecrolimus and tacrolimus for atopic eczema: a systematic review and economic evaluation.
Health Technol Assess. 2005 Jul;9(29):iii, xi-xiii,1-230.
Abstract/Text
OBJECTIVES: To consider the effectiveness and cost-effectiveness of pimecrolimus for mild to moderate atopic eczema and tacrolimus for moderate to severe atopic eczema compared with current standard treatment in adults and children.
DATA SOURCES: Electronic databases. Experts and the manufacturers of these agents were also approached for information.
REVIEW METHODS: The systematic review was carried out using standard methodological guidelines and a stringent quality assessment strategy. A state transition (Markov) model was developed to estimate cost--utility of tacrolimus and pimecrolimus separately, compared with current standard practice with topical corticosteroids, (a) as first-line treatment and (b) as second-line treatment. Pimecrolimus was also compared to emollients only.
RESULTS: The pimecrolimus trial reports were of varying quality; however when compared with a placebo (emollient), pimecrolimus was found to be more effective and to provide quality of life improvements. There is very little evidence available about pimecrolimus compared with topical corticosteroids. Compared with a placebo (emollient), both 0.03% and 0.1% tacrolimus were found to be more effective. Compared with a mild corticosteroid, 0.03% tacrolimus is more effective in children as measured by a 90% or better improvement in the Physician's Global Evaluation (PGE). Compared with potent topical corticosteroids, no significant difference in effectiveness is seen with 0.1% tacrolimus as measured by a 75% or greater improvement in the PGE. Minor application site adverse effects are common with tacrolimus. However, this did not lead to increased rates of withdrawal from treatment in trial populations. The PenTag economic model demonstrates a large degree of uncertainty, which was explored in both deterministic and stochastic analyses. This is the case for the cost-effectiveness of pimecrolimus and tacrolimus in first- or second-line use compared with topical steroids. In all cases immunosuppressant regimes were estimated to be more costly than alternatives and differences in benefits to be small and subject to considerable uncertainty.
CONCLUSIONS: There is limited evidence from a small number of randomised controlled trials (RCTs) that pimecrolimus is more effective than placebo treatment in controlling mild to moderate atopic eczema. Although greater than for pimecrolimus, the evidence base for tacrolimus in moderate to severe atopic eczema is also limited. At both 0.1% and 0.03% potencies, tacrolimus appears to be more effective than the placebo treatment and mild topical corticosteroids. However, these are not the most clinically relevant comparators. Compared with potent topical corticosteroids, no significant difference was shown. Short-term adverse effects with both immunosuppressants are relatively common, but appear to be mild. Experience of long-term use of the agents is lacking so the risk of rare but serious adverse effects remains unknown. No conclusions can be confidently drawn about the cost-effectiveness of pimecrolimus or tacrolimus compared with active topical corticosteroid comparators. Areas for further research should focus on the effectiveness and safety of the treatments through good-quality RCTs and further economic analysis.
Mohammad Maged Y El-Batawy, Manal A-W Bosseila, Heba M Mashaly, Vanessa Suzan G A Hafez
Topical calcineurin inhibitors in atopic dermatitis: a systematic review and meta-analysis.
J Dermatol Sci. 2009 May;54(2):76-87. doi: 10.1016/j.jdermsci.2009.02.002. Epub 2009 Mar 20.
Abstract/Text
OBJECTIVES: To build a critical appraisal of the available literature to evaluate the effectiveness of topical calcineurin inhibitors in treatment of atopic dermatitis (AD), in comparison to topical corticosteroids (TCs) and/or placebo.
REVIEW METHODS:
DESIGN: systematic review and meta-analysis.
DATA SOURCES: electronic search of MEDLINE Pubmed along the last 10 years (1997-2006).
STUDY SELECTION: randomized control trials of TCIs reporting efficacy outcomes, in comparison to TCs or vehicle (placebo) or both.
DATA SYNTHESIS: of 210 articles, 19 studies were included, 10 for tacrolimus and 9 for pimecrolimus, involving 7378 patients of whom 2771 applied tacrolimus, 1783 applied pimecrolimus, and 2824 were controls. Both drugs were significantly more effective than a vehicle. However, two long-term trials comparing demonstrated the value of pimecrolimus in reduction of flares and steroid-sparing effect after 6 months. Compared to TCs, both 0.1% and 0.03% tacrolimus ointments were as effective as moderate potency TCs, and more effective than a combined steroid regimen. Tacrolimus was more effective than mild TCs.
CONCLUSIONS: TCIs in AD are more effective than placebo. Although less effective than TCs, pimecrolimus has its value in long-term maintenance and as a steroid-sparing agent in AD, whenever used early enough, at first appearance of erythema and/or itching. In treatment of moderate to severe AD, topical tacrolimus is as effective as moderately potent TCs, and more effective than mild preparations. Chronic AD lesions of the face and flexures are the most justified indication for topical calcineurin inhibitors.
Felix M Arellano, Charles E Wentworth, Alejandro Arana, Carlos Fernández, Carle F Paul
Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis.
J Invest Dermatol. 2007 Apr;127(4):808-16. doi: 10.1038/sj.jid.5700622. Epub 2006 Nov 9.
Abstract/Text
Systemic use of immunosuppressant agents increases the risk of lymphoma in transplantation. We performed a nested case-control study in the PharMetrics database to evaluate the association between topical immunosuppressants and lymphoma in a cohort of patients with atopic dermatitis. We identified cases of lymphoma and randomly selected four controls for each case, matched by length of follow-up. We used conditional logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CIs) of the association between topical immunosuppressants and lymphoma. Two hundred and ninety-four cases of lymphoma occurred in 293,253 patients, 81 in patients younger than 20 years. The adjusted analysis yielded the following OR (95%CI) for: severity (OR 2.4; 95% CI 1.5-3.8), oral steroids 1.5 (1.0-2.4), "super potent" topical steroids 1.2 (0.8-1.8) , "low potency" topical steroids OR 1.1 (0.7-1.6); pimecrolimus 0.8(0.4-1.6), tacrolimus OR 0.8 (0.4-1.7), and concomitant topical steroids, pimecrolimus, and tacrolimus 1.0 (0.3-4.1). We did not find an increased risk of lymphoma in patients treated with topical calcineurin inhibitors. It is difficult to disentangle the effects of severity of disease on outcome versus the true effects of drugs. However, in the adjusted analysis, severity of AD was the main factor associated with an increased risk of lymphoma.
M Kawashima, T Tango, T Noguchi, M Inagi, H Nakagawa, S Harada
Addition of fexofenadine to a topical corticosteroid reduces the pruritus associated with atopic dermatitis in a 1-week randomized, multicentre, double-blind, placebo-controlled, parallel-group study.
Br J Dermatol. 2003 Jun;148(6):1212-21.
Abstract/Text
BACKGROUND: Fexofenadine, a nonsedating, H1-receptor selective antihistamine, exhibits consistent efficacy and safety in the treatment of allergic rhinitis and urticaria. The pruritus associated with atopic dermatitis is considered to be induced, in part, by histamine. Therefore, we thought that fexofenadine may be useful in the relief of pruritus associated with atopic dermatitis.
OBJECTIVE: To compare the efficacy of twice-daily fexofenadine hydrochloride (HCl) 60 mg vs. placebo in reducing the pruritus associated with atopic dermatitis.
METHODS: In this randomized, multicentre, double-blind, placebo-controlled study, patients (aged >or= 16 years) with atopic dermatitis underwent a 1-week placebo lead-in period, followed by randomization to fexofenadine HCl 60 mg twice daily or placebo for 1 week. All patients also received topical treatment with 0.1% hydrocortisone butyrate twice daily throughout the study. The primary efficacy endpoint was mean change in pruritus score from baseline. Patients reflectively recorded pruritus scores twice daily (day and night) using a five-point scale (0 = none; 4 = very severe).
RESULTS: Fexofenadine (n = 201) significantly decreased the severity of pruritus compared with placebo (n = 199) (mean change in score -0.75 (unadjusted 95% confidence interval [-0.88, -0.62]) vs. -0.5 [-0.62, -0.38], respectively; P = 0.0005). This improvement was seen after just 1 day of treatment (P = 0.039) and was maintained throughout the treatment period (P = 0.019). Compared with placebo, fexofenadine significantly improved both diurnal (P = 0.0001) and nocturnal pruritus (P = 0.013). In addition, significantly more patients in the fexofenadine group experienced a reduction in the ratio of pruritus area to body surface area compared with those in the placebo group (P = 0.007). The incidence of adverse events was low and similar across all treatment groups.
CONCLUSIONS: Fexofenadine HCl 60 mg twice daily demonstrated a rapid, significant improvement in the pruritus associated with atopic dermatitis, with a safety profile equivalent to that of placebo.
Uwe Matterne, Merle Margarete Böhmer, Elke Weisshaar, Aldrin Jupiter, Ben Carter, Christian J Apfelbacher
Oral H1 antihistamines as 'add-on' therapy to topical treatment for eczema.
Cochrane Database Syst Rev. 2019 Jan 22;1(1):CD012167. doi: 10.1002/14651858.CD012167.pub2. Epub 2019 Jan 22.
Abstract/Text
BACKGROUND: The symptoms of eczema can lead to sleeplessness and fatigue and may have a substantial impact on quality of life. Use of oral H1 antihistamines (H1 AH) as adjuvant therapy alongside topical agents is based on the idea that combining the anti-inflammatory effects of topical treatments with the blocking action of histamine on its receptors in the skin by H1 AH (to reduce the principal symptom of itch) might magnify or intensify the effect of treatment. Also, it would be unethical to compare oral H1 AH alone versus no treatment, as topical treatment is the standard management for this condition.
OBJECTIVES: To assess the effects of oral H1 antihistamines as 'add-on' therapy to topical treatment in adults and children with eczema.
SEARCH METHODS: We searched the following databases up to May 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and the GREAT database (Global Resource of EczemA Trials; from inception). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We also searched the abstracts of four conference proceedings held between 2000 and 2018.
SELECTION CRITERIA: We sought RCTs assessing oral H1 AH as 'add-on' therapy to topical treatment for people with eczema compared with topical treatment plus placebo or no additional treatment as add-on therapy.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcome measures were 'Mean change in patient-assessed symptoms of eczema' and 'Proportion of participants reporting adverse effects and serious adverse events'. Secondary outcomes were 'Mean change in physician-assessed clinical signs', 'Mean change in quality of life', and 'Number of eczema flares'.
MAIN RESULTS: We included 25 studies (3285 randomised participants). Seventeen studies included 1344 adults, and eight studies included 1941 children. Most studies failed to report eczema severity at baseline, but they were conducted in secondary care settings, so it is likely that they recruited patients with more severe cases of eczema. Trial duration was between three days and 18 months. Researchers studied 13 different H1 AH treatments. We could not undertake pooling because of the high level of diversity across studies in terms of duration and dose of intervention, concomitant topical therapy, and outcome assessment. Risk of bias was generally unclear, but five studies had high risk of bias in one domain (attrition, selection, or reporting bias). Only one study measured quality of life, but these results were insufficient for statistical analysis.Although this review assessed 17 comparisons, we summarise here the results of three key comparisons in this review.Cetirizine versus placeboOne study compared cetirizine 0.5 mg/kg/d against placebo over 18 months in 795 children. Study authors did not report patient-assessed symptoms of eczema separately for pruritus. Cetirizine is probably associated with fewer adverse events (mainly mild) (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.46 to 1.01) and the need for slightly less additional H1 AH use as an indication of eczema flare rate (P = 0.035; no further numerical data given). Physician-assessed clinical signs (SCORing Atopic Dermatitis index (SCORAD)) were reduced in both groups, but the difference between groups was reported as non-significant (no P value given). Evidence for this comparison was of moderate quality.One study assessed cetirizine 10 mg/d against placebo over four weeks in 84 adults. Results show no evidence of differences between groups in patient-assessed symptoms of eczema (pruritus measured as part of SCORAD; no numerical data given), numbers of adverse events (RR 1.11, 95% CI 0.50 to 2.45; mainly sedation, other skin-related problems, respiratory symptoms, or headache), or physician-assessed changes in clinical signs, amount of local rescue therapy required, or number of applications as an indicator of eczema flares (no numerical data reported). Evidence for this comparison was of low quality.Fexofenadine versus placeboCompared with placebo, fexofenadine 120 mg/d taken in adults over one week (one study) probably leads to a small reduction in patient-assessed symptoms of pruritus on a scale of 0 to 8 (mean difference (MD) -0.25, 95% CI -0.43 to -0.07; n = 400) and a greater reduction in the ratio of physician-assessed pruritus area to whole body surface area (P = 0.007; no further numerical data given); however, these reductions may not be clinically meaningful. Results suggest probably little or no difference in adverse events (mostly somnolence and headache) (RR 1.05, 95% CI 0.74 to 1.50; n = 411) nor in the amount of 0.1% hydrocortisone butyrate used (co-intervention in both groups) as an indicator of eczema flare, but no numerical data were given. Evidence for this comparison was of moderate quality.Loratadine versus placeboA study of 28 adults compared loratadine 10 mg/d taken over 4 weeks versus placebo. Researchers found no evidence of differences between groups in patient-assessed pruritus, measured by a 100-point visual analogue scale (MD -2.30, 95% CI -20.27 to 15.67); reduction in physician-assessed clinical signs (SCORAD) (MD -4.10, 95% CI -13.22 to 5.02); or adverse events. Study authors reported only one side effect (folliculitis with placebo) (RR 0.25, 95% CI 0.01 to 5.76). Evidence for this comparison was of low quality. Number of eczema flares was not measured for this comparison.
AUTHORS' CONCLUSIONS: Based on the main comparisons, we did not find consistent evidence that H1 AH treatments are effective as 'add-on' therapy for eczema when compared to placebo; evidence for this comparison was of low and moderate quality. However, fexofenadine probably leads to a small improvement in patient-assessed pruritus, with probably no significant difference in the amount of treatment used to prevent eczema flares. Cetirizine was no better than placebo in terms of physician-assessed clinical signs nor patient-assessed symptoms, and we found no evidence that loratadine was more beneficial than placebo, although all interventions seem safe.The quality of evidence was limited because of poor study design and imprecise results. Future researchers should clearly define the condition (course and severity) and clearly report their methods, especially participant selection and randomisation; baseline characteristics; and outcomes (based on the Harmonising Outcome Measures in Eczema initiative).
J Munday, R Bloomfield, M Goldman, H Robey, G J Kitowska, Z Gwiezdziski, A Wankiewicz, R Marks, F Protas-Drozd, M Mikaszewska
Chlorpheniramine is no more effective than placebo in relieving the symptoms of childhood atopic dermatitis with a nocturnal itching and scratching component.
Dermatology. 2002;205(1):40-5.
Abstract/Text
BACKGROUND: Childhood atopic dermatitis (AD) is a common disorder affecting 15% of children aged over 18 months. AD is associated with intense nocturnal itching. The central sedative effect of antihistamines is thought to be useful in interrupting the itching cycle and may prevent exacerbations.
OBJECTIVE: A multi-centred, double-blind, placebo-controlled study was carried out in 155 children to evaluate chlorpheniramine in alleviating symptoms of AD.
METHODS: Assessments were carried out over a 4-week study period consisting of 3 visits to out-patient clinics. During the visits the severity of AD and itching was rated using a series of visual analogue scale (VAS) and 5-point rating scales.
RESULTS: The use of chlorpheniramine resulted in no greater alleviation of AD symptoms than placebo.
CONCLUSIONS: The findings contradict conventional wisdom that the sedative effect of earlier-generation antihistamines alleviates symptoms of AD. The study also indicates that the use of antihistamines in AD does not affect the amounts of topical treatment used over the short term.
Copyright 2002 S. Karger AG, Basel
K Wirén, C Nohlgård, F Nyberg, L Holm, M Svensson, A Johannesson, P Wallberg, B Berne, F Edlund, M Lodén
Treatment with a barrier-strengthening moisturizing cream delays relapse of atopic dermatitis: a prospective and randomized controlled clinical trial.
J Eur Acad Dermatol Venereol. 2009 Nov;23(11):1267-72. doi: 10.1111/j.1468-3083.2009.03303.x. Epub 2009 Jun 8.
Abstract/Text
BACKGROUND: Standard treatment of atopic dermatitis (AD) is based on topical glucocorticosteroids or calcineurin inhibitors to treat flares combined with moisturizer treatment to alleviate dry skin symptoms. Patients with AD have an abnormal skin barrier function, and strategies for reducing the risks for eczema would be to repair the barrier or prevent barrier dysfunction.
OBJECTIVES: The objective of this study was to explore the time to relapse of eczema during a 26-week maintenance treatment with a urea containing moisturizer compared to no treatment (neither medical nor non-medicated preparations) after successful clearing of atopic lesions. The moisturizer has previously been shown to improve skin barrier function.
METHODS: Patients applied betamethasone valerate (0.1%) on eczematous lesions during a 3-week period. Those with cleared eczema entered a 26-week maintenance phase, applying the moisturizer or left the previously affected area untreated. Upon eczema relapse, patients were instructed to contact the clinic and to have the relapse confirmed by the investigator.
RESULTS: Fifty-five patients entered the study and 44 patients were included in the maintenance phase (22 using moisturizer twice daily and 22 using no treatment). Median time to relapse for patients treated with moisturizer was > 180 days (duration of the study) compared with 30 days for the no-treatment group. Sixty-eight per cent of the patients treated with the moisturizer and 32% of the untreated patients remained free from eczema during the observation period.
CONCLUSIONS: Maintenance treatment with a barrier-improving urea moisturizer on previous eczematous areas reduced the risk of relapse to approximately one third of that of no treatment.
Philippe Msika, Clarence De Belilovsky, Nathalie Piccardi, Nathalie Chebassier, Caroline Baudouin, Bernard Chadoutaud
New emollient with topical corticosteroid-sparing effect in treatment of childhood atopic dermatitis: SCORAD and quality of life improvement.
Pediatr Dermatol. 2008 Nov-Dec;25(6):606-12. doi: 10.1111/j.1525-1470.2008.00783.x.
Abstract/Text
Emollients are commonly used for their effectiveness on atopic skin, supported by a few clinical studies suggesting their potential role as corticosteroid sparing agents. We investigated the effect of a new natural emollient on corticosteroid sparing and quality of life of young atopic children and their family. Eighty-six patients (4-48 mos) with moderate atopic dermatitis were randomized by 20 pediatricians to five groups for 21 days: corticosteroids (from twice daily to one application every other day) combined or not with the studied cream (twice daily), and evaluated by SCORAD and specific quality of life questionnaires. At the end of the study, all five groups were statistically improved in terms of SCORAD and quality of life index. Thus, application of a topical corticosteroid every other day in addition to the studied cream was as effective as a once or twice daily application of the steroid alone. The studied cream had a significant impact on lichenification, excoriation and quality of life. A twice daily application of a new natural emollient provided a major corticosteroid sparing, improved lichenification and excoriation and improved the quality of life in children and their parents.
川島眞, 林伸和, 乃木田俊辰, 他：アトピー性皮膚炎の寛解維持における保湿剤の有用性の検討．日皮会誌, 2007;117: 1139-1145.
Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials.
Br J Dermatol. 2011 Feb;164(2):415-28. doi: 10.1111/j.1365-2133.2010.10030.x. Epub 2010 Nov 23.
Abstract/Text
中村晃一郎, 二村昌樹, 常深祐一郎, 種瀬啓士, 加藤則人：デルゴシチニブ軟膏（コレクチム®軟膏0.5％）安全使用マニュアル．日皮会誌, 130（7）; 1581-1588, 2020.
Hidemi Nakagawa, Osamu Nemoto, Atsuyuki Igarashi, Hidehisa Saeki, Hironobu Kaino, Takeshi Nagata
Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study.
J Am Acad Dermatol. 2020 Apr;82(4):823-831. doi: 10.1016/j.jaad.2019.12.015. Epub 2020 Feb 3.
Abstract/Text
BACKGROUND: Previous studies showed the potential effectiveness of delgocitinib ointment, a novel topical Janus kinase inhibitor, in atopic dermatitis (AD).
OBJECTIVE: This study aimed to evaluate the efficacy and safety of delgocitinib 0.5% ointment.
METHODS: In part 1, a 4-week double-blind period, Japanese patients aged 16 years or older with moderate or severe AD were randomly assigned in a 2:1 ratio to delgocitinib 0.5% ointment or vehicle ointment. Eligible patients entered part 2, a 24-week extension period, to receive delgocitinib 0.5% ointment.
RESULTS: At the end of treatment in part 1, the least-squares mean percent changes from baseline in the modified Eczema Area and Severity Index score, the primary efficacy endpoint, were significantly greater in the delgocitinib group than in the vehicle group (-44.3% vs 1.7%, P < .001). The improvement in modified Eczema Area and Severity Index score was maintained in part 2. Most adverse events were mild and unrelated to delgocitinib across the study periods.
LIMITATIONS: Only Japanese patients were included. The vehicle-controlled period lasted only 4 weeks. In part 2, topical corticosteroids were allowed for the treatment of worsening of AD.
CONCLUSION: Delgocitinib ointment was effective and well tolerated in Japanese adult patients with moderate to severe AD for up to 28 weeks.
Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Hidemi Nakagawa, Osamu Nemoto, Atsuyuki Igarashi, Hidehisa Saeki, Kenji Kabashima, Manabu Oda, Takeshi Nagata
Delgocitinib ointment in pediatric patients with atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and a subsequent open-label, long-term study.
J Am Acad Dermatol. 2021 Oct;85(4):854-862. doi: 10.1016/j.jaad.2021.06.014. Epub 2021 Jun 10.
Abstract/Text
BACKGROUND: Delgocitinib 0.5% ointment, a topical Janus kinase inhibitor, has been approved in Japan for adult patients with atopic dermatitis (AD).
OBJECTIVE: To evaluate the efficacy and safety of delgocitinib ointment in pediatric patients with AD.
METHODS: Part 1 of this study was a 4-week double-blind period in which Japanese patients aged 2 through 15 years were randomized in a 1:1 ratio to delgocitinib 0.25% ointment or vehicle ointment. Part 2 was a 52-week extension period. Eligible patients entered part 2 to receive 0.25% or 0.5% delgocitinib ointment.
RESULTS: At the initiation of the study, approximately half of the patients had moderate AD. At the end of treatment in part 1, the least-squares mean percent change from baseline in modified Eczema Area and Severity Index score, the primary efficacy endpoint, was significantly greater for delgocitinib ointment than for vehicle (-39.3% vs +10.9%, P < .001). In part 2, improvements in AD were also seen through week 56. Most adverse events were mild and unrelated to delgocitinib across the study periods.
LIMITATIONS: Only Japanese patients were included. In part 2, no control group was included and rescue therapy was allowed.
CONCLUSION: Delgocitinib ointment was effective and well tolerated when applied to Japanese pediatric patients with AD for up to 56 weeks.
Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Hidemi Nakagawa, Osamu Nemoto, Atsuyuki Igarashi, Hidehisa Saeki, Kenji Kabashima, Manabu Oda, Takeshi Nagata
Delgocitinib ointment in pediatric patients with atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and a subsequent open-label, long-term study.
J Am Acad Dermatol. 2021 Oct;85(4):854-862. doi: 10.1016/j.jaad.2021.06.014. Epub 2021 Jun 10.
Abstract/Text
BACKGROUND: Delgocitinib 0.5% ointment, a topical Janus kinase inhibitor, has been approved in Japan for adult patients with atopic dermatitis (AD).
OBJECTIVE: To evaluate the efficacy and safety of delgocitinib ointment in pediatric patients with AD.
METHODS: Part 1 of this study was a 4-week double-blind period in which Japanese patients aged 2 through 15 years were randomized in a 1:1 ratio to delgocitinib 0.25% ointment or vehicle ointment. Part 2 was a 52-week extension period. Eligible patients entered part 2 to receive 0.25% or 0.5% delgocitinib ointment.
RESULTS: At the initiation of the study, approximately half of the patients had moderate AD. At the end of treatment in part 1, the least-squares mean percent change from baseline in modified Eczema Area and Severity Index score, the primary efficacy endpoint, was significantly greater for delgocitinib ointment than for vehicle (-39.3% vs +10.9%, P < .001). In part 2, improvements in AD were also seen through week 56. Most adverse events were mild and unrelated to delgocitinib across the study periods.
LIMITATIONS: Only Japanese patients were included. In part 2, no control group was included and rescue therapy was allowed.
CONCLUSION: Delgocitinib ointment was effective and well tolerated when applied to Japanese pediatric patients with AD for up to 56 weeks.
Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Hidemi Nakagawa, Atsuyuki Igarashi, Hidehisa Saeki, Kenji Kabashima, Tomomi Tamaki, Hironobu Kaino, Yasushi Miwa
Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study.
Allergol Int. 2024 Jan;73(1):137-142. doi: 10.1016/j.alit.2023.04.003. Epub 2023 Apr 24.
Abstract/Text
BACKGROUND: Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established.
METHODS: This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion.
RESULTS: A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were -73.5% at week 4, -81.7% at week 28, and -81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%-95.2%).
CONCLUSIONS: Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.
Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.
Hidemi Nakagawa, Atsuyuki Igarashi, Hidehisa Saeki, Kenji Kabashima, Tomomi Tamaki, Hironobu Kaino, Yasushi Miwa
Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study.
Allergol Int. 2024 Jan;73(1):137-142. doi: 10.1016/j.alit.2023.04.003. Epub 2023 Apr 24.
Abstract/Text
BACKGROUND: Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established.
METHODS: This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion.
RESULTS: A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were -73.5% at week 4, -81.7% at week 28, and -81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%-95.2%).
CONCLUSIONS: Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.
Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.
H Saeki, N Baba, K Ito, D Yokota, H Tsubouchi
Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial.
Br J Dermatol. 2022 Jan;186(1):40-49. doi: 10.1111/bjd.20655. Epub 2021 Nov 1.
Abstract/Text
BACKGROUND: In atopic dermatitis (AD), phosphodiesterase 4 (PDE4) inhibition reduces proinflammatory mediators and cytokines. Difamilast is a new selective PDE4 inhibitor.
OBJECTIVES: To demonstrate the superiority of topical difamilast to vehicle in Japanese paediatric patients with AD.
METHODS: This was a phase III randomized, double-blind, vehicle-controlled trial. Patients aged 2-14 years with an Investigator Global Assessment (IGA) score of 2 or 3 received difamilast 0·3% (n = 83), difamilast 1% (n = 85) or vehicle (n = 83) ointment twice daily for 4 weeks.
RESULTS: The primary endpoint was the percentage of patients with an IGA score of 0 or 1 with improvement by at least two grades at week 4. The success rates in IGA score at week 4 were 44·6%, 47·1% and 18·1% in the difamilast 0·3%, difamilast 1% and vehicle groups, respectively. Both difamilast groups demonstrated significantly higher success rates in IGA score compared with vehicle at week 4 [difamilast 0·3% (P < 0·001); difamilast 1% (P < 0·001)]. Regarding secondary endpoints, improvements in Eczema Area and Severity Index (EASI; improvement of ≥ 50%, ≥ 75% and ≥ 90% in overall score) at week 4 were significantly higher in patients in the difamilast 0·3% and 1% groups than those in the vehicle group. EASI score in the difamilast 0·3% and 1% groups was significantly reduced compared with that of patients in the vehicle group at week 1. The significant difference between both the difamilast groups and the vehicle groups was maintained from week 1 through to week 4. Most treatment-emergent adverse events were mild or moderate, and no serious events or deaths were reported.
CONCLUSIONS: Difamilast 0·3% and 1% ointments are superior to vehicle and well tolerated in Japanese paediatric patients with AD.
© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
モイゼルト軟膏0.3%・1%適正使用について [Internet]. Available from: https://www.otsuka-elibrary.jp/pdf_viewer/?f=/product/di/mz1/tekisei/file/mz1_teki_01.pdf
モイゼルト軟膏0.3%・1%適正使用について [Internet]. Available from: https://www.otsuka-elibrary.jp/pdf_viewer/?f=/product/di/mz1/tekisei/file/mz1_teki_01.pdf
C C Long, A Y Finlay
The finger-tip unit--a new practical measure.
Clin Exp Dermatol. 1991 Nov;16(6):444-7.
Abstract/Text
A finger-tip unit (FTU) is the amount of ointment expressed from a tube with a 5 mm diameter nozzle, applied from the distal skin-crease to the tip of the index finger. Thirty adult-patients treated various anatomical regions using FTU's of ointment. The number of FTU's required was: face and neck 2.5 (s.d. +/- 0.8); front of trunk 6.7 (s.d. +/- 1.7); back of trunk 6.8 (s.d. +/- 1.2); arm and forearm 3.3 (s.d. +/- 1.0); hand 1.2 (s.d. +/- 0.4); leg and thigh 5.8 (s.d. +/- 1.7); foot 1.8 (s.d. +/- 0.6). One FTU covers 286 cm2 (s.d. +/- 80, n = 30). In males one FTU covers 312 cm2 (s.d. +/- 90, n = 16) and in females 257 cm2 (s.d. +/- 55, n = 14). The use of the FTU in dermatological prescribing provides a readily understandable measure for both patients and doctor.
C C Long, A Y Finlay
The finger-tip unit--a new practical measure.
Clin Exp Dermatol. 1991 Nov;16(6):444-7.
Abstract/Text
A finger-tip unit (FTU) is the amount of ointment expressed from a tube with a 5 mm diameter nozzle, applied from the distal skin-crease to the tip of the index finger. Thirty adult-patients treated various anatomical regions using FTU's of ointment. The number of FTU's required was: face and neck 2.5 (s.d. +/- 0.8); front of trunk 6.7 (s.d. +/- 1.7); back of trunk 6.8 (s.d. +/- 1.2); arm and forearm 3.3 (s.d. +/- 1.0); hand 1.2 (s.d. +/- 0.4); leg and thigh 5.8 (s.d. +/- 1.7); foot 1.8 (s.d. +/- 0.6). One FTU covers 286 cm2 (s.d. +/- 80, n = 30). In males one FTU covers 312 cm2 (s.d. +/- 90, n = 16) and in females 257 cm2 (s.d. +/- 55, n = 14). The use of the FTU in dermatological prescribing provides a readily understandable measure for both patients and doctor.
Yoshikazu Kameyoshi, Toshihiko Tanaka, Mitsuru Mochizuki, Osamu Koro, Shoji Mihara, Takaaki Hiragun, Maiko Tanaka, Michihiro Hide
[Taking showers at school is beneficial for children with severer atopic dermatitis].
Arerugi. 2008 Feb;57(2):130-7.
Abstract/Text
BACKGROUND: Sweat(ing) is a common aggravating factor of atopic dermatitis (AD), and many school children with AD experience the exacerbation of their disease in summer.
OBJECTIVE: We evaluated the usefulness of taking shower at the school for the management of AD in summer.
METHODS: Fifty-eight school children with moderate or severer atopic dermatitis were enrolled in the study. Subjects were allocated to one of following groups, group A: no shower (n=15), group B: 4-weeks shower (n=22), group C1: 2-weeks shower in the first half (n=11), or group C2: 2-weeks shower in the latter half (n=10), and took (or did not take) shower at the school from the beginning of September. Disease severity was evaluated on day 0, 2 weeks later and 4 weeks later using SCORAD scoring system.
RESULTS: Significant improvements in SCORAD scores after 4 weeks were observed only in groups B and C1. When the subjects were sub-divided by the severity of the disease, the significant effect of shower was limited to the patients with severe and most severe disease. Similar results were obtained with a modified SCORAD score in which subjective symptoms were excluded.
CONCLUSION: It is useful to take showers at the school for the management of AD for the children with severer disease.
Yoshikazu Kameyoshi, Toshihiko Tanaka, Mitsuru Mochizuki, Osamu Koro, Shoji Mihara, Takaaki Hiragun, Maiko Tanaka, Michihiro Hide
[Taking showers at school is beneficial for children with severer atopic dermatitis].
Arerugi. 2008 Feb;57(2):130-7.
Abstract/Text
BACKGROUND: Sweat(ing) is a common aggravating factor of atopic dermatitis (AD), and many school children with AD experience the exacerbation of their disease in summer.
OBJECTIVE: We evaluated the usefulness of taking shower at the school for the management of AD in summer.
METHODS: Fifty-eight school children with moderate or severer atopic dermatitis were enrolled in the study. Subjects were allocated to one of following groups, group A: no shower (n=15), group B: 4-weeks shower (n=22), group C1: 2-weeks shower in the first half (n=11), or group C2: 2-weeks shower in the latter half (n=10), and took (or did not take) shower at the school from the beginning of September. Disease severity was evaluated on day 0, 2 weeks later and 4 weeks later using SCORAD scoring system.
RESULTS: Significant improvements in SCORAD scores after 4 weeks were observed only in groups B and C1. When the subjects were sub-divided by the severity of the disease, the significant effect of shower was limited to the patients with severe and most severe disease. Similar results were obtained with a modified SCORAD score in which subjective symptoms were excluded.
CONCLUSION: It is useful to take showers at the school for the management of AD for the children with severer disease.
Hiroyuki Mochizuki, Reiko Muramatsu, Hiromi Tadaki, Takahisa Mizuno, Hirokazu Arakawa, Akihiro Morikawa
Effects of skin care with shower therapy on children with atopic dermatitis in elementary schools.
Pediatr Dermatol. 2009 Mar-Apr;26(2):223-5. doi: 10.1111/j.1525-1470.2009.00887.x.
Abstract/Text
For elementary school children with atopic dermatitis, a skin care program using shower therapy was performed during the school lunch break for 6 weeks from June to July in 2004 and 2005. All 53 participants showed an improvement in their atopic dermatitis during the 6-week periods studied. Skin care with daily showering at an elementary school was thus found to be effective for the treatment of atopic dermatitis.
Hiroyuki Mochizuki, Reiko Muramatsu, Hiromi Tadaki, Takahisa Mizuno, Hirokazu Arakawa, Akihiro Morikawa
Effects of skin care with shower therapy on children with atopic dermatitis in elementary schools.
Pediatr Dermatol. 2009 Mar-Apr;26(2):223-5. doi: 10.1111/j.1525-1470.2009.00887.x.
Abstract/Text
For elementary school children with atopic dermatitis, a skin care program using shower therapy was performed during the school lunch break for 6 weeks from June to July in 2004 and 2005. All 53 participants showed an improvement in their atopic dermatitis during the 6-week periods studied. Skin care with daily showering at an elementary school was thus found to be effective for the treatment of atopic dermatitis.
Hiromi Kobayashi, Masamitsu Ishii, Satoshi Takeuchi, Yoichi Tanaka, Takahiro Shintani, Atsushi Yamatodani, Tadashi Kusunoki, Masutaka Furue
Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo (Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study.
Evid Based Complement Alternat Med. 2010 Sep;7(3):367-73. doi: 10.1093/ecam/nen003. Epub 2008 Jan 31.
Abstract/Text
Hochu-ekki-to is a traditional herbal (Kampo) medicine that has been shown to be effective for patients with Kikyo (delicate, easily fatigable, or hypersensitive) constitution. Previous case reports have suggested that this herbal drug was effective for a certain subgroup of patients with atopic dermatitis (AD). We aimed to evaluate the efficacy and safety of Hochu-ekki-to in the long-term management of Kikyo patients with AD. In this multicenter, double blind, randomized, placebo-controlled study, 91 Kikyo patients with AD were enrolled. Kikyo condition was evaluated by a questionnaire scoring system. All patients continued their ordinary treatments (topical steroids, topical tacrolimus, emollients or oral antihistamines) before and after their protocol entry. Hochu-ekki-to or placebo was orally administered twice daily for 24 weeks. The skin severity scores, total equivalent amount (TEA) of topical agents used for AD treatment, prominent efficacy (cases with skin severity score = 0 at the end of the study) rate and aggravated rate (more than 50% increase of TEA of topical agents from the beginning of the study) were monitored and evaluated. Seventy-seven out of 91 enrolled patients completed the 24-week treatment course (Hochu-ekki-to: n = 37, placebo: n = 40). The TEA of topical agents (steroids and/or tacrolimus) was significantly (P < 0.05) lower in the Hochu-ekki-to group than in the placebo group, although the overall skin severity scores were not statistically different. The prominent efficacy rate was 19% (7 of 37) in the Hochu-ekki-to group and 5% (2 of 40) in the placebo group (P = 0.06). The aggravated rate was significantly (P < 0.05) lower in the Hochu-ekki-to group (3%; 1 of 37) than in the placebo group (18%; 7 of 39). Only mild adverse events such as nausea and diarrhea were noted in both groups without statistical difference. This placebo-controlled study demonstrates that Hochu-ekki-to is a useful adjunct to conventional treatments for AD patients with Kikyo constitution. Use of Hochu-ekki-to significantly reduces the dose of topical steroids and/or tacrolimus used for AD treatment without aggravating AD.
Hiromi Kobayashi, Masamitsu Ishii, Satoshi Takeuchi, Yoichi Tanaka, Takahiro Shintani, Atsushi Yamatodani, Tadashi Kusunoki, Masutaka Furue
Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo (Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study.
Evid Based Complement Alternat Med. 2010 Sep;7(3):367-73. doi: 10.1093/ecam/nen003. Epub 2008 Jan 31.
Abstract/Text
Hochu-ekki-to is a traditional herbal (Kampo) medicine that has been shown to be effective for patients with Kikyo (delicate, easily fatigable, or hypersensitive) constitution. Previous case reports have suggested that this herbal drug was effective for a certain subgroup of patients with atopic dermatitis (AD). We aimed to evaluate the efficacy and safety of Hochu-ekki-to in the long-term management of Kikyo patients with AD. In this multicenter, double blind, randomized, placebo-controlled study, 91 Kikyo patients with AD were enrolled. Kikyo condition was evaluated by a questionnaire scoring system. All patients continued their ordinary treatments (topical steroids, topical tacrolimus, emollients or oral antihistamines) before and after their protocol entry. Hochu-ekki-to or placebo was orally administered twice daily for 24 weeks. The skin severity scores, total equivalent amount (TEA) of topical agents used for AD treatment, prominent efficacy (cases with skin severity score = 0 at the end of the study) rate and aggravated rate (more than 50% increase of TEA of topical agents from the beginning of the study) were monitored and evaluated. Seventy-seven out of 91 enrolled patients completed the 24-week treatment course (Hochu-ekki-to: n = 37, placebo: n = 40). The TEA of topical agents (steroids and/or tacrolimus) was significantly (P < 0.05) lower in the Hochu-ekki-to group than in the placebo group, although the overall skin severity scores were not statistically different. The prominent efficacy rate was 19% (7 of 37) in the Hochu-ekki-to group and 5% (2 of 40) in the placebo group (P = 0.06). The aggravated rate was significantly (P < 0.05) lower in the Hochu-ekki-to group (3%; 1 of 37) than in the placebo group (18%; 7 of 39). Only mild adverse events such as nausea and diarrhea were noted in both groups without statistical difference. This placebo-controlled study demonstrates that Hochu-ekki-to is a useful adjunct to conventional treatments for AD patients with Kikyo constitution. Use of Hochu-ekki-to significantly reduces the dose of topical steroids and/or tacrolimus used for AD treatment without aggravating AD.
M P Sheehan, M H Rustin, D J Atherton, C Buckley, D W Harris, J Brostoff, L Ostlere, A Dawson, D J Harris
Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis.
Lancet. 1992 Jul 4;340(8810):13-7.
Abstract/Text
There has been considerable interest in traditional Chinese herbal therapy (TCHT) as a new treatment for atopic dermatitis. To establish the efficacy and safety of this treatment, a daily decoction of a formula containing ten herbs that has been found to be beneficial in open studies was tested in a double-blind placebo-controlled study. 40 adult patients with longstanding, refractory, widespread, atopic dermatitis were randomised into two groups to receive 2 months' treatment of either the active formulation of herbs (TCHT) or placebo herbs, followed by a crossover to the other treatment after a 4-week washout period. The main outcome measures were extent and severity of erythema and surface damage as judged by standardised body scores. The patients' own assessments of the overall response to treatment were also sought. The geometric mean score for erythema at the end of active treatment was 12.6 (95% confidence interval [CI] 5.9 to 22.0) and at the end of the placebo phase was 113 (65 to 180). The geometric mean score for surface damage was 11.3 (5.8 to 21.8) and 111.0 (68 to 182), respectively. The 95% CI for the mean geometric ratio for the two values with active treatment was 0.04 to 0.22 for erythema (p less than 0.0005) and 0.04 to 0.27 for surface damage (p less than 0.0005). Of the 31 patients who completed the study and expressed a preference, 20 preferred that phase of the trial in which they received TCHT whereas 4 patients preferred placebo (p less than 0.02). There was a subjective improvement in itching (p less than 0.001) and sleep (p less than 0.078) during the TCHT treatment phase. No side-effects were reported by the patients although many commented on the unpalatability of the decoction. TCHT seems to benefit patients with atopic dermatitis. Palatability of the treatment needs to be improved and its safety assured.
M P Sheehan, M H Rustin, D J Atherton, C Buckley, D W Harris, J Brostoff, L Ostlere, A Dawson, D J Harris
Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis.
Lancet. 1992 Jul 4;340(8810):13-7.
Abstract/Text
There has been considerable interest in traditional Chinese herbal therapy (TCHT) as a new treatment for atopic dermatitis. To establish the efficacy and safety of this treatment, a daily decoction of a formula containing ten herbs that has been found to be beneficial in open studies was tested in a double-blind placebo-controlled study. 40 adult patients with longstanding, refractory, widespread, atopic dermatitis were randomised into two groups to receive 2 months' treatment of either the active formulation of herbs (TCHT) or placebo herbs, followed by a crossover to the other treatment after a 4-week washout period. The main outcome measures were extent and severity of erythema and surface damage as judged by standardised body scores. The patients' own assessments of the overall response to treatment were also sought. The geometric mean score for erythema at the end of active treatment was 12.6 (95% confidence interval [CI] 5.9 to 22.0) and at the end of the placebo phase was 113 (65 to 180). The geometric mean score for surface damage was 11.3 (5.8 to 21.8) and 111.0 (68 to 182), respectively. The 95% CI for the mean geometric ratio for the two values with active treatment was 0.04 to 0.22 for erythema (p less than 0.0005) and 0.04 to 0.27 for surface damage (p less than 0.0005). Of the 31 patients who completed the study and expressed a preference, 20 preferred that phase of the trial in which they received TCHT whereas 4 patients preferred placebo (p less than 0.02). There was a subjective improvement in itching (p less than 0.001) and sleep (p less than 0.078) during the TCHT treatment phase. No side-effects were reported by the patients although many commented on the unpalatability of the decoction. TCHT seems to benefit patients with atopic dermatitis. Palatability of the treatment needs to be improved and its safety assured.
A Y Fung, P C Look, L Y Chong, P P But, E Wong
A controlled trial of traditional Chinese herbal medicine in Chinese patients with recalcitrant atopic dermatitis.
Int J Dermatol. 1999 May;38(5):387-92.
Abstract/Text
BACKGROUND: There have been published reports from the United Kingdom of good responses to the use of traditional Chinese herbal medicine (Zemaphyte, Phytopharm Plc, Cambridge, UK) in treating recalcitrant atopic dermatitis. We conducted a double-blind, placebo-controlled, cross-over study among Chinese patients with recalcitrant atopic dermatitis using this same herbal preparation.
METHODS: Forty patients were recruited. They were given Zemaphyte and placebo in random order, each for 8 consecutive weeks with a 4-week wash-out period in between. Scores based on the severity and extent of four clinical parameters (erythema, surface damage, lichenification and scaling) were recorded at baseline and at 4-weekly intervals throughout the 20-week trial period.
RESULTS: Thirty-seven patients completed the trial. There was a general trend of clinical improvement with time throughout the trial period in both patient groups, irrespective of whether they received Zemaphyte or placebo first. Zemaphyte, however, offered no statistically significant treatment effect over placebo for all four clinical parameters, except for lichenification at week 4. There were no significant carry-over effects. Blood tests for hematologic, renal and liver functions were all normal throughout the trial.
CONCLUSIONS: Zemaphyte did not seem to benefit Chinese patients with recalcitrant atopic dermatitis in our study. Further research is required to evaluate its efficacy.
A Y Fung, P C Look, L Y Chong, P P But, E Wong
A controlled trial of traditional Chinese herbal medicine in Chinese patients with recalcitrant atopic dermatitis.
Int J Dermatol. 1999 May;38(5):387-92.
Abstract/Text
BACKGROUND: There have been published reports from the United Kingdom of good responses to the use of traditional Chinese herbal medicine (Zemaphyte, Phytopharm Plc, Cambridge, UK) in treating recalcitrant atopic dermatitis. We conducted a double-blind, placebo-controlled, cross-over study among Chinese patients with recalcitrant atopic dermatitis using this same herbal preparation.
METHODS: Forty patients were recruited. They were given Zemaphyte and placebo in random order, each for 8 consecutive weeks with a 4-week wash-out period in between. Scores based on the severity and extent of four clinical parameters (erythema, surface damage, lichenification and scaling) were recorded at baseline and at 4-weekly intervals throughout the 20-week trial period.
RESULTS: Thirty-seven patients completed the trial. There was a general trend of clinical improvement with time throughout the trial period in both patient groups, irrespective of whether they received Zemaphyte or placebo first. Zemaphyte, however, offered no statistically significant treatment effect over placebo for all four clinical parameters, except for lichenification at week 4. There were no significant carry-over effects. Blood tests for hematologic, renal and liver functions were all normal throughout the trial.
CONCLUSIONS: Zemaphyte did not seem to benefit Chinese patients with recalcitrant atopic dermatitis in our study. Further research is required to evaluate its efficacy.
F Bath-Hextall, F M Delamere, H C Williams
Dietary exclusions for improving established atopic eczema in adults and children: systematic review.
Allergy. 2009 Feb;64(2):258-64. doi: 10.1111/j.1398-9995.2008.01917.x.
Abstract/Text
Atopic eczema is the most common inflammatory skin disease of childhood in developed countries. We performed a systematic review of randomized controlled trials to assess the effects of dietary exclusions for the treatment of established atopic eczema. Nine trials (421 participants) were included, most of which were poorly reported. Six were studies of egg and milk exclusion (n = 288), one was a study of few foods (n = 85) and two were studies of an elemental diet (n = 48). There appears to be no benefit of an egg- and milk-free diet in unselected participants with atopic eczema. There is also no evidence of benefit in the use of an elemental or few-foods diet in unselected cases of atopic eczema. There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs - one study found 51% of the children had a significant improvement in body surface area with the exclusion diet as compared with normal diet (95% CI 1.07-2.11) and change in surface area and severity score was significantly improved in the exclusion diet as compared with the normal diet at the end of 6 weeks (MD 5.50, 95% CI 0.19-10.81) and end of treatment (MD 6.10, 95% CI 0.06-12.14). Despite their frequent use, we find little good quality evidence to support the use of exclusion diets in atopic eczema.
F Bath-Hextall, F M Delamere, H C Williams
Dietary exclusions for improving established atopic eczema in adults and children: systematic review.
Allergy. 2009 Feb;64(2):258-64. doi: 10.1111/j.1398-9995.2008.01917.x.
Abstract/Text
Atopic eczema is the most common inflammatory skin disease of childhood in developed countries. We performed a systematic review of randomized controlled trials to assess the effects of dietary exclusions for the treatment of established atopic eczema. Nine trials (421 participants) were included, most of which were poorly reported. Six were studies of egg and milk exclusion (n = 288), one was a study of few foods (n = 85) and two were studies of an elemental diet (n = 48). There appears to be no benefit of an egg- and milk-free diet in unselected participants with atopic eczema. There is also no evidence of benefit in the use of an elemental or few-foods diet in unselected cases of atopic eczema. There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs - one study found 51% of the children had a significant improvement in body surface area with the exclusion diet as compared with normal diet (95% CI 1.07-2.11) and change in surface area and severity score was significantly improved in the exclusion diet as compared with the normal diet at the end of 6 weeks (MD 5.50, 95% CI 0.19-10.81) and end of treatment (MD 6.10, 95% CI 0.06-12.14). Despite their frequent use, we find little good quality evidence to support the use of exclusion diets in atopic eczema.
[https://www.foodallergy.jp/wp-content/themes/foodallergy/pdf/manual2020.pdf 食物アレルギーの診療の手引き2020、p13.
[https://www.foodallergy.jp/wp-content/themes/foodallergy/pdf/manual2020.pdf 食物アレルギーの診療の手引き2020、p13.
Gideon Lack, Deborah Fox, Kate Northstone, Jean Golding, Avon Longitudinal Study of Parents and Children Study Team
Factors associated with the development of peanut allergy in childhood.
N Engl J Med. 2003 Mar 13;348(11):977-85. doi: 10.1056/NEJMoa013536. Epub 2003 Mar 10.
Abstract/Text
BACKGROUND: The prevalence of peanut allergy appears to have increased in recent decades. Other than a family history of peanut allergy and the presence of atopy, there are no known risk factors.
METHODS: We used data from the Avon Longitudinal Study of Parents and Children, a geographically defined cohort study of 13,971 preschool children, to identify those with a convincing history of peanut allergy and the subgroup that reacted to a double-blind peanut challenge. We first prospectively collected data on the whole cohort and then collected detailed information retrospectively by interview from the parents of children with peanut reactions and of children from two groups of controls (a random sample from the cohort and a group of children whose mothers had a history of eczema and who had had eczema themselves in the first six months of life).
RESULTS: Forty-nine children had a history of peanut allergy; peanut allergy was confirmed by peanut challenge in 23 of 36 children tested. There was no evidence of prenatal sensitization from the maternal diet, and peanut-specific IgE was not detectable in the cord blood. Peanut allergy was independently associated with intake of soy milk or soy formula (odds ratio, 2.6; 95 percent confidence interval, 1.3 to 5.2), rash over joints and skin creases (odds ratio, 2.6; 95 percent confidence interval, 1.4 to 5.0), and oozing, crusted rash (odds ratio, 5.2; 95 percent confidence interval, 2.7 to 10.2). Analysis of interview data showed a significant independent relation of peanut allergy with the use of skin preparations containing peanut oil (odds ratio, 6.8; 95 percent confidence interval, 1.4 to 32.9).
CONCLUSIONS: Sensitization to peanut protein may occur in children through the application of peanut oil to inflamed skin. The association with soy protein could arise from cross-sensitization through common epitopes. Confirmation of these risk factors in future studies could lead to new strategies to prevent sensitization in infants who are at risk for subsequent peanut allergy.
Copyright 2003 Massachusetts Medical Society
Gideon Lack, Deborah Fox, Kate Northstone, Jean Golding, Avon Longitudinal Study of Parents and Children Study Team
Factors associated with the development of peanut allergy in childhood.
N Engl J Med. 2003 Mar 13;348(11):977-85. doi: 10.1056/NEJMoa013536. Epub 2003 Mar 10.
Abstract/Text
BACKGROUND: The prevalence of peanut allergy appears to have increased in recent decades. Other than a family history of peanut allergy and the presence of atopy, there are no known risk factors.
METHODS: We used data from the Avon Longitudinal Study of Parents and Children, a geographically defined cohort study of 13,971 preschool children, to identify those with a convincing history of peanut allergy and the subgroup that reacted to a double-blind peanut challenge. We first prospectively collected data on the whole cohort and then collected detailed information retrospectively by interview from the parents of children with peanut reactions and of children from two groups of controls (a random sample from the cohort and a group of children whose mothers had a history of eczema and who had had eczema themselves in the first six months of life).
RESULTS: Forty-nine children had a history of peanut allergy; peanut allergy was confirmed by peanut challenge in 23 of 36 children tested. There was no evidence of prenatal sensitization from the maternal diet, and peanut-specific IgE was not detectable in the cord blood. Peanut allergy was independently associated with intake of soy milk or soy formula (odds ratio, 2.6; 95 percent confidence interval, 1.3 to 5.2), rash over joints and skin creases (odds ratio, 2.6; 95 percent confidence interval, 1.4 to 5.0), and oozing, crusted rash (odds ratio, 5.2; 95 percent confidence interval, 2.7 to 10.2). Analysis of interview data showed a significant independent relation of peanut allergy with the use of skin preparations containing peanut oil (odds ratio, 6.8; 95 percent confidence interval, 1.4 to 32.9).
CONCLUSIONS: Sensitization to peanut protein may occur in children through the application of peanut oil to inflamed skin. The association with soy protein could arise from cross-sensitization through common epitopes. Confirmation of these risk factors in future studies could lead to new strategies to prevent sensitization in infants who are at risk for subsequent peanut allergy.
Copyright 2003 Massachusetts Medical Society
Helen A Brough, Angela Simpson, Kerry Makinson, Jenny Hankinson, Sara Brown, Abdel Douiri, Danielle C M Belgrave, Martin Penagos, Alick C Stephens, W H Irwin McLean, Victor Turcanu, Nicolaos Nicolaou, Adnan Custovic, Gideon Lack
Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations.
J Allergy Clin Immunol. 2014 Oct;134(4):867-875.e1. doi: 10.1016/j.jaci.2014.08.011.
Abstract/Text
BACKGROUND: Filaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption.
OBJECTIVE: We sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds.
METHODS: Exposure to peanut antigen in dust within the first year of life was measured in a population-based birth cohort. Peanut sensitization and peanut allergy (defined by using oral food challenges or component-resolved diagnostics [CRD]) were assessed at 8 and 11 years. Genotyping was performed for 6 FLG mutations.
RESULTS: After adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanut dust levels and FLG mutations on peanut sensitization and peanut allergy. Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a more than 6-fold increased odds of peanut SPT sensitization, CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG. There was no significant effect of exposure in children without FLG mutations. In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 0.92 μg of peanut protein per gram (95% CI, 0.70-1.22 μg/g), that for CRD sensitization was 1.03 μg/g (95% CI, 0.90-1.82 μg/g), and that for peanut allergy was 1.17 μg/g (95% CI, 0.01-163.83 μg/g).
CONCLUSION: Early-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation. These data support the hypothesis that peanut allergy develops through transcutaneous sensitization in children with an impaired skin barrier.
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Helen A Brough, Angela Simpson, Kerry Makinson, Jenny Hankinson, Sara Brown, Abdel Douiri, Danielle C M Belgrave, Martin Penagos, Alick C Stephens, W H Irwin McLean, Victor Turcanu, Nicolaos Nicolaou, Adnan Custovic, Gideon Lack
Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations.
J Allergy Clin Immunol. 2014 Oct;134(4):867-875.e1. doi: 10.1016/j.jaci.2014.08.011.
Abstract/Text
BACKGROUND: Filaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption.
OBJECTIVE: We sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds.
METHODS: Exposure to peanut antigen in dust within the first year of life was measured in a population-based birth cohort. Peanut sensitization and peanut allergy (defined by using oral food challenges or component-resolved diagnostics [CRD]) were assessed at 8 and 11 years. Genotyping was performed for 6 FLG mutations.
RESULTS: After adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanut dust levels and FLG mutations on peanut sensitization and peanut allergy. Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a more than 6-fold increased odds of peanut SPT sensitization, CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG. There was no significant effect of exposure in children without FLG mutations. In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 0.92 μg of peanut protein per gram (95% CI, 0.70-1.22 μg/g), that for CRD sensitization was 1.03 μg/g (95% CI, 0.90-1.82 μg/g), and that for peanut allergy was 1.17 μg/g (95% CI, 0.01-163.83 μg/g).
CONCLUSION: Early-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation. These data support the hypothesis that peanut allergy develops through transcutaneous sensitization in children with an impaired skin barrier.
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Helen A Brough, Andrew H Liu, Scott Sicherer, Kerry Makinson, Abdel Douiri, Sara J Brown, Alick C Stephens, W H Irwin McLean, Victor Turcanu, Robert A Wood, Stacie M Jones, Wesley Burks, Peter Dawson, Donald Stablein, Hugh Sampson, Gideon Lack
Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy.
J Allergy Clin Immunol. 2015 Jan;135(1):164-70. doi: 10.1016/j.jaci.2014.10.007. Epub 2014 Nov 18.
Abstract/Text
BACKGROUND: History and severity of atopic dermatitis (AD) are risk factors for peanut allergy. Recent evidence suggests that children can become sensitized to food allergens through an impaired skin barrier. Household peanut consumption, which correlates strongly with peanut protein levels in household dust, is a risk factor for peanut allergy.
OBJECTIVE: We sought to assess whether environmental peanut exposure (EPE) is a risk for peanut sensitization and allergy and whether markers of an impaired skin barrier modify this risk.
METHODS: Peanut protein in household dust (in micrograms per gram) was assessed in highly atopic children (age, 3-15 months) recruited to the Consortium of Food Allergy Research Observational Study. History and severity of AD, peanut sensitization, and likely allergy (peanut-specific IgE, ≥5 kUA/mL) were assessed at recruitment into the Consortium of Food Allergy Research study.
RESULTS: There was an exposure-response relationship between peanut protein levels in household dust and peanut skin prick test (SPT) sensitization and likely allergy. In the final multivariate model an increase in 4 log2 EPE units increased the odds of peanut SPT sensitization (1.71-fold; 95% CI, 1.13- to 2.59-fold; P = .01) and likely peanut allergy (PA; 2.10-fold; 95% CI, 1.20- to 3.67-fold; P < .01). The effect of EPE on peanut SPT sensitization was augmented in children with a history of AD (OR, 1.97; 95% CI, 1.26-3.09; P < .01) and augmented even further in children with a history of severe AD (OR, 2.41; 95% CI, 1.30-4.47; P < .01); the effect of EPE on PA was also augmented in children with a history of AD (OR, 2.34; 95% CI, 1.31-4.18; P < .01).
CONCLUSION: Exposure to peanut antigen in dust through an impaired skin barrier in atopically inflamed skin is a plausible route for peanut SPT sensitization and PA.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Helen A Brough, Andrew H Liu, Scott Sicherer, Kerry Makinson, Abdel Douiri, Sara J Brown, Alick C Stephens, W H Irwin McLean, Victor Turcanu, Robert A Wood, Stacie M Jones, Wesley Burks, Peter Dawson, Donald Stablein, Hugh Sampson, Gideon Lack
Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy.
J Allergy Clin Immunol. 2015 Jan;135(1):164-70. doi: 10.1016/j.jaci.2014.10.007. Epub 2014 Nov 18.
Abstract/Text
BACKGROUND: History and severity of atopic dermatitis (AD) are risk factors for peanut allergy. Recent evidence suggests that children can become sensitized to food allergens through an impaired skin barrier. Household peanut consumption, which correlates strongly with peanut protein levels in household dust, is a risk factor for peanut allergy.
OBJECTIVE: We sought to assess whether environmental peanut exposure (EPE) is a risk for peanut sensitization and allergy and whether markers of an impaired skin barrier modify this risk.
METHODS: Peanut protein in household dust (in micrograms per gram) was assessed in highly atopic children (age, 3-15 months) recruited to the Consortium of Food Allergy Research Observational Study. History and severity of AD, peanut sensitization, and likely allergy (peanut-specific IgE, ≥5 kUA/mL) were assessed at recruitment into the Consortium of Food Allergy Research study.
RESULTS: There was an exposure-response relationship between peanut protein levels in household dust and peanut skin prick test (SPT) sensitization and likely allergy. In the final multivariate model an increase in 4 log2 EPE units increased the odds of peanut SPT sensitization (1.71-fold; 95% CI, 1.13- to 2.59-fold; P = .01) and likely peanut allergy (PA; 2.10-fold; 95% CI, 1.20- to 3.67-fold; P < .01). The effect of EPE on peanut SPT sensitization was augmented in children with a history of AD (OR, 1.97; 95% CI, 1.26-3.09; P < .01) and augmented even further in children with a history of severe AD (OR, 2.41; 95% CI, 1.30-4.47; P < .01); the effect of EPE on PA was also augmented in children with a history of AD (OR, 2.34; 95% CI, 1.31-4.18; P < .01).
CONCLUSION: Exposure to peanut antigen in dust through an impaired skin barrier in atopically inflamed skin is a plausible route for peanut SPT sensitization and PA.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
G Ricci, A Patrizi, F Specchia, L Menna, P Bottau, V D'Angelo, M Masi
Effect of house dust mite avoidance measures in children with atopic dermatitis.
Br J Dermatol. 2000 Aug;143(2):379-84.
Abstract/Text
BACKGROUND: House dust mite allergens are associated with atopic dermatitis (AD).
OBJECTIVES: The aim of our study was to verify if house dust mite allergen avoidance measures can improve the clinical manifestations of AD in children.
METHODS: Forty-one children (mean age 3.9 years) affected by AD associated with high total and/or specific IgE serum levels ('extrinsic' AD) were recruited. Clinical evaluation was performed utilizing the Severity Scoring of AD (SCORAD) index; dust was sampled from the children's beds and tested using an enzyme-linked immunosorbent assay. The study was planned in two parts. In the first part, a placebo-controlled trial of 2 months duration, mite allergen avoidance measures (encasing mattresses and pillows; a weekly hot wash of bedding; frequent vacuum cleaning of living room and bedroom; soft toys and carpets regularly cleaned or removed; no pets allowed) were recommended to group A patients, but not to group B. In the second part of the study, environmental avoidance measures were recommended to initial control group B patients also. One year after the start of the study the amounts of mite allergen in the home and clinical score of AD were measured in both groups.
RESULTS: At the end of the first part of the study, significant decreases in major allergens of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) load (from 393 to 94 ng m-2) and concentration (from 1.84 to 0.73 microg g-1 of dust) in children's beds were observed in treatment group A. At the same time, in this group the mean SCORAD index improved significantly (from 33 to 26; P = 0.022). After 12 months, when all patients had used allergen avoidance measures, Der p1 + Der f1 load, concentration and clinical score had improved, reaching similar values in both groups.
CONCLUSIONS: Simple mite allergen avoidance measures should be recommended to families with children affected by extrinsic AD in order to control the clinical manifestations and prevent mite sensitization.
G Ricci, A Patrizi, F Specchia, L Menna, P Bottau, V D'Angelo, M Masi
Effect of house dust mite avoidance measures in children with atopic dermatitis.
Br J Dermatol. 2000 Aug;143(2):379-84.
Abstract/Text
BACKGROUND: House dust mite allergens are associated with atopic dermatitis (AD).
OBJECTIVES: The aim of our study was to verify if house dust mite allergen avoidance measures can improve the clinical manifestations of AD in children.
METHODS: Forty-one children (mean age 3.9 years) affected by AD associated with high total and/or specific IgE serum levels ('extrinsic' AD) were recruited. Clinical evaluation was performed utilizing the Severity Scoring of AD (SCORAD) index; dust was sampled from the children's beds and tested using an enzyme-linked immunosorbent assay. The study was planned in two parts. In the first part, a placebo-controlled trial of 2 months duration, mite allergen avoidance measures (encasing mattresses and pillows; a weekly hot wash of bedding; frequent vacuum cleaning of living room and bedroom; soft toys and carpets regularly cleaned or removed; no pets allowed) were recommended to group A patients, but not to group B. In the second part of the study, environmental avoidance measures were recommended to initial control group B patients also. One year after the start of the study the amounts of mite allergen in the home and clinical score of AD were measured in both groups.
RESULTS: At the end of the first part of the study, significant decreases in major allergens of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) load (from 393 to 94 ng m-2) and concentration (from 1.84 to 0.73 microg g-1 of dust) in children's beds were observed in treatment group A. At the same time, in this group the mean SCORAD index improved significantly (from 33 to 26; P = 0.022). After 12 months, when all patients had used allergen avoidance measures, Der p1 + Der f1 load, concentration and clinical score had improved, reaching similar values in both groups.
CONCLUSIONS: Simple mite allergen avoidance measures should be recommended to families with children affected by extrinsic AD in order to control the clinical manifestations and prevent mite sensitization.
C Gutgesell, S Heise, S Seubert, A Seubert, S Domhof, E Brunner, C Neumann
Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitis.
Br J Dermatol. 2001 Jul;145(1):70-4.
Abstract/Text
BACKGROUND: Avoidance of allergens has been shown to be of benefit in patients with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is so far little information about the effect of house dust mite elimination strategies.
OBJECTIVES: We therefore performed a randomized controlled study of house dust mite control in patients with this disease.
METHODS: Twenty adult patients with moderate to severe atopic dermatitis were included. Inclusion criteria were a positive RAST to house dust mite antigen (CAP class > 3) and a concentration of > 2 microg g(-1) of the house dust mite antigen Der p1 in the patient's mattress dust. Patients were randomized to either the active treatment group (allergen-impermeable mattress encasing, acaricide spray containing tannic acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray containing water and traces of ethanol). Severity of disease was estimated every 2 months by an established score (SCORAD), and eosinophil cationic protein (ECP) in the serum was determined by enzyme-linked immunosorbent assay. Furthermore, the use of topical steroids was quantified. Patients assessed daytime pruritus and pruritus-induced sleeplessness weekly on a visual analogue scale. The study lasted 1 year.
RESULTS: At the end of the study, the active treatment group showed a statistically significant reduction in Der p1 exposure as compared with the control group. However, when comparing the change from the start to the end of the study, there was no statistically significant difference between active treatment and control groups as measured by the SCORAD score and by ECP levels in the serum. Some patients in the active treatment group reported less pruritus-induced sleeplessness, but there was no statistically significant difference between the two treatment groups.
CONCLUSIONS: For adult patients with atopic dermatitis it was shown that 1 year of house dust mite avoidance reduced the allergen exposure, but an improvement of overall disease activity was not demonstrated.
C Gutgesell, S Heise, S Seubert, A Seubert, S Domhof, E Brunner, C Neumann
Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitis.
Br J Dermatol. 2001 Jul;145(1):70-4.
Abstract/Text
BACKGROUND: Avoidance of allergens has been shown to be of benefit in patients with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is so far little information about the effect of house dust mite elimination strategies.
OBJECTIVES: We therefore performed a randomized controlled study of house dust mite control in patients with this disease.
METHODS: Twenty adult patients with moderate to severe atopic dermatitis were included. Inclusion criteria were a positive RAST to house dust mite antigen (CAP class > 3) and a concentration of > 2 microg g(-1) of the house dust mite antigen Der p1 in the patient's mattress dust. Patients were randomized to either the active treatment group (allergen-impermeable mattress encasing, acaricide spray containing tannic acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray containing water and traces of ethanol). Severity of disease was estimated every 2 months by an established score (SCORAD), and eosinophil cationic protein (ECP) in the serum was determined by enzyme-linked immunosorbent assay. Furthermore, the use of topical steroids was quantified. Patients assessed daytime pruritus and pruritus-induced sleeplessness weekly on a visual analogue scale. The study lasted 1 year.
RESULTS: At the end of the study, the active treatment group showed a statistically significant reduction in Der p1 exposure as compared with the control group. However, when comparing the change from the start to the end of the study, there was no statistically significant difference between active treatment and control groups as measured by the SCORAD score and by ECP levels in the serum. Some patients in the active treatment group reported less pruritus-induced sleeplessness, but there was no statistically significant difference between the two treatment groups.
CONCLUSIONS: For adult patients with atopic dermatitis it was shown that 1 year of house dust mite avoidance reduced the allergen exposure, but an improvement of overall disease activity was not demonstrated.
Eric L Simpson, Thomas Bieber, Emma Guttman-Yassky, Lisa A Beck, Andrew Blauvelt, Michael J Cork, Jonathan I Silverberg, Mette Deleuran, Yoko Kataoka, Jean-Philippe Lacour, Külli Kingo, Margitta Worm, Yves Poulin, Andreas Wollenberg, Yuhwen Soo, Neil M H Graham, Gianluca Pirozzi, Bolanle Akinlade, Heribert Staudinger, Vera Mastey, Laurent Eckert, Abhijit Gadkari, Neil Stahl, George D Yancopoulos, Marius Ardeleanu, SOLO 1 and SOLO 2 Investigators
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.
N Engl J Med. 2016 Dec 15;375(24):2335-2348. doi: 10.1056/NEJMoa1610020. Epub 2016 Sep 30.
Abstract/Text
BACKGROUND: Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.
METHODS: In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16.
RESULTS: We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups.
CONCLUSIONS: In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).
Eric L Simpson, Thomas Bieber, Emma Guttman-Yassky, Lisa A Beck, Andrew Blauvelt, Michael J Cork, Jonathan I Silverberg, Mette Deleuran, Yoko Kataoka, Jean-Philippe Lacour, Külli Kingo, Margitta Worm, Yves Poulin, Andreas Wollenberg, Yuhwen Soo, Neil M H Graham, Gianluca Pirozzi, Bolanle Akinlade, Heribert Staudinger, Vera Mastey, Laurent Eckert, Abhijit Gadkari, Neil Stahl, George D Yancopoulos, Marius Ardeleanu, SOLO 1 and SOLO 2 Investigators
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.
N Engl J Med. 2016 Dec 15;375(24):2335-2348. doi: 10.1056/NEJMoa1610020. Epub 2016 Sep 30.
Abstract/Text
BACKGROUND: Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.
METHODS: In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16.
RESULTS: We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups.
CONCLUSIONS: In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).
Eric L Simpson, Amy S Paller, Elaine C Siegfried, Mark Boguniewicz, Lawrence Sher, Melinda J Gooderham, Lisa A Beck, Emma Guttman-Yassky, David Pariser, Andrew Blauvelt, Jamie Weisman, Benjamin Lockshin, Thomas Hultsch, Qin Zhang, Mohamed A Kamal, John D Davis, Bolanle Akinlade, Heribert Staudinger, Jennifer D Hamilton, Neil M H Graham, Gianluca Pirozzi, Abhijit Gadkari, Laurent Eckert, Neil Stahl, George D Yancopoulos, Marcella Ruddy, Ashish Bansal
Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial.
JAMA Dermatol. 2020 Jan 1;156(1):44-56. doi: 10.1001/jamadermatol.2019.3336.
Abstract/Text
IMPORTANCE: Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, with limited treatment options. The efficacy and safety of dupilumab, a monoclonal antibody, approved for treatment in adolescent patients with inadequately controlled AD, remain unknown in this patient population.
OBJECTIVE: To assess the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled AD.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, parallel-group, phase 3 clinical trial was conducted at 45 US and Canadian centers between March 21, 2017, and June 5, 2018. A total of 251 adolescents with moderate to severe AD inadequately controlled by topical medications or for whom topical therapy was inadvisable were included.
INTERVENTIONS: Patients were randomized (1:1:1; interactive-response system; stratified by severity and body weight) to 16-week treatment with dupilumab, 200 mg (n = 43; baseline weight <60 kg), or dupilumab, 300 mg (n = 39; baseline weight ≥60 kg), every 2 weeks; dupilumab, 300 mg, every 4 weeks (n = 84); or placebo (n = 85).
MAIN OUTCOMES AND MEASURES: Proportion of patients with 75% or more improvement from baseline in Eczema Area and Severity Index (EASI-75) (scores range from 0 to 72, with higher scores indicating greater severity) and Investigator's Global Assessment (IGA) 0 or 1 on a 5-point scale (scores range from 0 to 4, with higher scores indicating greater severity) at week 16.
RESULTS: A total of 251 patients were randomized (mean [SD] age, 14.5 [1.7] years; 148 [59.0%] male). Of 250 patients with data available on concurrent allergic conditions, most had comorbid type 2 diseases (asthma, 134 [53.6%]; food allergies, 60.8%; allergic rhinitis, 65.6%). A total of 240 patients (95.6%) completed the study. Dupilumab achieved both coprimary end points at week 16. The proportion of patients with EASI-75 improvement from baseline increased (every 2 weeks, 41.5%; every 4 weeks, 38.1%; placebo, 8.2%) with differences vs placebo of 33.2% (95% CI, 21.1%-45.4%) for every 2 weeks and 29.9% (95% CI, 17.9%-41.8%) for every 4 weeks (P < .001). Efficacy of the every-2-week regimen was generally superior to the every-4-week regimen. Patients in the dupilumab arms had higher percentage values of conjunctivitis (every 2 weeks, 9.8%; every 4 weeks, 10.8%; placebo, 4.7%) and injection-site reactions (every 2 weeks, 8.5%; every 4 weeks, 6.0%; placebo, 3.5%), and lower nonherpetic skin infections (every 2 weeks, 9.8%; every 4 weeks, 9.6%; placebo, 18.8%).
CONCLUSIONS AND RELEVANCE: In this study, dupilumab significantly improved AD signs, symptoms, and quality of life in adolescents with moderate to severe AD, with an acceptable safety profile. Placebo-corrected efficacy and safety of dupilumab were similar in adolescents and adults.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03054428.
Amy S Paller, Elaine C Siegfried, Diamant Thaçi, Andreas Wollenberg, Michael J Cork, Peter D Arkwright, Melinda Gooderham, Lisa A Beck, Mark Boguniewicz, Lawrence Sher, Jamie Weisman, John T O'Malley, Naimish Patel, Megan Hardin, Neil M H Graham, Marcella Ruddy, Xian Sun, John D Davis, Mohamed A Kamal, Faisal A Khokhar, David M Weinreich, George D Yancopoulos, Bethany Beazley, Ashish Bansal, Brad Shumel
Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial.
J Am Acad Dermatol. 2020 Nov;83(5):1282-1293. doi: 10.1016/j.jaad.2020.06.054. Epub 2020 Jun 20.
Abstract/Text
BACKGROUND: Children with severe atopic dermatitis (AD) have limited treatment options.
OBJECTIVE: We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies.
METHODS: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS.
RESULTS: Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS.
LIMITATIONS: Short-term 16-week treatment period; severe AD only.
CONCLUSION: Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL.
Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Amy S Paller, Elaine C Siegfried, Diamant Thaçi, Andreas Wollenberg, Michael J Cork, Peter D Arkwright, Melinda Gooderham, Lisa A Beck, Mark Boguniewicz, Lawrence Sher, Jamie Weisman, John T O'Malley, Naimish Patel, Megan Hardin, Neil M H Graham, Marcella Ruddy, Xian Sun, John D Davis, Mohamed A Kamal, Faisal A Khokhar, David M Weinreich, George D Yancopoulos, Bethany Beazley, Ashish Bansal, Brad Shumel
Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial.
J Am Acad Dermatol. 2020 Nov;83(5):1282-1293. doi: 10.1016/j.jaad.2020.06.054. Epub 2020 Jun 20.
Abstract/Text
BACKGROUND: Children with severe atopic dermatitis (AD) have limited treatment options.
OBJECTIVE: We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years with severe AD inadequately controlled with topical therapies.
METHODS: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS.
RESULTS: Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator's Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS.
LIMITATIONS: Short-term 16-week treatment period; severe AD only.
CONCLUSION: Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL.
Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Amy S Paller, Eric L Simpson, Elaine C Siegfried, Michael J Cork, Andreas Wollenberg, Peter D Arkwright, Weily Soong, Mercedes E Gonzalez, Lynda C Schneider, Robert Sidbury, Benjamin Lockshin, Steven Meltzer, Zhixiao Wang, Leda P Mannent, Nikhil Amin, Yiping Sun, Elizabeth Laws, Bolanle Akinlade, Myles Dillon, Matthew P Kosloski, Mohamed A Kamal, Ariane Dubost-Brama, Naimish Patel, David M Weinreich, George D Yancopoulos, John T O'Malley, Ashish Bansal, participating investigators
Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet. 2022 Sep 17;400(10356):908-919. doi: 10.1016/S0140-6736(22)01539-2.
Abstract/Text
BACKGROUND: Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis.
METHODS: This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434.
FINDINGS: Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation.
INTERPRETATION: Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults.
FUNDING: Sanofi and Regeneron Pharmaceuticals.
Copyright © 2022 Elsevier Ltd. All rights reserved.
Amy S Paller, Eric L Simpson, Elaine C Siegfried, Michael J Cork, Andreas Wollenberg, Peter D Arkwright, Weily Soong, Mercedes E Gonzalez, Lynda C Schneider, Robert Sidbury, Benjamin Lockshin, Steven Meltzer, Zhixiao Wang, Leda P Mannent, Nikhil Amin, Yiping Sun, Elizabeth Laws, Bolanle Akinlade, Myles Dillon, Matthew P Kosloski, Mohamed A Kamal, Ariane Dubost-Brama, Naimish Patel, David M Weinreich, George D Yancopoulos, John T O'Malley, Ashish Bansal, participating investigators
Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet. 2022 Sep 17;400(10356):908-919. doi: 10.1016/S0140-6736(22)01539-2.
Abstract/Text
BACKGROUND: Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis.
METHODS: This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434.
FINDINGS: Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation.
INTERPRETATION: Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults.
FUNDING: Sanofi and Regeneron Pharmaceuticals.
Copyright © 2022 Elsevier Ltd. All rights reserved.
A Wollenberg, A Blauvelt, E Guttman-Yassky, M Worm, C Lynde, J-P Lacour, L Spelman, N Katoh, H Saeki, Y Poulin, A Lesiak, L Kircik, S H Cho, P Herranz, M J Cork, K Peris, L A Steffensen, B Bang, A Kuznetsova, T N Jensen, M L Østerdal, E L Simpson, ECZTRA 1 and ECZTRA 2 study investigators
Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).
Br J Dermatol. 2021 Mar;184(3):437-449. doi: 10.1111/bjd.19574. Epub 2020 Dec 30.
Abstract/Text
BACKGROUND: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms.
OBJECTIVES: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments.
METHODS: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885.
RESULTS: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period.
CONCLUSIONS: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.
© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
A Wollenberg, A Blauvelt, E Guttman-Yassky, M Worm, C Lynde, J-P Lacour, L Spelman, N Katoh, H Saeki, Y Poulin, A Lesiak, L Kircik, S H Cho, P Herranz, M J Cork, K Peris, L A Steffensen, B Bang, A Kuznetsova, T N Jensen, M L Østerdal, E L Simpson, ECZTRA 1 and ECZTRA 2 study investigators
Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).
Br J Dermatol. 2021 Mar;184(3):437-449. doi: 10.1111/bjd.19574. Epub 2020 Dec 30.
Abstract/Text
BACKGROUND: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms.
OBJECTIVES: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments.
METHODS: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885.
RESULTS: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period.
CONCLUSIONS: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.
© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
K Kabashima, T Matsumura, H Komazaki, M Kawashima, Nemolizumab JP01 andJP02 Study Group
Nemolizumab plus topical agents in patients with atopic dermatitis (AD) and moderate-to-severe pruritus provide improvement in pruritus and signs of AD for up to 68 weeks: results from two phase III, long-term studies.
Br J Dermatol. 2022 Apr;186(4):642-651. doi: 10.1111/bjd.20873. Epub 2021 Dec 21.
Abstract/Text
BACKGROUND: Interleukin (IL)-31 affects the inflammatory response, is involved in epidermal barrier disruption in atopic dermatitis (AD) and plays a key role in pruritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administration period.
OBJECTIVES: To examine the long-term effectiveness and safety of nemolizumab in patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus.
METHODS: In two long-term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concomitantly with topical treatments. Study-JP01 patients received double-blind nemolizumab or placebo for 16 weeks, and then entered a 52-week extension period in which all patients received nemolizumab (nemolizumab/nemolizumab and placebo/nemolizumab groups). Study-JP02 patients received nemolizumab for 52 weeks. Both studies included an 8-week follow-up period.
RESULTS: Study-JP01 nemolizumab/nemolizumab and placebo/nemolizumab, and Study-JP02 nemolizumab groups comprised 143, 72 and 88 patients, respectively. In the nemolizumab/nemolizumab group, there were clinically meaningful improvements from the start of treatment to week 68 in the pruritus visual analogue scale (66% decrease) and Eczema Area and Severity Index (78% decrease). Quality of life (QoL) indicators improved after the first nemolizumab dose; improvements were maintained during the follow-up period. The long-term safety profile was consistent with previous studies, with no unexpected late-onset adverse events.
CONCLUSIONS: Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate-to-severe pruritus produced a continuous improvement in pruritus, signs of AD, and QoL for up to 68 weeks, with a favourable safety profile.
© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
K Kabashima, T Matsumura, H Komazaki, M Kawashima, Nemolizumab JP01 andJP02 Study Group
Nemolizumab plus topical agents in patients with atopic dermatitis (AD) and moderate-to-severe pruritus provide improvement in pruritus and signs of AD for up to 68 weeks: results from two phase III, long-term studies.
Br J Dermatol. 2022 Apr;186(4):642-651. doi: 10.1111/bjd.20873. Epub 2021 Dec 21.
Abstract/Text
BACKGROUND: Interleukin (IL)-31 affects the inflammatory response, is involved in epidermal barrier disruption in atopic dermatitis (AD) and plays a key role in pruritus. Nemolizumab, a humanized monoclonal antibody against IL-31 receptor A, reduced pruritus in patients with AD after a 16-week administration period.
OBJECTIVES: To examine the long-term effectiveness and safety of nemolizumab in patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus.
METHODS: In two long-term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concomitantly with topical treatments. Study-JP01 patients received double-blind nemolizumab or placebo for 16 weeks, and then entered a 52-week extension period in which all patients received nemolizumab (nemolizumab/nemolizumab and placebo/nemolizumab groups). Study-JP02 patients received nemolizumab for 52 weeks. Both studies included an 8-week follow-up period.
RESULTS: Study-JP01 nemolizumab/nemolizumab and placebo/nemolizumab, and Study-JP02 nemolizumab groups comprised 143, 72 and 88 patients, respectively. In the nemolizumab/nemolizumab group, there were clinically meaningful improvements from the start of treatment to week 68 in the pruritus visual analogue scale (66% decrease) and Eczema Area and Severity Index (78% decrease). Quality of life (QoL) indicators improved after the first nemolizumab dose; improvements were maintained during the follow-up period. The long-term safety profile was consistent with previous studies, with no unexpected late-onset adverse events.
CONCLUSIONS: Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate-to-severe pruritus produced a continuous improvement in pruritus, signs of AD, and QoL for up to 68 weeks, with a favourable safety profile.
© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
E L Simpson, J-P Lacour, L Spelman, R Galimberti, L F Eichenfield, R Bissonnette, B A King, J P Thyssen, J I Silverberg, T Bieber, K Kabashima, Y Tsunemi, A Costanzo, E Guttman-Yassky, L A Beck, J M Janes, A M DeLozier, M Gamalo, D R Brinker, T Cardillo, F P Nunes, A S Paller, A Wollenberg, K Reich
Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials.
Br J Dermatol. 2020 Aug;183(2):242-255. doi: 10.1111/bjd.18898. Epub 2020 Mar 5.
Abstract/Text
BACKGROUND: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids.
OBJECTIVES: To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severe AD who had an inadequate response to topical therapies.
METHODS: In two independent, multicentre, double-blind, phase III monotherapy trials, BREEZE-AD1 and BREEZE-AD2, adults with moderate-to-severe AD were randomized 2 : 1 : 1 : 1 to once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks.
RESULTS: At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE-AD1 [N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%], and BREEZE-AD2 [N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%]. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg. Improvements in night-time awakenings, skin pain and quality-of-life measures were observed by week 1 for both 4 mg and 2 mg (P ≤ 0·05, all comparisons). The most common adverse events in patients treated with baricitinib were nasopharyngitis and headache. No cardiovascular events, venous thromboembolism, gastrointestinal perforation, significant haematological changes, or death were observed with any baricitinib dosage.
CONCLUSIONS: Baricitinib improved clinical signs and symptoms in patients with moderate-to-severe AD within 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development in AD, with no new safety concerns.
© 2020 British Association of Dermatologists.
E L Simpson, J-P Lacour, L Spelman, R Galimberti, L F Eichenfield, R Bissonnette, B A King, J P Thyssen, J I Silverberg, T Bieber, K Kabashima, Y Tsunemi, A Costanzo, E Guttman-Yassky, L A Beck, J M Janes, A M DeLozier, M Gamalo, D R Brinker, T Cardillo, F P Nunes, A S Paller, A Wollenberg, K Reich
Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials.
Br J Dermatol. 2020 Aug;183(2):242-255. doi: 10.1111/bjd.18898. Epub 2020 Mar 5.
Abstract/Text
BACKGROUND: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids.
OBJECTIVES: To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severe AD who had an inadequate response to topical therapies.
METHODS: In two independent, multicentre, double-blind, phase III monotherapy trials, BREEZE-AD1 and BREEZE-AD2, adults with moderate-to-severe AD were randomized 2 : 1 : 1 : 1 to once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks.
RESULTS: At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE-AD1 [N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%], and BREEZE-AD2 [N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%]. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg. Improvements in night-time awakenings, skin pain and quality-of-life measures were observed by week 1 for both 4 mg and 2 mg (P ≤ 0·05, all comparisons). The most common adverse events in patients treated with baricitinib were nasopharyngitis and headache. No cardiovascular events, venous thromboembolism, gastrointestinal perforation, significant haematological changes, or death were observed with any baricitinib dosage.
CONCLUSIONS: Baricitinib improved clinical signs and symptoms in patients with moderate-to-severe AD within 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development in AD, with no new safety concerns.
© 2020 British Association of Dermatologists.
Emma Guttman-Yassky, Henrique D Teixeira, Eric L Simpson, Kim A Papp, Aileen L Pangan, Andrew Blauvelt, Diamant Thaçi, Chia-Yu Chu, H Chih-Ho Hong, Norito Katoh, Amy S Paller, Brian Calimlim, Yihua Gu, Xiaofei Hu, Meng Liu, Yang Yang, John Liu, Allan R Tenorio, Alvina D Chu, Alan D Irvine
Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials.
Lancet. 2021 Jun 5;397(10290):2151-2168. doi: 10.1016/S0140-6736(21)00588-2. Epub 2021 May 21.
Abstract/Text
BACKGROUND: Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis.
METHODS: Measure Up 1 and Measure Up 2 were replicate multicentre, randomised, double-blind, placebo-controlled, phase 3 trials; Measure Up 1 was done at 151 clinical centres in 24 countries across Europe, North and South America, Oceania, and the Asia-Pacific region; and Measure Up 2 was done at 154 clinical centres in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region. Eligible patients were adolescents (aged 12-17 years) and adults (aged 18-75 years) with moderate-to-severe atopic dermatitis (≥10% of body surface area affected by atopic dermatitis, Eczema Area and Severity Index [EASI] score of ≥16, validated Investigator's Global Assessment for Atopic Dermatitis [vIGA-AD] score of ≥3, and Worst Pruritus Numerical Rating Scale score of ≥4). Patients were randomly assigned (1:1:1) using an interactive response technology system to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks, stratified by baseline disease severity, geographical region, and age. Coprimary endpoints were the proportion of patients who had achieved at least a 75% improvement in EASI score from baseline (EASI-75) and the proportion of patients who had achieved a vIGA-AD response (defined as a vIGA-AD score of 0 [clear] or 1 [almost clear] with ≥2 grades of reduction from baseline) at week 16. Efficacy was analysed in the intention-to-treat population and safety was analysed in all randomly assigned patients who received at least one dose of study drug. These trials are registered with ClinicalTrials.gov, NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2), and are both active but not recruiting.
FINDINGS: Between Aug 13, 2018, and Dec 23, 2019, 847 patients were randomly assigned to upadacitinib 15 mg (n=281), upadacitinib 30 mg (n=285), or placebo (n=281) in the Measure Up 1 study. Between July 27, 2018, and Jan 17, 2020, 836 patients were randomly assigned to upadacitinib 15 mg (n=276), upadacitinib 30 mg (n=282), or placebo (n=278) in the Measure Up 2 study. At week 16, the coprimary endpoints were met in both studies (all p<0·0001). The proportion of patients who had achieved EASI-75 at week 16 was significantly higher in the upadacitinib 15 mg (196 [70%] of 281 patients) and upadacitinib 30 mg (227 [80%] of 285 patients) groups than the placebo group (46 [16%] of 281 patients) in Measure Up 1 (adjusted difference in EASI-75 response rate vs placebo, 53·3% [95% CI 46·4-60·2] for the upadacitinib 15 mg group; 63·4% [57·1-69·8] for the upadacitinib 30 mg group) and Measure Up 2 (166 [60%] of 276 patients in the upadacitinib 15 mg group and 206 [73%] of 282 patients in the upadacitinib 30 mg group vs 37 [13%] of 278 patients in the placebo group; adjusted difference in EASI-75 response rate vs placebo, 46·9% [39·9-53·9] for the upadacitinib 15 mg group; 59·6% [53·1-66·2] for the upadacitinib 30 mg group). The proportion of patients who achieved a vIGA-AD response at week 16 was significantly higher in the upadacitinib 15 mg (135 [48%] patients) and upadacitinib 30 mg (177 [62%] patients) groups than the placebo group (24 [8%] patients) in Measure Up 1 (adjusted difference in vIGA-AD response rate vs placebo, 39·8% [33·2-46·4] for the upadacitinib 15 mg group; 53·6% [47·2-60·0] for the upadacitinib 30 mg group) and Measure Up 2 (107 [39%] patients in the upadacitinib 15 mg group and 147 [52%] patients in the upadacitinib 30 mg group vs 13 [5%] patients in the placebo group; adjusted difference in vIGA-AD response rate vs placebo, 34·0% [27·8-40·2] for the upadacitinib 15 mg group; 47·4% [41·0-53·7] for the upadacitinib 30 mg group). Both upadacitinib doses were well tolerated. The incidence of serious adverse events and adverse events leading to study drug discontinuation were similar among groups. The most frequently reported treatment-emergent adverse events were acne (19 [7%] of 281 patients in the upadacitinib 15 mg group, 49 [17%] of 285 patients in the upadacitinib 30 mg group, and six [2%] of 281 patients in the placebo group in Measure Up 1; 35 [13%] of 276 patients in the upadacitinib 15 mg group, 41 [15%] of 282 patients in the upadacitinib 30 mg group, and six [2%] of 278 patients in the placebo group in Measure Up 2), upper respiratory tract infection (25 [9%] patients, 38 [13%] patients, and 20 [7%] patients; 19 [7%] patients, 17 [16%] patients, and 12 [4%] patients), nasopharyngitis (22 [8%] patients, 33 [12%] patients, and 16 [6%] patients; 16 [6%] patients, 18 [6%] patients, and 13 [5%] patients), headache (14 [5%] patients, 19 [7%] patients, and 12 [4%] patients; 18 [7%] patients, 20 [7%] patients, and 11 [4%] patients), elevation in creatine phosphokinase levels (16 [6%] patients, 16 [6%] patients, and seven [3%] patients; nine [3%] patients, 12 [4%] patients, and five [2%] patients), and atopic dermatitis (nine [3%] patients, four [1%] patients, and 26 [9%] patients; eight [3%] patients, four [1%] patients, and 26 [9%] patients).
INTERPRETATION: Monotherapy with upadacitinib might be an effective treatment option and had a positive benefit-risk profile in adolescents and adults with moderate-to-severe atopic dermatitis.
FUNDING: AbbVie.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Lawrence F Eichenfield, Carsten Flohr, Robert Sidbury, Elaine Siegfried, Zsuzsanna Szalai, Ryszard Galus, Zhirong Yao, Hidetoshi Takahashi, Sébastien Barbarot, Claire Feeney, Fan Zhang, Marco DiBonaventura, Ricardo Rojo, Hernan Valdez, Gary Chan
Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial.
JAMA Dermatol. 2021 Oct 1;157(10):1165-1173. doi: 10.1001/jamadermatol.2021.2830.
Abstract/Text
IMPORTANCE: Dupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment with a favorable benefit-risk profile for adolescents with moderate-to-severe AD.
OBJECTIVE: To investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD.
DESIGN, SETTING, AND PARTICIPANTS: The phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion.
INTERVENTIONS: Patients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy.
MAIN OUTCOMES AND MEASURES: Coprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored.
RESULTS: This study included 285 adolescents with moderate-to-severe AD (145 boys [50.9%] and 140 girls [49.1%]), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P < .05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P < .05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P < .01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 [18.1%]) and 100 mg (7 [7.4%]). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs.
CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03796676.
J Schmitt, N Schmitt, M Meurer
Cyclosporin in the treatment of patients with atopic eczema - a systematic review and meta-analysis.
J Eur Acad Dermatol Venereol. 2007 May;21(5):606-19. doi: 10.1111/j.1468-3083.2006.02023.x.
Abstract/Text
OBJECTIVE: To systematically assess the effectiveness of systemic cyclosporin in patients with severe atopic eczema.
STUDY DESIGN: Systematic review and meta-analysis of controlled and uncontrolled trials. Electronic (MEDLINE, Cochrane databases) and hand search of published work. Independent standardized assessment of eligibility and data abstraction by two reviewers.
METHODS: For the qualitative review data on study design, study population, methodology, results, tolerability and methodological quality was independently extracted by two reviewers. Qualitatively homogeneous studies were pooled using a random-effects model. The mean relative change in objective disease severity was chosen as the main outcome measure for the quantitative analysis. Publication bias was explored by regressing treatment effect on sample size. Sensitivity analysis included meta-regression of study-specific covariates (inclusion of children, study type, concomitant topical therapy, study quality).
RESULTS: Fifteen studies including 602 patients met the eligibility criteria. In all studies analysed, cyclosporin consistently decreased the severity of atopic eczema. Twelve studies appeared homogeneous enough to be pooled. After 2 weeks of treatment we found a dose-related response with a pooled mean decrease in disease severity of 22% (95%-CI 8-36%) under low-dose cyclosporin ( 3 mg/kg) and 40% (95%-CI 29-51%) at dosages >or=4 mg/kg. After 6-8 weeks the relative effectiveness was 55% (95%-CI 48-62%).
CONCLUSIONS: Due to evidence of publication bias the quantitative results need to be interpreted with caution. Effectiveness of cyclosporin is similar in adults and children, but tolerability might be better in children. As data to adequately evaluate the long-term effectiveness and safety of cyclosporin in patients with atopic eczema are unavailable, long-term registries are encouraged.
J Schmitt, N Schmitt, M Meurer
Cyclosporin in the treatment of patients with atopic eczema - a systematic review and meta-analysis.
J Eur Acad Dermatol Venereol. 2007 May;21(5):606-19. doi: 10.1111/j.1468-3083.2006.02023.x.
Abstract/Text
OBJECTIVE: To systematically assess the effectiveness of systemic cyclosporin in patients with severe atopic eczema.
STUDY DESIGN: Systematic review and meta-analysis of controlled and uncontrolled trials. Electronic (MEDLINE, Cochrane databases) and hand search of published work. Independent standardized assessment of eligibility and data abstraction by two reviewers.
METHODS: For the qualitative review data on study design, study population, methodology, results, tolerability and methodological quality was independently extracted by two reviewers. Qualitatively homogeneous studies were pooled using a random-effects model. The mean relative change in objective disease severity was chosen as the main outcome measure for the quantitative analysis. Publication bias was explored by regressing treatment effect on sample size. Sensitivity analysis included meta-regression of study-specific covariates (inclusion of children, study type, concomitant topical therapy, study quality).
RESULTS: Fifteen studies including 602 patients met the eligibility criteria. In all studies analysed, cyclosporin consistently decreased the severity of atopic eczema. Twelve studies appeared homogeneous enough to be pooled. After 2 weeks of treatment we found a dose-related response with a pooled mean decrease in disease severity of 22% (95%-CI 8-36%) under low-dose cyclosporin ( 3 mg/kg) and 40% (95%-CI 29-51%) at dosages >or=4 mg/kg. After 6-8 weeks the relative effectiveness was 55% (95%-CI 48-62%).
CONCLUSIONS: Due to evidence of publication bias the quantitative results need to be interpreted with caution. Effectiveness of cyclosporin is similar in adults and children, but tolerability might be better in children. As data to adequately evaluate the long-term effectiveness and safety of cyclosporin in patients with atopic eczema are unavailable, long-term registries are encouraged.
ネオーラルによるアトピー性皮膚炎治療研究会. 成人の重症アトピー性皮膚炎患者を対象としたシクロスポリンMEPCとプラセボとの比較試験：多施設共同、ランダム化、二重盲検、並行群間比較試験. 臨皮 2009; 63: 73-82.
ネオーラルによるアトピー性皮膚炎治療研究会. 成人の重症アトピー性皮膚炎患者を対象としたシクロスポリンMEPCとプラセボとの比較試験：多施設共同、ランダム化、二重盲検、並行群間比較試験. 臨皮 2009; 63: 73-82.
Yoichi Chida, Andrew Steptoe, Noriaki Hirakawa, Nobuyuki Sudo, Chiharu Kubo
The effects of psychological intervention on atopic dermatitis. A systematic review and meta-analysis.
Int Arch Allergy Immunol. 2007;144(1):1-9. doi: 10.1159/000101940. Epub 2007 Apr 20.
Abstract/Text
BACKGROUND: Psychological interventions may be valuable in atopic dermatitis. We systematically reviewed and carried out a meta-analysis of randomized controlled trials of psychological interventions.
METHODS: Electronic searches and manual journal searches were carried out. Two coders independently coded study designs, participants, treatments and outcome characteristics of the studies meeting the selection criteria.
RESULTS: Eight journal articles published between 1986 and 2006 were included. Eight types of intervention were tested: aromatherapy, autogenic training, brief dynamic psychotherapy, cognitive-behavioral therapy, dermatological education and cognitive-behavioral therapy, habit reversal behavioral therapy, a stress management program, and structured educational programs. Effect sizes were computed as correlation coefficient (r), and random effects models were used in the analysis. For eczema severity, the average effect size for the 8 trials including 8 interventions was -0.367 [chi(2)(1) = 7.452, p = 0.006; 95% CI -0.579 to -0.108]. The average effect sizes on itching intensity (5 trials with 5 interventions) and scratching (5 trials with 4 interventions) were -0.805 [chi(2)(1) = 4.719, p = 0.030; 95% CI -0.971 to -0.108] and -0.620 [chi(2)(1) = 24.24, p < 0.0001; 95% CI -0.767 to -0.410], respectively.
CONCLUSIONS: Although the present meta-analysis revealed that psychological interventions had a significant ameliorating effect on eczema severity, itching intensity and scratching in atopic dermatitis patients, a definite conclusion about their effectiveness seems premature. Accordingly, future studies should involve more sophisticated methodologies, use established measures of outcome variables, adjust for possible confounders between the intervention and control groups, and provide sufficient data to calculate the effect sizes for future meta-analyses.
Yoichi Chida, Andrew Steptoe, Noriaki Hirakawa, Nobuyuki Sudo, Chiharu Kubo
The effects of psychological intervention on atopic dermatitis. A systematic review and meta-analysis.
Int Arch Allergy Immunol. 2007;144(1):1-9. doi: 10.1159/000101940. Epub 2007 Apr 20.
Abstract/Text
BACKGROUND: Psychological interventions may be valuable in atopic dermatitis. We systematically reviewed and carried out a meta-analysis of randomized controlled trials of psychological interventions.
METHODS: Electronic searches and manual journal searches were carried out. Two coders independently coded study designs, participants, treatments and outcome characteristics of the studies meeting the selection criteria.
RESULTS: Eight journal articles published between 1986 and 2006 were included. Eight types of intervention were tested: aromatherapy, autogenic training, brief dynamic psychotherapy, cognitive-behavioral therapy, dermatological education and cognitive-behavioral therapy, habit reversal behavioral therapy, a stress management program, and structured educational programs. Effect sizes were computed as correlation coefficient (r), and random effects models were used in the analysis. For eczema severity, the average effect size for the 8 trials including 8 interventions was -0.367 [chi(2)(1) = 7.452, p = 0.006; 95% CI -0.579 to -0.108]. The average effect sizes on itching intensity (5 trials with 5 interventions) and scratching (5 trials with 4 interventions) were -0.805 [chi(2)(1) = 4.719, p = 0.030; 95% CI -0.971 to -0.108] and -0.620 [chi(2)(1) = 24.24, p < 0.0001; 95% CI -0.767 to -0.410], respectively.
CONCLUSIONS: Although the present meta-analysis revealed that psychological interventions had a significant ameliorating effect on eczema severity, itching intensity and scratching in atopic dermatitis patients, a definite conclusion about their effectiveness seems premature. Accordingly, future studies should involve more sophisticated methodologies, use established measures of outcome variables, adjust for possible confounders between the intervention and control groups, and provide sufficient data to calculate the effect sizes for future meta-analyses.
N J Reynolds, V Franklin, J C Gray, B L Diffey, P M Farr
Narrow-band ultraviolet B and broad-band ultraviolet A phototherapy in adult atopic eczema: a randomised controlled trial.
Lancet. 2001 Jun 23;357(9273):2012-6. doi: 10.1016/S0140-6736(00)05114-X.
Abstract/Text
BACKGROUND: Narrow-band ultraviolet B (UVB) is an effective treatment for psoriasis, and open studies suggest that this phototherapy might improve atopic eczema. We did a randomised controlled trial to compare narrow-band UVB, UVA, and visible light phototherapy as second-line, adjunctive treatments in adult patients with moderate to severe atopic eczema.
METHODS: Phototherapy was administered twice a week for 12 weeks. 26 patients were randomly assigned narrow-band UVB, 24 were assigned UVA, and 23 visible fluorescent light. The primary endpoints were change in total disease activity (sum of scores at six body sites) and change in extent of disease after 24 treatments compared with baseline. Data were analysed by the method of summary measures.
FINDINGS: 13 patients withdrew or were excluded from analysis. Mean reductions in total disease activity over 24 treatments in patients who received narrow-band UVB and UVA, respectively, were 9.4 points (95% CI 3.6 to 15.2) and 4.4 points (-1.0 to 9.8) more than in patients who received visible light. Mean reductions in extent of disease after 24 treatments with narrow-band UVB and UVA were 6.7% (1.5 to 11.9) and -1.0% (-5.3 to 3.3) compared with visible light. A small proportion of patients developed erythema after phototherapy or had a flare in their eczema sufficient to withdraw from treatment.
INTERPRETATION: Narrow-band UVB is an effective adjunctive treatment for moderate to severe atopic eczema, and the treatment is well tolerated by most patients.
N J Reynolds, V Franklin, J C Gray, B L Diffey, P M Farr
Narrow-band ultraviolet B and broad-band ultraviolet A phototherapy in adult atopic eczema: a randomised controlled trial.
Lancet. 2001 Jun 23;357(9273):2012-6. doi: 10.1016/S0140-6736(00)05114-X.
Abstract/Text
BACKGROUND: Narrow-band ultraviolet B (UVB) is an effective treatment for psoriasis, and open studies suggest that this phototherapy might improve atopic eczema. We did a randomised controlled trial to compare narrow-band UVB, UVA, and visible light phototherapy as second-line, adjunctive treatments in adult patients with moderate to severe atopic eczema.
METHODS: Phototherapy was administered twice a week for 12 weeks. 26 patients were randomly assigned narrow-band UVB, 24 were assigned UVA, and 23 visible fluorescent light. The primary endpoints were change in total disease activity (sum of scores at six body sites) and change in extent of disease after 24 treatments compared with baseline. Data were analysed by the method of summary measures.
FINDINGS: 13 patients withdrew or were excluded from analysis. Mean reductions in total disease activity over 24 treatments in patients who received narrow-band UVB and UVA, respectively, were 9.4 points (95% CI 3.6 to 15.2) and 4.4 points (-1.0 to 9.8) more than in patients who received visible light. Mean reductions in extent of disease after 24 treatments with narrow-band UVB and UVA were 6.7% (1.5 to 11.9) and -1.0% (-5.3 to 3.3) compared with visible light. A small proportion of patients developed erythema after phototherapy or had a flare in their eczema sufficient to withdraw from treatment.
INTERPRETATION: Narrow-band UVB is an effective adjunctive treatment for moderate to severe atopic eczema, and the treatment is well tolerated by most patients.
I Man, I K Crombie, R S Dawe, S H Ibbotson, J Ferguson
The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up data.
Br J Dermatol. 2005 Apr;152(4):755-7. doi: 10.1111/j.1365-2133.2005.06537.x.
Abstract/Text
BACKGROUND: Limited information is available on the carcinogenic risk associated with narrowband TL-01 UVB phototherapy in humans.
OBJECTIVES: To determine the skin cancer incidence in a population treated with TL-01 phototherapy.
PATIENTS AND METHODS: All TL-01-treated patients were identified from the departmental computerized database. Patients with malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were identified by record linkage with the Scottish Cancer Registry. The incidence of each was compared with the normal Scottish population matched for age and sex.
RESULTS: Data were obtained from 1908 patients. The median follow-up duration was 4 years (range 0.04-13). The median cumulative number of TL-01 treatments and dose were 23 (1-199) and 13 337 (30-284 415) mJ cm(-2), respectively. No increased incidence of SCC or MM was observed. Ten patients developed BCC compared with an expected 4.7 in the Scottish population [standardized rate ratio 213 (95% confidence interval 102-391); P < 0.05].
CONCLUSIONS: A small but significant increase of BCC was detected in the TL-01 group. This could be explained by a number of factors, including ascertainment bias. To determine the true carcinogenic risk of TL-01 phototherapy, longer follow-up is essential.
I Man, I K Crombie, R S Dawe, S H Ibbotson, J Ferguson
The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up data.
Br J Dermatol. 2005 Apr;152(4):755-7. doi: 10.1111/j.1365-2133.2005.06537.x.
Abstract/Text
BACKGROUND: Limited information is available on the carcinogenic risk associated with narrowband TL-01 UVB phototherapy in humans.
OBJECTIVES: To determine the skin cancer incidence in a population treated with TL-01 phototherapy.
PATIENTS AND METHODS: All TL-01-treated patients were identified from the departmental computerized database. Patients with malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were identified by record linkage with the Scottish Cancer Registry. The incidence of each was compared with the normal Scottish population matched for age and sex.
RESULTS: Data were obtained from 1908 patients. The median follow-up duration was 4 years (range 0.04-13). The median cumulative number of TL-01 treatments and dose were 23 (1-199) and 13 337 (30-284 415) mJ cm(-2), respectively. No increased incidence of SCC or MM was observed. Ten patients developed BCC compared with an expected 4.7 in the Scottish population [standardized rate ratio 213 (95% confidence interval 102-391); P < 0.05].
CONCLUSIONS: A small but significant increase of BCC was detected in the TL-01 group. This could be explained by a number of factors, including ascertainment bias. To determine the true carcinogenic risk of TL-01 phototherapy, longer follow-up is essential.
