Cunliffe WJ, Poncet M, Loesche C, Verschoore M.
A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials.
Br J Dermatol. 1998 Oct;139 Suppl 52:48-56. doi: 10.1046/j.1365-2133.1998.1390s2048.x.
Abstract/Text
The purpose of this meta-analysis was to determine if adapalene 0.1% gel (Differin) provided superior efficacy and better tolerability than tretinoin 0.025% gel in the treatment of acne vulgaris. All comparative studies, both published and unpublished, from the United States and Europe, that fulfilled rigorous protocol criteria (multicentre, randomized, investigator-blind) were used. Five comparative studies met these criteria. In total, the meta-analysis evaluated 900 patients (450 treated with adapalene 0.1% gel, 450 treated with tretinoin 0.025% gel) with mild-to-moderate acne from the combined clinical trials. To avoid study bias, the meta-analysis used an intention-to-treat analysis. Statistical methodology for the meta-analysis included analysis of covariance, analysis of variance and Cochran-Mantel-Haenszel test. All statistical tests were two-sided, with the 0.05 probability level used to establish statistical significance, and 95% confidence intervals used to assess equivalence. Adapalene demonstrated equivalent efficacy to tretinoin in terms of reducing total lesion count. Adapalene demonstrated more rapid efficacy, as evidenced by a significant difference in the reduction of inflammatory and total lesions at week 1. Adapalene also demonstrated considerably greater local tolerability at all evaluation periods. The findings from this meta-analysis suggest that adapalene 0.1% gel constitutes a pharmacologic advance over such classic retinoids as tretinoin for the treatment of acne vulgaris.
Kawashima M, Harada S, Loesche C, Miyachi Y.
Adapalene gel 0.1% is effective and safe for Japanese patients with acne vulgaris: a randomized, multicenter, investigator-blinded, controlled study.
J Dermatol Sci. 2008 Mar;49(3):241-8. doi: 10.1016/j.jdermsci.2007.09.012. Epub 2007 Dec 11.
Abstract/Text
BACKGROUND: Topical retinoids, such as adapalene, are an integral part of acne therapy in most regions and are considered appropriate first-line therapy by international guidelines for all cases of acne with the exception of the most severe. However, there are currently no topical retinoids available for the treatment of acne vulgaris in Japan.
OBJECTIVE: To confirm efficacy and safety of adapalene gel 0.1% versus the corresponding gel vehicle in the treatment of Japanese patients with acne vulgaris for up to 12 weeks.
METHODS: A total of 200 patients were randomized to receive adapalene gel 0.1%, or vehicle once-daily for 12 weeks. Percent reduction in lesion counts (total, inflammatory, and non-inflammatory) and subject satisfaction were evaluated. Safety was monitored through adverse events and laboratory tests.
RESULTS: Adapalene gel 0.1% produced significantly better reductions in total (P<0.0001), inflammatory (P=0.0010), and non-inflammatory lesions (P<0.0001) at endpoint (week 12, last observation carried forward) than gel vehicle, with a higher overall subject satisfaction. The primary efficacy variable, the median percent reduction of total lesion counts at endpoint, was significantly greater with adapalene gel 0.1% (63.2%) compared to that with the vehicle (36.9%) in the ITT population (P<0.0001). Significantly greater results were observed as early as week 1. Adapalene was well tolerated, with adverse events that were mostly mild-to-moderate and transient in nature.
CONCLUSIONS: Adapalene gel 0.1% was effective in the treatment of acne vulgaris in Japanese patients. Adapalene was safe and well tolerated, consistent with the good tolerability profile demonstrated in other patient populations.
Wolf JE Jr, Kaplan D, Kraus SJ, Loven KH, Rist T, Swinyer LJ, Baker MD, Liu YS, Czernielewski J.
Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study.
J Am Acad Dermatol. 2003 Sep;49(3 Suppl):S211-7. doi: 10.1067/s0190-9622(03)01152-6.
Abstract/Text
This multicenter, randomized, investigator-blinded study investigated the efficacy and tolerability of adapalene gel 0.1% plus clindamycin phosphate lotion 1%, compared with clindamycin plus vehicle for the treatment of mild to moderate acne vulgaris. A total of 249 patients applied clindamycin lotion twice daily and adapalene (125 patients) or vehicle gel (124 patients) once daily for 12 weeks. A significantly greater reduction of total (P <.001), inflammatory (P =.004) and noninflammatory lesions (P <.001) was seen in the clindamycin plus adapalene group than in the clindamycin plus vehicle group. These significant treatment effects were observed as early as week 4 for both noninflammatory and total lesion counts. Both treatment regimens were well tolerated. Although the worst scores for scaling (P <.05), dryness (P <.01), and stinging/burning (P <.05) were higher in the clindamycin plus adapalene group than in the clindamycin plus vehicle group in patients with moderate or severe irritation; in most cases these symptoms were of mild intensity.
Seidler EM, Kimball AB.
Meta-analysis comparing efficacy of benzoyl peroxide, clindamycin, benzoyl peroxide with salicylic acid, and combination benzoyl peroxide/clindamycin in acne.
J Am Acad Dermatol. 2010 Jul;63(1):52-62. doi: 10.1016/j.jaad.2009.07.052. Epub 2010 May 21.
Abstract/Text
BACKGROUND: Comparative efficacy of the multiple treatments containing benzoyl peroxide (BPO) and clindamycin (CL) is not established.
OBJECTIVE: We compared the efficacy of topical 5% BPO, 1% to 1.2% CL, 5% BPO with salicylic acid (SA) preparation, and combination BPO/CL in acne lesion reduction.
METHODS: A meta-analysis was conducted using the Cochrane collaboration guidelines in accordance with the PRISMA statement.
RESULTS: A total of 23 studies including 7309 patients were used in the meta-analysis. At 2 to 4 weeks, 5% BPO + SA had statistically greater percent lesion reductions over other groups (weighted mean inflammatory lesion reduction: BPO = 33.4%, CL = 21.5%, BPO + SA = 55.2%, BPO/CL = 40.7%, placebo = 7.3%; weighted mean noninflammatory lesion reduction: BPO = 19.1%, CL = 10.0%, BPO + SA = 42.7%, BPO/CL = 26.2%, placebo = 6.7%). At 10- to 12-week end points, 5% BPO + SA and BPO/CL were similar, with overlapping confidence intervals (weighted mean inflammatory lesion reduction: BPO = 43.7%, CL = 45.9%, BPO + SA = 51.8%, BPO/CL = 55.6%, placebo = 26.8%; weighted mean noninflammatory lesion reduction: BPO = 30.9%, CL = 32.6%, BPO + SA = 47.8%, BPO/CL = 40.3%, placebo = 17.0%).
LIMITATIONS: Trial heterogeneity, publication bias, and deficits in the reporting of individual primary studies may affect results.
CONCLUSION: At early time points, 5% BPO + SA had the best profile. BPO/CL was only incrementally better than BPO alone but was superior to CL alone. At later time points, 5% BPO + SA was similar to BPO/CL.
Copyright (c) 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Thiboutot DM, Shalita AR, Yamauchi PS, Dawson C, Arsonnaud S, Kang S; Differin Study Group.
Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator-blind, randomized, controlled study.
Skinmed. 2005 May-Jun;4(3):138-46. doi: 10.1111/j.1540-9740.2005.04279.x.
Abstract/Text
BACKGROUND: Combination therapy with a topical retinoid and an antibiotic is recognized as a rational and effective approach for the treatment of acne vulgaris. Adapalene, a naphthoic acid derivative with anti-inflammatory and receptor-selective retinoid properties, is safe and well tolerated. While the combination of adapalene with oral or topical antibiotics has been shown to deliver a superior and faster response than an antibiotic alone, the clinical benefits of a combination of adapalene and doxycycline, the most frequently prescribed oral antibiotic for acne in the United States, have yet to be evaluated.
OBJECTIVE AND METHODS: In a 12-week study, the efficacy and safety of the combination of adapalene gel 0.1% with doxycycline was compared with doxycycline alone for the treatment of severe acne. Subjects were randomized to receive doxycycline once daily in the morning and either adapalene or vehicle once daily in the evening.
RESULTS: At Week 12, the combination adapalene-doxycycline was significantly superior to doxycycline alone for change from baseline in total (p<0.001), inflammatory (p=0.02), and noninflammatory (p<0.001) lesions. Significant differences in total lesions were observed as early as Week 4 (p=0.04). Both treatments were well tolerated, and no serious adverse events were reported.
CONCLUSIONS: The study demonstrates that the combination of adapalene and an oral antibiotic provides a superior and faster benefit than antibiotic therapy alone and should be considered at the initiation of treatment.
Cunliffe WJ, Meynadier J, Alirezai M, George SA, Coutts I, Roseeuw DI, Hachem JP, Briantais P, Sidou F, Soto P.
Is combined oral and topical therapy better than oral therapy alone in patients with moderate to moderately severe acne vulgaris? A comparison of the efficacy and safety of lymecycline plus adapalene gel 0.1%, versus lymecycline plus gel vehicle.
J Am Acad Dermatol. 2003 Sep;49(3 Suppl):S218-26. doi: 10.1067/s0190-9622(03)01153-8.
Abstract/Text
This multicenter, randomized, investigator-blinded study compared the efficacy and tolerability of a combination of lymecycline 300 mg/day orally and adapalene topical gel 0.1% (n = 118) to lymecycline 300 mg/day orally plus vehicle gel (n = 124) in patients with moderate to moderately severe acne vulgaris with both inflammatory and noninflammatory lesions. The primary efficacy end point, total lesion count at end point (last observation carried forward), showed a statistically significant difference in favor of the lymecycline plus adapalene group (P =.0011). The mean decrease in total, inflammatory and noninflammatory lesion counts was significantly greater at end point in the lymecycline plus adapalene group than in the lymecycline plus vehicle group (P <.01). In addition, a significant difference for inflammatory and total acne lesions was seen sooner in the adapalene plus lymecycline group. In total, 75.5% of patients in the lymecycline plus adapalene group were markedly improved, almost clear or clear of their lesions at week 12, compared with 51.8% of those in the lymecycline plus vehicle group (P <.001). Local cutaneous tolerance was generally good in both groups, although more patients receiving the lymecycline plus adapalene combination experienced cutaneous reactions than those receiving lymecycline plus vehicle. There are relatively few studies comparing the efficacy of combined oral and topical therapy with either individual therapy alone. This study clearly demonstrates that lymecycline plus adapalene combination treatment resulted in a significantly greater mean decrease in the number of inflammatory, noninflammatory and total lesions than lymecycline plus vehicle and was well tolerated.
Kuhlman DS, Callen JP.
A comparison of clindamycin phosphate 1 percent topical lotion and placebo in the treatment of acne vulgaris.
Cutis. 1986 Sep;38(3):203-6.
Abstract/Text
The efficacy and skin tolerance of 1 percent clindamycin phosphate lotion were compared with those of the placebo for the lotion in a randomized, double-blind, 12-week study in forty-six patients with moderate to severe acne vulgaris. Patients using the 1 percent clindamycin lotion experienced reductions in numbers of pustules, papules, open comedones, and nodulocystic lesions. Papule counts were also reduced in placebo-treated patients. The group using clindamycin lotion had significantly greater reductions in pustule counts at week 12 and papule counts at week 3 than the placebo-treated group. Nearly 90 percent of the evaluable patients at week 12 experienced improvement or marked improvement in their acne according to the physician's evaluation, regardless of treatment group. Both regimens were well tolerated. Although diarrhea was reported by eight patients (three taking clindamycin, five receiving placebo), no patients discontinued the protocol because of diarrhea. This study demonstrated the efficacy of 1 percent clindamycin topical lotion in the treatment of moderate to severe acne vulgaris.
Alirezaï M, Gerlach B, Horvath A, Forsea D, Briantais P, Guyomar M.
Results of a randomised, multicentre study comparing a new water-based gel of clindamycin 1% versus clindamycin 1% topical solution in the treatment of acne vulgaris.
Eur J Dermatol. 2005 Jul-Aug;15(4):274-8.
Abstract/Text
Several topical formulations of clindamycin phosphate are currently marketed for the treatment of acne vulgaris. This 12 week, multi-centre, investigator-blind, randomised, active and placebo-controlled, parallel group study assessed the clinical efficacy and safety of clindamycin 1% gel once-a-day vs clindamycin 1% solution twice-a-day, and to demonstrate its superiority vs its vehicle alone. A total of 592 subjects were included. After 12 weeks, a 65% reduction in inflammatory lesion count was observed with both active treatments. The gel was superior to its vehicle for total and inflammatory lesion reduction, Global Assessment of Improvement, and Global Severity Grade at final visit (all p < 0.01). No difference was found between the 2 active treatments for any of the evaluated criteria. Local tolerance in each active treatment group was slightly better with clindamycin gel (1.9% of subjects) relative to 3.1% in the topical solution group. In conclusion, the new water-based gel once-a-day formulation of clindamycin 1% is an effective, safe, and convenient alternative to the twice-a-day topical solution formulation in the treatment of acne vulgaris.
Shalita AR, Myers JA, Krochmal L, Yaroshinsky A; Clindamycin Foam Study Group.
The safety and efficacy of clindamycin phosphate foam 1% versus clindamycin phosphate topical gel 1% for the treatment of acne vulgaris.
J Drugs Dermatol. 2005 Jan-Feb;4(1):48-56.
Abstract/Text
Clindamycin phosphate is the most widely used topical antibacterial agent for acne treatment. Treatment of patients with mild to moderate acne vulgaris with a new foam formulation (clindamycin foam, CF) for 12 weeks was at least as effective as clindamycin gel (CG) based on the Investigator's Static Global Assessment (ISGA) score. CF was superior to CG based on the reduction from baseline in total (P = .0014), inflammatory (P = .0478), and noninflammatory (P = .0037) acne lesion counts. Additionally, CF achieved efficacy that was superior to that of vehicle foam based on ISGA score (P = .0025) and all 3 lesion counts (all P < .05). Adverse experiences in the active treatment groups were mild or moderate and transient in nature. Thus the foam formulation of clindamycin is a safe and effective acne treatment; the unique foam delivery vehicle may offer cosmetic benefits to the patient and thus increase compliance.
Plewig G, Holland KT, Nenoff P.
Clinical and bacteriological evaluation of nadifloxacin 1% cream in patients with acne vulgaris: a double-blind, phase III comparison study versus erythromycin 2% cream.
Eur J Dermatol. 2006 Jan-Feb;16(1):48-55.
Abstract/Text
The aim of this double-blind, multinational, phase III study was to investigate the clinical and bacteriological efficacy of nadifloxacin 1% cream compared with erythromycin 2% cream in 474 European patients with predominantly inflamed slight-to-moderate acne vulgaris. During 12 weeks of treatment both nadifloxacin and erythromycin caused significant reduction in the number of inflamed papulo-pustular lesions (66.7% and 64.7%, respectively) and open and closed comedones. The microbiological evaluation showed a significant reduction of coagulase negative staphylococci (CNS) only in the nadifloxacin group, while Propionibacterium acnes was significantly reduced by both formulations. A significantly higher resistance and the extent of resistant of P. acnes and CNS against erythromycin compared to nadifloxacin were also evidenced. All adverse events reported were minor in both groups. This pivotal erythromycin-controlled study has demonstrated that nadifloxacin 1% cream was as efficacious and safe as erythromycin 2% and extremely low numbers of nadifloxacin-resistant microorganisms were detected in the treatment period.
Jung JY, Kwon HH, Yeom KB, Yoon MY, Suh DH.
Clinical and histological evaluation of 1% nadifloxacin cream in the treatment of acne vulgaris in Korean patients.
Int J Dermatol. 2011 Mar;50(3):350-7. doi: 10.1111/j.1365-4632.2010.04701.x.
Abstract/Text
OBJECTIVES: Nadifloxacin is a fluoroquinolone with broad-spectrum antibacterial activity. Although it is used as an acne treatment in some European countries, it has not been used to treat Korean acne patients. We aimed to evaluate the clinical efficacy and safety of 1% nadifloxacin cream and the histological changes it incurs when used to treat mild to moderate facial acne in Korean patients.
METHODS: An eight-week, randomized, prospective, split-face, double-blind, vehicle-controlled trial was performed. All participants were treated with 1% nadifloxacin cream on one-half of the face and vehicle cream on the other, twice per day for eight weeks.
RESULTS: At final visits, inflammatory acne lesions were reduced by 70% on nadifloxacin-treated skin and increased by 13.5% on vehicle-treated skin; non-inflammatory acne lesions showed reductions of 48.1 and 10.1%, respectively. A significant difference was observed between the two treatments at four weeks. Histopathological examinations of the acne lesions showed decreased inflammation and interleukin-8 expression but no change in transforming growth factor-β expression in nadifloxacin-treated skin compared with vehicle-treated skin after eight weeks of treatment.
CONCLUSIONS: Nadifloxacin 1% cream is an effective, safe, and well-tolerated topical treatment for Korean patients with mild to moderate acne vulgaris. Histopathological changes after nadifloxacin treatment were well correlated with clinical outcomes. Therefore, nadifloxacin can be used as an effective and safe treatment option in the management of mild to moderate acne in Asian subjects.
© 2011 The International Society of Dermatology.
Garner SE, Eady EA, Popescu C, Newton J, Li WA.
Minocycline for acne vulgaris: efficacy and safety.
Cochrane Database Syst Rev. 2003;(1):CD002086. doi: 10.1002/14651858.CD002086.
Abstract/Text
BACKGROUND: Minocycline is a tetracycline antibiotic that is commonly used in the treatment of moderate to severe acne vulgaris. Although it is more convenient for patients to take than first-generation tetracyclines, as it only needs to be taken once or twice a day and can be taken with food, it is more expensive. Concerns have also been expressed over its safety following the deaths of two patients taking the drug. There is a lack of consensus among dermatologists over the relative risks and benefits of minocycline. As most acne prescribing is undertaken by general practitioners, it is important that guidelines issued to them are based on the best available evidence rather than personal judgements.
OBJECTIVES: To collate and evaluate the evidence on the clinical efficacy of minocycline in the treatment of inflammatory acne vulgaris. Specific objectives were to compare the efficacy of minocycline with other drug treatments for acne and to collate information on the incidence of adverse drug reactions.
SEARCH STRATEGY: Randomised controlled trials (RCTs) of minocycline for acne vulgaris were identified by searching the following electronic databases; MEDLINE, EMBASE, Biosis, Biological Abstracts, International Pharmaceutical Abstracts, Cochrane Skin Group's Trial Register, Theses Online, BIDS ISI Science Citation Index, National Research Register, Current Controlled Trials and Bids Index to Scientific and Technical Proceedings. Other strategies used were scanning the references of articles retrieved, hand-searching of major dermatology journals and personal communication with trialists and drug companies.
SELECTION CRITERIA: To be eligible for the review, studies had to be RCTs comparing the efficacy of minocycline at any dose to active or placebo control, in subjects with inflammatory acne vulgaris. Diagnoses of papulo-pustular, polymorphic and nodular acne were also accepted. Trials were not excluded on the basis of language.
DATA COLLECTION AND ANALYSIS: 27 randomised controlled trials met the inclusion criteria and were included in this review. The comparators used were placebo (2 studies), oxytetracycline (1), tetracycline (6), doxycycline (7), lymecycline (2), topical clindamycin (3), topical erythromycin/zinc (1), cyproterone acetate/ ethinyloestradiol (1), oral isotretinoin (2), topical fusidic acid (1) and there was one dose response study. Two studies are ongoing and it remains to be clarified whether one further study is a RCT. Major outcome measures used in the trials included lesion counts, acne grades/severity scores, doctors' and patients' global assessments, adverse drug reactions and drop out rates. The quality of each study was assessed independently by two assessors and an effect size calculated where possible. An additional three RCTs and three safety studies were identified by searches conducted in November 2002; these will be reviewed for a major update in early 2003 when it is anticipated that the results of the two ongoing studies will be available.
MAIN RESULTS: The trials were generally small and of poor quality and in many cases the published reports were inadequate for our purpose. Pooling of the studies was not attempted due to the lack of common outcome measures and endpoints and the unavailability of some primary data. Although minocycline was shown to be an effective treatment for acne vulgaris, in only two studies was it found to be superior to other tetracyclines. Both of these were conducted under open conditions and had serious methodological problems. A third study showed it to be more effective than 2% fusidic acid, applied topically, against inflammatory lesions in mild to moderate acne. Differences in the way adverse drug reactions were identified could have accounted for the wide variation between studies in numbers of events reported. This meant that no overall evaluation could be made of incidence rates of adverse events associated with minocycline therapy. No RCT evidence was found to support the benefits of minocycline in acne resistant to other therapies and the dose response has only been evaluated up to eight weeks of therapy.
REVIEWER'S CONCLUSIONS: Minocycline is likely to be an effective treatment for moderate acne vulgaris, but this review found no reliable RCT evidence to justify its continued use first-line, especially given the price differential and the concerns that still remain about its safety. Its efficacy relative to other acne therapies could not be reliably determined due to the poor methodological quality of the trials and lack of consistent choice of outcome measures. Similarly the relative risk of adverse drug reactions could not be ascertained reliably and no recommendations can be made concerning the appropriate dose that should be used. It is hoped that this review will highlight the inadequacy of acne trials in general and encourage improvements in methodological quality and standards of reporting.
Arowojolu AO, Gallo MF, Lopez LM, Grimes DA, Garner SE.
Combined oral contraceptive pills for treatment of acne.
Cochrane Database Syst Rev. 2009 Jul 8;(3):CD004425. doi: 10.1002/14651858.CD004425.pub4. Epub 2009 Jul 8.
Abstract/Text
BACKGROUND: Acne is a common skin disorder among women. Although no uniform approach to the management of acne exists, combination oral contraceptives (COCs), which contain an estrogen and a progestin, often are prescribed for women.
OBJECTIVES: To determine the effectiveness of combined oral contraceptives (COCs) for the treatment of facial acne compared to placebo or other active therapies.
SEARCH STRATEGY: We searched for randomized controlled trials of COCs and acne in the computerized databases of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, and LILACS. We also searched for clinical trials in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). We wrote to authors of identified trials to seek any unpublished or published trials that we might have missed.
SELECTION CRITERIA: All randomized controlled trials reported in any language that compared the effectiveness of a COC containing an estrogen and a progestin to placebo or another active therapy for acne in women were eligible.
DATA COLLECTION AND ANALYSIS: We extracted data on total and specific (i.e., open or closed comedones, papules, pustules and nodules) facial lesion counts; acne severity grades; global assessments by the clinician or the participant and discontinuation due to adverse events. Data were entered and analyzed in RevMan.
MAIN RESULTS: The search yielded 25 trials: 7 placebo-controlled trials made 4 different comparisons, 17 trials made 13 comparisons between 2 different COC regimens, and 1 additional trial compared a COC to an antibiotic. COCs reduced acne lesion counts, severity grades and self-assessed acne compared to placebo. Differences in the comparative effectiveness of COCs containing varying progestin types and dosages, though, were less clear. COCs that contained chlormadinone acetate or cyproterone acetate improved acne better than levonorgestrel, although this apparent advantage was based on limited data. A COC with cyproterone acetate might result in better acne outcomes than one with desogestrel; however, the three studies comparing these COCs produced conflicting results. Likewise, levonorgestrel showed a slight improvement over desogestrel in acne outcomes in one trial, but a second trial found the COC groups were similar.
AUTHORS' CONCLUSIONS: The four COCs evaluated in placebo-controlled trials are effective in reducing inflammatory and non-inflammatory facial acne lesions. Few important differences were found between COC types in their effectiveness for treating acne. How COCs compare to alternative acne treatments is unknown since limited data were available regarding this question.
Magin P, Pond D, Smith W, Watson A.
A systematic review of the evidence for 'myths and misconceptions' in acne management: diet, face-washing and sunlight.
Fam Pract. 2005 Feb;22(1):62-70. doi: 10.1093/fampra/cmh715. Epub 2005 Jan 11.
Abstract/Text
BACKGROUND: Lay perceptions that diet, hygiene and sunlight exposure are strongly associated with acne causation and exacerbation are common but at variance with the consensus of current dermatological opinion.
OBJECTIVES: The objective of this study was to carry out a review of the literature to assess the evidence for diet, face-washing and sunlight exposure in acne management.
METHODS: Original studies were identified by searches of the Medline, EMBASE, AMED (Allied and Complementary Medicine), CINAHL, Cochrane, and DARE databases. Methodological information was extracted from identified articles but, given the paucity of high quality studies found, no studies were excluded from the review on methodological grounds.
RESULTS: Given the prevalence of lay perceptions, and the confidence of dermatological opinion in rebutting these perceptions as myths and misconceptions, surprisingly little evidence exists for the efficacy or lack of efficacy of dietary factors, face-washing and sunlight exposure in the management of acne. Much of the available evidence has methodological limitations.
CONCLUSIONS: Based on the present state of evidence, clinicians cannot be didactic in their recommendations regarding diet, hygiene and face-washing, and sunlight to patients with acne. Advice should be individualized, and both clinician and patient cognizant of its limitations.
Lookingbill DP, Chalker DK, Lindholm JS, Katz HI, Kempers SE, Huerter CJ, Swinehart JM, Schelling DJ, Klauda HC.
Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: combined results of two double-blind investigations.
J Am Acad Dermatol. 1997 Oct;37(4):590-5. doi: 10.1016/s0190-9622(97)70177-4.
Abstract/Text
BACKGROUND: It has previously been shown that a combination of erythromycin and benzoyl peroxide is superior to either ingredient when used alone in the treatment of acne. A clindamycin/benzoyl peroxide combination gel might have an advantage over erythromycin/benzoyl peroxide gel because the former does not require refrigeration after it is dispensed.
OBJECTIVE: Our purpose was to determine the efficacy and safety of a combination clindamycin/benzoyl peroxide gel when compared with benzoyl peroxide, clindamycin, or vehicle gels.
METHODS: In two double-blind, randomized, parallel, vehicle-controlled trials, patients were treated for 11 weeks with once-nightly application of one of the above preparations. Evaluations were performed at 2, 5, 8, and 11 weeks and included lesion counts and assessment of global responses and irritant effects.
RESULTS: A total of 334 patients completed the study. All three active preparations were significantly superior to the vehicle in global improvement and in reducing inflammatory lesions and noninflammatory lesions. The combination gel was significantly superior to the two individual agents in global improvement and reduction of inflammatory lesions and also to the clindamycin gel in reducing noninflammatory lesions. There was no significant difference in tolerance to the active gels versus the vehicle gel.
CONCLUSION: In the treatment of acne, topical clindamycin/benzoyl peroxide combination gel is well tolerated and superior to either individual ingredient.
日本皮膚科学会：尋常性痤瘡・酒皶治療ガイドライン2023．日皮会誌：2023;133（3）:407-450. Available from: https://www.dermatol.or.jp/uploads/uploads/files/guideline/zasou2023.pdf
Gollnick HP, Draelos Z, Glenn MJ, Rosoph LA, Kaszuba A, Cornelison R, Gore B, Liu Y, Graeber M; Adapalene-BPO Study Group.
Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients.
Br J Dermatol. 2009 Nov;161(5):1180-9. doi: 10.1111/j.1365-2133.2009.09209.x. Epub 2009 May 21.
Abstract/Text
BACKGROUND: Combination therapy utilizing agents with complementary mechanisms of action is recommended by acne guidelines to help simultaneously target multiple pathogenic factors. A unique, topical, fixed-dose combination gel with adapalene 0.1% and benzoyl peroxide (BPO) 2.5% has recently been developed for the once-daily treatment of acne.
OBJECTIVES: To evaluate the efficacy and safety of adapalene 0.1%-BPO 2.5% fixed-dose combination gel (adapalene-BPO) relative to adapalene 0.1% monotherapy (adapalene), BPO 2.5% monotherapy (BPO), and the gel vehicle (vehicle) in a large population for the treatment of acne vulgaris.
METHODS: In total, 1670 subjects were randomized in a double-blind controlled trial to receive adapalene-BPO, adapalene, BPO or vehicle for 12 weeks (1 : 1 : 1 : 1 randomization). Evaluations included success rate (subjects 'clear' or 'almost clear'), percentage change in lesion count from baseline, cutaneous tolerability and adverse events.
RESULTS: Adapalene-BPO was significantly more effective than corresponding monotherapies, with significant differences in percentage lesion count change observed as early as 1 week. Cutaneous tolerability profile was similar to adapalene. Adverse events were more frequent with the combination therapy (mainly due to an increase in mild-to-moderate dry skin), occurred early in the study, and were transient.
CONCLUSIONS: Adapalene-BPO provides significantly greater and synergistic efficacy and a faster onset of action with an acceptable safety profile in the treatment of acne vulgaris when compared with the corresponding vehicle and the adapalene and BPO monotherapies.
Thiboutot DM, Weiss J, Bucko A, Eichenfield L, Jones T, Clark S, Liu Y, Graeber M, Kang S; Adapalene-BPO Study Group.
Adapalene-benzoyl peroxide, a fixed-dose combination for the treatment of acne vulgaris: results of a multicenter, randomized double-blind, controlled study.
J Am Acad Dermatol. 2007 Nov;57(5):791-9. doi: 10.1016/j.jaad.2007.06.006. Epub 2007 Jul 26.
Abstract/Text
BACKGROUND: A fixed-dose combination gel with adapalene 0.1% and benzoyl peroxide (BPO) 2.5% has been developed for the once-daily treatment of acne.
OBJECTIVE: To evaluate the efficacy and safety of adapalene 0.1% -BPO 2.5% fixed combination gel (adapalene-BPO) for the treatment of acne.
METHODS: A total of 517 subjects were randomized in a double-blind controlled trial to receive either adapalene-BPO, adapalene, BPO, or vehicle for 12 weeks (2:2:2:1 randomization). Evaluation included success rate (subjects "clear" or "almost clear"), lesion count, cutaneous tolerability, and adverse events.
RESULTS: The fixed-dose combination gel of adapalene and BPO was significantly more effective than corresponding monotherapies, with significant differences in total lesion counts observed as early as 1 week. Adverse event frequency and cutaneous tolerability profile for adapalene-BPO were similar to adapalene monotherapy.
LIMITATIONS: These data were generated in a controlled trial. Results obtained in clinical practice could differ.
CONCLUSIONS: The fixed-dose combination of adapalene and BPO provides significantly greater efficacy for the treatment of acne vulgaris as early as week 1 relative to monotherapies, with a comparable safety profile to adapalene.
宮地良樹，Mizzi F，三田哲也，白立岩，生駒晃彦：日本人尋常性痤瘡患者を対象としたアダパレン0.1%/過酸化ベンゾイル2.5%配合ゲルの多施設共同，無作為化，二重盲検，実薬対照，平行群間比較，第III相臨床試験，皮膚の科学，2016；15：278―293．.
Dréno B, Kaufmann R, Talarico S, Torres Lozada V, Rodríguez-Castellanos MA, Gómez-Flores M, De Maubeuge J, Berg M, Foley P, Sysa-Jedrzejowska A, Kerrouche N, Paliargues F, Bettoli V.
Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study.
Br J Dermatol. 2011 Aug;165(2):383-90. doi: 10.1111/j.1365-2133.2011.10374.x. Epub 2011 Jul 6.
Abstract/Text
BACKGROUND: Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first-line option in the treatment of moderate to severe acne vulgaris.
OBJECTIVES: To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%-BPO 2·5% (A/BPO) fixed-dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris.
METHODS: A total of 378 subjects were randomized in a double-blind, controlled trial to receive once-daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects 'clear' or 'almost clear'), skin tolerability, adverse events and patients' satisfaction.
RESULTS: The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (-74·1%) than in the lymecycline with vehicle group (-56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P < 0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were 'very satisfied' was significantly greater (P = 0·031).
CONCLUSION: These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris.
© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.
Gold LS, Cruz A, Eichenfield L, Tan J, Jorizzo J, Kerrouche N, Dhuin JC.
Effective and safe combination therapy for severe acne vulgaris: a randomized, vehicle-controlled, double-blind study of adapalene 0.1%-benzoyl peroxide 2.5% fixed-dose combination gel with doxycycline hyclate 100 mg.
Cutis. 2010 Feb;85(2):94-104.
Abstract/Text
There is a paucity of treatment options for severe acne vulgaris aside from oral isotretinoin. This randomized, vehicle-controlled, multicenter, double-blind study evaluated the efficacy and safety of combination therapy using adapalene 0.1%-benzoyl peroxide 2.5% (A/BPO) fixed-dose combination gel with doxycycline hyclate 100 mg in the treatment of severe acne vulgaris. A total of 459 participants were randomized in a 1:1 ratio to receive oral doxycycline hyclate 100 mg once daily and either A/BPO or vehicle once daily for 12 weeks. Efficacy in the A/BPO with doxycycline group was demonstrated as early as week 2 compared with the vehicle arm for total, inflammatory, and noninflammatory lesions (all P < .005). At week 12, this combination was superior to vehicle with doxycycline in reducing total, inflammatory, and noninflammatory lesion counts (an added incremental benefit of 23%, 24%, and 21%, respectively), as well as for global success and overall participant satisfaction (all P < .001). Digital UV fluorescence photography demonstrated a rapid reduction in Propionibacterium acnes in the A/BPO with doxycycline group, particularly within the first 4 weeks. These findings provide evidence on the efficacy of combining A/BPO and the oral antibiotic doxycycline in the treatment of severe acne vulgaris.
Levine RM, Rasmussen JE.
Intralesional corticosteroids in the treatment of nodulocystic acne.
Arch Dermatol. 1983 Jun;119(6):480-1.
Abstract/Text
We evaluated the effectiveness of intralesional injections of corticosteroids in the therapy for nodulocystic acne. Triamcinolone acetonide at a concentration of 0.63 mg/mL was as efficacious as a higher concentration of 2.5 mg/mL. Betamethasone phosphate had little, if any, effect on nodulocystic acne lesions at concentrations of 3.0, 1.5, and 0.75 mg/mL, when compared with saline controls.
Layton AM, Yip J, Cunliffe WJ.
A comparison of intralesional triamcinolone and cryosurgery in the treatment of acne keloids.
Br J Dermatol. 1994 Apr;130(4):498-501. doi: 10.1111/j.1365-2133.1994.tb03385.x.
Abstract/Text
Keloid scarring presents a difficult therapeutic problem. It is a recognized sequel to acne vulgaris, and may be extensive and disfiguring. The data from this double-blind study, in which intralesional triamcinolone or cryosurgery were used as treatment for keloids, demonstrate that by treating early, and in particular vascular, keloids with the latter, 85% will show a moderate to good response in terms of flattening. Treatment with intralesional triamcinolone was also beneficial, but the response to cryosurgery was significantly better in early, vascular lesions.
Thiboutot DM, Shalita AR, Yamauchi PS, Dawson C, Kerrouche N, Arsonnaud S, Kang S.
Adapalene gel, 0.1%, as maintenance therapy for acne vulgaris: a randomized, controlled, investigator-blind follow-up of a recent combination study.
Arch Dermatol. 2006 May;142(5):597-602. doi: 10.1001/archderm.142.5.597.
Abstract/Text
OBJECTIVE: To assess the maintenance effect of adapalene gel, 0.1%, relative to gel vehicle in subjects successfully treated in a previous 12-week study of adapalene-doxycycline, 100 mg, combination therapy.
DESIGN: Multicenter, investigator-blind, randomized, controlled study.
SETTING: Thirty-four US centers.
SUBJECTS: A total of 253 subjects with severe acne vulgaris who showed at least moderate improvement from baseline (50% improvement from baseline) when treated with either adapalene plus doxycycline or doxycycline plus gel vehicle in a previous 12-week study.
INTERVENTIONS: Subjects were randomized to receive adapalene gel, 0.1%, or gel vehicle once daily for 16 weeks.
MAIN OUTCOME MEASURES: Efficacy and safety criteria included maintenance rate (subjects maintaining at least 50% improvement in lesion counts from previous therapy), lesion counts (total, inflammatory, and noninflammatory), global severity assessment, cutaneous tolerability, and adverse events.
RESULTS: Adapalene maintenance therapy resulted in significantly larger maintenance rates (75% vs 54%; P<.001) and significantly lower lesion counts (total [P = .005], inflammatory [P = .01], and noninflammatory [P = .02]) compared with gel vehicle. Adapalene was safe and well tolerated in this study. Conclusion This study demonstrates a clinical benefit of continued treatment with adapalene gel, 0.1%, as a maintenance therapy for acne.
Zhang JZ, Li LF, Tu YT, Zheng J.
A successful maintenance approach in inflammatory acne with adapalene gel 0.1% after an initial treatment in combination with clindamycin topical solution 1% or after monotherapy with clindamycin topical solution 1%.
J Dermatolog Treat. 2004 Dec;15(6):372-8. doi: 10.1080/09546630410021702.
Abstract/Text
METHODS: A total of 300 acne subjects entered this multicentre, randomized, investigator-blinded study comparing the efficacy and safety of adapalene gel 0.1% plus clindamycin topical solution 1% versus clindamycin topical solution 1% alone. In the second part of the study (weeks 12-24), completed by 241 subjects, the efficacy and safety of adapalene gel 0.1% alone as a maintenance therapy was investigated.
RESULTS: A statistically significant greater reduction was observed from week 4 until week 12 in total lesion counts and from week 8 on for inflammatory and non-inflammatory lesion counts during the initial treatment for combination therapy compared with monotherapy. Results at week 24 for the reduction in all lesion counts during the maintenance phase were statistically significant in favour of adapalene (41.6%) compared with an increase for all lesion counts in the control group (92.1%). Adapalene alone or in combination with clindamycin topical solution was well tolerated. Few adverse events occurred, all of them during the initial treatment phase. Most of these local events were mild or moderate.
CONCLUSION: The present study confirmed the importance of a maintenance therapy after a successful initial treatment and underlined the benefit of a combination therapy with a topical retinoid such as adapalene and a topical antibiotic in the treatment of inflammatory acne.
Kawashima M, Harada S, Andres P, Miyachi Y: One-year efficacy and safety of adapalene gel 0.1％gel in Japanese patients with acnevulgaris．Skin Research 2007; 6(5):504-512（エビデンスレベルIII）.
