M E Roberts, V Wright, A G Hill, A C Mehra
Psoriatic arthritis. Follow-up study.
Ann Rheum Dis. 1976 Jun;35(3):206-12.
Abstract/Text
227 patients with psoriasis and various forms of arthritis have been kept under review. Psoriasis and inflammatory arthropathy was present in 168 patients, of whom 94 have been followed up for more than 10 years. An arthritis indistinguishable from rheumatoid disease was present in 78%, distal joint arthritis in 16-6%, and deforming arthritis in 4-8%. There was a female predominance in the sex ratio of patients, although males predominated in the distal joint group (male:female 1-5:1). The peak age of onset was between 36 and 45 years, although in the deforming group the arthritis began before the age of 20 three times as commonly as it did in the indistinguishable group. Onset was acute in nearly half of the patients. At onset the distal joints were affected in one-third of the distal joint group. A synchronous onset of skin and joint changes was uncommon. Skin lesions usually preceded the arthritis but occurred after onset in 16%. Apart from in the deforming group, the arthritis was mild, judged by the number of admissions to hospital for treatment of the joint disease, and the time off work. Deterioration clinically and radiographically occurred in only a small portion of the distal joint and indistinguishable groups. Antimalarial drugs have been used in 7 patients, with deterioration of the skin condition in 4. Uveitis occurred particularly in the men of all three groups, but was most frequent in those with deforming arthritis. A family history of psoriasis was obtained in 26% of first-degree relatives and 13% of second-degree relatives. A history of polyarthritis was most common in patients in the deforming group. The sheep cell agglutination test was negative in the majority, but was positive in 16% of the indistinguishable group, fluctuating in a further 10%. A small number of joints only deteriorated radiographically (10% of the distal and indistinguishable groups). The men in the distal group showed greater radiographic changes and more deterioration in the terminal interphalangeal joints of the fingers than the women. Similarly they showed more deterioration of the metatarsophalangeal joints than the women. 18 patients died, one with gastric haemorrhage resulting from treatment of exfoliative psoriasis with immunosuppressive therapy, and 2 from bronchopneumonia thought to be related to immobility caused by the arthritis.
M R Cohen, D J Reda, D O Clegg
Baseline relationships between psoriasis and psoriatic arthritis: analysis of 221 patients with active psoriatic arthritis. Department of Veterans Affairs Cooperative Study Group on Seronegative Spondyloarthropathies.
J Rheumatol. 1999 Aug;26(8):1752-6.
Abstract/Text
OBJECTIVE: To determine differences in disease onset, extent, and manifestations of psoriasis among patients with active, inflammatory psoriatic arthritis (PsA), and to examine relationships that may exist between psoriasis and PsA.
METHODS: Baseline demographic, clinical, and laboratory data were analyzed from 221 patients enrolled in a multicenter cooperative study, and relationships between measures of psoriasis and PsA were determined.
RESULTS: Mean percentage of body surface area (BSA) affected by psoriasis was modest (12+/-17), and mean severity of erythema, induration, and scaling was moderate (4.9+/-2.1 on a 0-9 scale). Spanish Americans tended to have a higher mean percentage of BSA (18.5%) than Caucasians (11%; p = 0.067), as well as higher target lesion severity (5.55 vs. 4.84; p = 0.077). Patients with psoriatic nail disease (180/221, 81%) had significantly greater number of involved distal interphalangeal (DIP) joints (p = 0.004). There were no other significant associations of skin pattern or regional involvement with PsA.
CONCLUSION: Patients with active PsA have generally mild skin disease, and baseline relationships between psoriasis and PsA tend to be weak except for nail involvement and DIP joint activity.
L Williamson, N Dalbeth, J L Dockerty, B C Gee, R Weatherall, B P Wordsworth
Extended report: nail disease in psoriatic arthritis--clinically important, potentially treatable and often overlooked.
Rheumatology (Oxford). 2004 Jun;43(6):790-4. doi: 10.1093/rheumatology/keh198. Epub 2004 Apr 27.
Abstract/Text
OBJECTIVES: To examine the relationship between the severity of nail disease and characteristics of psoriatic arthritis (PsA). We also wished to assess the clinical management of nail disease in patients with PsA.
METHODS: We studied 69 patients with PsA at two visits. On the first visit, a rheumatology assessment of joint, skin and nail disease was made. On the second visit, a detailed dermatology assessment of skin and nails was made. Nail disease was analysed using a 20-nail psoriasis nail severity score (PNSS).
RESULTS: There were 57 (83%) patients with clinical evidence of psoriatic nail disease. Although 66 (96%) patients had been treated for skin disease, only one (1%) had received any treatment for nail disease. Severe nail disease measured by the PNSS correlated with severe skin psoriasis as indicated by the percentage of body surface area affected by psoriasis (r = 0.34, P = 0.004) and physician global assessment of psoriasis (r = 0.45, P<0.001). Patients with distal interphalangeal (DIP) joint disease had higher PNSS scores (P = 0.03). The PNSS was also associated with unremitting and progressive arthritis (P<0.001), and correlated with Stanford health assessment questionnaire (HAQ) (r = 0.34, P = 0.004), depression (r = 0.39, P<0.001) and anxiety (r = 0.34, P = 0.004) scores. Compared with dermatology assessment, the rheumatology examination of nail disease had a positive predictive value of 84% and negative predictive value of 83%.
CONCLUSIONS: In patients with PsA, the severity of nail disease correlates with indicators of severity of both skin and joint disease. Although rheumatologists can adequately screen for nail disease, the management of this aspect of PsA is often overlooked.
D D Gladman, K A Anhorn, R K Schachter, H Mervart
HLA antigens in psoriatic arthritis.
J Rheumatol. 1986 Jun;13(3):586-92.
Abstract/Text
HLA antigen frequencies were studied in 158 patients with psoriatic arthritis, and compared to those of 101 patients with uncomplicated psoriasis and 243 healthy controls. The HLA antigens B16, B17, B27, B39 and Cw6 were associated with psoriatic arthritis. No associations between DR antigens and psoriatic arthritis were demonstrated. However, the subset of patients with rheumatoid-like arthritis demonstrated an increase in DR4. Uncomplicated psoriasis patients had higher frequencies of B17, Cw6 and DR7 than patients with psoriatic arthritis, while B7 and B27 correlated with development of arthritis. HLA-B27, Cw2 and DRw52 were associated with back involvement, whereas B38 and B39 were associated with polyarthritis. HLA-B7, B13 and DR7 correlated with milder disease in patients with psoriatic arthritis.
P Rahman, J T Elder
Genetic epidemiology of psoriasis and psoriatic arthritis.
Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii37-9; discussion ii40-1. doi: 10.1136/ard.2004.030775.
Abstract/Text
Psoriasis and psoriatic arthritis (PsA) are interrelated disorders, as most patients with PsA also have psoriasis. Thus it is not surprising that epidemiological and immunogenetic studies have uncovered important links between these two disorders. Both disorders are highly heritable, and the prevalence of psoriasis is 19 times higher among first degree relatives of probands with PsA compared with the general population. Multiple human leucocyte antigen (HLA) associations are shared between psoriasis and PsA, though the magnitudes of these associations differ between the diseases. Genome-wide linkage studies have noted overlapping regions of significance for these two disorders within and outside the major histocompatibility complex (MHC) region. Thus, exploration of the genetic basis of psoriasis will likely strengthen the contention of an underlying genetic susceptibility for PsA and vice versa.
O B Pedersen, A J Svendsen, L Ejstrup, A Skytthe, P Junker
On the heritability of psoriatic arthritis. Disease concordance among monozygotic and dizygotic twins.
Ann Rheum Dis. 2008 Oct;67(10):1417-21. doi: 10.1136/ard.2007.078428. Epub 2008 Jan 24.
Abstract/Text
OBJECTIVE: A nationwide unselected twin population to estimate the relative importance of genetic and environmental effectors in the aetiopathogenesis of psoriatic arthritis (PsA).
METHODS: The study comprised three Danish nationwide twin cohorts. In 1994 and 2002 a total of 37 388 and 46 418 Danish twin individuals respectively were asked by questionnaire if they had PsA. Twins reporting PsA were invited to participate in a clinical examination. Patients were classified according to the Moll and Wright and the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria. Heritability was estimated by probandwise concordance rates and variance component analysis.
RESULTS: 228 twin individuals reported PsA. Following diagnostic validation in 164 (70%), 50 probands were diagnosed with PsA according to the Moll and Wright criteria. Five of their co-twins were either dead, had emigrated, or did not participate in the twin study and nine did not respond, resulting in 36 complete pairs. A total of one of 10 monozygotic pairs and one of 26 dizygotic pairs were concordant for PsA, yielding a 6.2% difference in proportions (95% CI: -11%, 37%). Five of 10 monozygotic pairs and four of 26 dizygotic pairs were concordant for psoriatic skin disease implying a 35% difference (95% CI: 2%, 60%, p<0.05).
CONCLUSIONS: This first twin study on PsA confirms that genes are important in the causation of psoriatic skin disease. Despite the limited statistical power, the almost identical concordance rates for PsA in monozygotic and dizygotic twins stresses the importance of the continued search for non-genetic effectors in PsA.
A Myers, L J Kay, S A Lynch, D J Walker
Recurrence risk for psoriasis and psoriatic arthritis within sibships.
Rheumatology (Oxford). 2005 Jun;44(6):773-6. doi: 10.1093/rheumatology/keh589. Epub 2005 Mar 9.
Abstract/Text
OBJECTIVE: To quantify the frequency of siblings of patients with psoriatic arthritis (PsA) having psoriasis and/or inflammatory arthritis. To describe the similarity or otherwise of patterns of arthritis in siblings.
METHODS: Available and consenting index cases with PsA and one or more siblings living locally were assessed. Mean sibling concordance rates and Weinberg's segregation analysis were calculated. Heritability was also estimated. To assess whether the same type of arthritis occurred within the same sibship, the dually affected sibships were then classified for type of arthritis according to methods suggested by Moll, Helliwell, Veale and McGonagle.
RESULTS: Eighty index cases and 112 siblings were assessed. The median age of index cases was 49 yr (range 24-80 yr) and for siblings 46 yr (range 18-79 yr). The concordance rate for all types of PsA was 14% (9% if enthesitis is excluded) and for psoriasis 21%. There was no difference in the two methods used to calculate concordance rates. Sixteen dually affected sib pairs were found. Four of the 16 sibships (25%) had the same pattern of joint involvement (Moll and Wright classification). The most frequent pattern seen was joint involvement identical to rheumatoid arthritis (3/5). The most common symptom in affected siblings was enthesitis (approximately 5%). When the dually affected sibships were analysed using the other classifications, the simpler the classification the greater the concordance for joint pattern.
CONCLUSION: The concordance for psoriasis is greater than for PsA, but the concordance rate for PsA was similar to that in HLA identical siblings with rheumatoid arthritis. There was discordance in pattern of arthritis for most sib pairs. There is no support for the use of more complex classifications of PsA.
William Taylor, Dafna Gladman, Philip Helliwell, Antonio Marchesoni, Philip Mease, Herman Mielants, CASPAR Study Group
Classification criteria for psoriatic arthritis: development of new criteria from a large international study.
Arthritis Rheum. 2006 Aug;54(8):2665-73. doi: 10.1002/art.21972.
Abstract/Text
OBJECTIVE: To compare the accuracy of existing classification criteria for the diagnosis of psoriatic arthritis (PsA) and to construct new criteria from observed data.
METHODS: Data were collected prospectively from consecutive clinic attendees with PsA and other inflammatory arthropathies. Subjects were classified by each of 7 criteria. Sensitivity and specificity were compared using conditional logistic regression analysis. Latent class analysis was used to calculate criteria accuracy in order to confirm the validity of clinical diagnosis as the gold standard definition of "case"-ness. Classification and Regression Trees methodology and logistic regression were used to identify items for new criteria, which were then constructed using a receiver operating characteristic curve.
RESULTS: Data were collected on 588 cases and 536 controls with rheumatoid arthritis (n = 384), ankylosing spondylitis (n = 72), undifferentiated arthritis (n = 38), connective tissue disorders (n = 14), and other diseases (n = 28). The specificity of each set of criteria was high. The sensitivity of the Vasey and Espinoza method (0.97) was similar to that of the method of McGonagle et al (0.98) and greater than that of the methods of Bennett (0.44), Moll and Wright (0.91), the European Spondylarthropathy Study Group (0.74), and Gladman et al (0.91). The CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria consisted of established inflammatory articular disease with at least 3 points from the following features: current psoriasis (assigned a score of 2; all other features were assigned a score of 1), a history of psoriasis (unless current psoriasis was present), a family history of psoriasis (unless current psoriasis was present or there was a history of psoriasis), dactylitis, juxtaarticular new bone formation, rheumatoid factor negativity, and nail dystrophy. These criteria were more specific (0.987 versus 0.960) but less sensitive (0.914 versus 0.972) than those of Vasey and Espinoza.
CONCLUSION: The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria.
C T Ritchlin, A Kavanaugh, D D Gladman, P J Mease, P Helliwell, W-H Boehncke, K de Vlam, D Fiorentino, O Fitzgerald, A B Gottlieb, N J McHugh, P Nash, A A Qureshi, E R Soriano, W J Taylor, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)
Treatment recommendations for psoriatic arthritis.
Ann Rheum Dis. 2009 Sep;68(9):1387-94. doi: 10.1136/ard.2008.094946. Epub 2008 Oct 24.
Abstract/Text
OBJECTIVE: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion.
METHODS: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire.
RESULTS: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective.
CONCLUSIONS: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.
S R Johnson, C T Schentag, D D Gladman
Autoantibodies in biological agent naive patients with psoriatic arthritis.
Ann Rheum Dis. 2005 May;64(5):770-2. doi: 10.1136/ard.2004.031286.
Abstract/Text
BACKGROUND: Anti-tumour necrosis factor alpha (anti-TNFalpha) treatment may be associated with the production of autoantibodies, including lupus-specific autoantibodies.
OBJECTIVE: To investigate the prevalence of autoantibodies in biological agent naive patients with psoriatic arthritis (PsA).
METHODS: 94 consecutive, prospectively collected, biological agent naive patients with PsA at the University of Toronto PsA clinic underwent clinical and laboratory assessment. Disease activity was assessed by the number of actively inflamed joints, and the Psoriasis Activity and Severity Index (PASI) score. Antinuclear antibodies (ANA), rheumatoid factor (RF), double stranded DNA (dsDNA), Ro, La, Smith, and RNP were tested. Descriptive statistics and non-parametric tests were used to analyse the data.
RESULTS: 44/94 (47%) patients with PsA were ANA positive (>/=1/40); 13/94 (14%) had a clinically significant titre of >/=1/80. Three per cent had dsDNA antibodies, 2% had RF and anti-Ro antibodies, 1% had anti-RNP antibodies, and none had anti-La or anti-Smith antibodies.
CONCLUSIONS: The background prevalence of ANA >/=1/80 in patients with PsA was 14%, with very few patients having specific lupus antibodies. This should serve as a baseline figure for the frequency of autoantibodies in biological agent naive patients with PsA for studies of the use of anti-TNFalpha agents.
G M Alenius, E Berglin, S Rantapää Dahlqvist
Antibodies against cyclic citrullinated peptide (CCP) in psoriatic patients with or without joint inflammation.
Ann Rheum Dis. 2006 Mar;65(3):398-400. doi: 10.1136/ard.2005.040998. Epub 2005 Aug 11.
Abstract/Text
OBJECTIVE: To compare the prevalence of anti-CCP antibodies in psoriatic patients with and without joint inflammation, patients with early RA, and controls.
METHODS: Anti-CCP antibodies (cut off level 5 U/ml) were measured in 160 patients with psoriatic arthritis (PsA), 146 patients with psoriasis but no arthritic disease, 101 patients with early RA, and 102 healthy controls by ELISA.
RESULTS: 11 (7%) patients with PsA, 75 (74%) patients with early RA, 2 (2%) healthy controls (2%), and 1 (0.7%) patient with psoriasis without arthritis had anti-CCP antibodies above the cut off level. The presence of anti-CCP antibodies was not related to radiological changes and/or deformity and functional impairment in PsA. 8/11 patients with PsA and anti-CCP antibodies had a polyarthritic disease, and all fulfilled the ACR criteria for RA at 4 year follow up. Five of these 8 patients also had manifestations such as dactylitis, DIP involvement, radiological changes associated with PsA, and/or enthesitis. In multiple logistic regression analysis with polyarthritis as the dependent variable, anti-CCP antibodies and rheumatoid factor significantly distinguished RA from PsA.
CONCLUSIONS: Anti-CCP antibodies were more prevalent in patients with PsA than in patients with psoriasis without arthritis, but less prevalent than in patients with early RA. Patients with PsA positive for anti-CCP antibodies more often had polyarthritic disease, but the presence of anti-CCP antibodies did not relate to radiological changes and/or deformity and functional impairment.
B Vander Cruyssen, I E A Hoffman, H Zmierczak, M Van den Berghe, E Kruithof, L De Rycke, H Mielants, E M Veys, D Baeten, F De Keyser
Anti-citrullinated peptide antibodies may occur in patients with psoriatic arthritis.
Ann Rheum Dis. 2005 Aug;64(8):1145-9. doi: 10.1136/ard.2004.032177. Epub 2005 Feb 4.
Abstract/Text
BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered highly specific markers of rheumatoid arthritis. Despite the high specificity of the test, anti-CCP antibodies have also been observed in psoriatic arthritis.
OBJECTIVE: To determine the frequency of anti-CCP antibodies in psoriatic arthritis and to describe the clinical characteristics of such patients.
METHODS: Serum samples from 192 patients with psoriatic arthritis were analysed for anti-CCP antibodies. A previously defined cut off point was applied at a specificity level of > or =98.5% (42 U/ml). Antibodies against pepA and pepB (two synthetic citrullinated peptides) were determined on samples containing anti-CCP antibodies by line immune assay. The swollen joint count and the numbers of affected joints (present or past) were recorded. Clinical features were noted and if available radiographs of hands and feet were scored for erosions. Rheumatoid factor was determined in all samples.
RESULTS: Anti-CCP antibodies were found in 15 patients (7.8%); 13 of 15 anti-CCP2 positive samples were also positive for anti-pepA or pepB antibodies. The prevalence of anti-CCP antibodies was higher than expected in view of the highly specific cut off applied in the test. Detailed analysis of the clinical and radiological features makes it improbable that the high prevalence of anti-CCP antibodies resulted solely from concomitant psoriasis and rheumatoid arthritis or from misclassification.
CONCLUSIONS: Anti-CCP antibodies may be present in patients with psoriatic arthritis. Although some of the present cohort could have had psoriasis with concomitant rheumatoid arthritis, a proportion at least had the typical characteristics of psoriatic arthritis as the primary diagnosis.
L Gossec, J S Smolen, C Gaujoux-Viala, Z Ash, H Marzo-Ortega, D van der Heijde, O FitzGerald, D Aletaha, P Balint, D Boumpas, J Braun, F C Breedveld, G Burmester, J D Cañete, M de Wit, H Dagfinrud, K de Vlam, M Dougados, P Helliwell, A Kavanaugh, T K Kvien, R Landewé, T Luger, M Maccarone, D McGonagle, N McHugh, I B McInnes, C Ritchlin, J Sieper, P P Tak, G Valesini, J Vencovsky, K L Winthrop, A Zink, P Emery, European League Against Rheumatism
European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies.
Ann Rheum Dis. 2012 Jan;71(1):4-12. doi: 10.1136/annrheumdis-2011-200350. Epub 2011 Sep 27.
Abstract/Text
BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD).
METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement.
RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined.
CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.
Zoe Ash, Cécile Gaujoux-Viala, Laure Gossec, Elizabeth M A Hensor, Oliver FitzGerald, Kevin Winthrop, Désirée van der Heijde, Paul Emery, Josef S Smolen, Helena Marzo-Ortega
A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis.
Ann Rheum Dis. 2012 Mar;71(3):319-26. doi: 10.1136/ard.2011.150995. Epub 2011 Jul 28.
Abstract/Text
OBJECTIVES: To review the available evidence for the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and biological drug therapies for the different clinical manifestations of psoriatic arthritis (PsA) in order to provide data for the development of treatment recommendations by the European League Against Rheumatism (EULAR) taskforce.
METHODS: A systematic literature review (SLR) of available treatments for PsA was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE) by two working groups formed within the EULAR taskforce. This comprised a comprehensive sample of rheumatologists, dermatologists, epidemiologists and patients. The available evidence was reviewed for NSAIDs, synthetic disease modifying antirheumatic drugs (DMARDs), local and systemic corticosteroids and biologic drugs. All articles and abstracts published between 1962 and January 2010 were reviewed and considered and a meta-analysis of data on biological therapies was performed.
RESULTS: While little data are available on NSAIDs, glucocorticoids and synthetic DMARDs, the available evidence suggests an acceptable efficacy and safety profile of both NSAIDs and synthetic DMARDs (methotrexate, cyclosporine A, sulfasalazine and leflunomide) in PsA. More evidence is available (level 1B) supporting the efficacy of anti-tumour necrosis factor (anti-TNF) agents (adalimumab, etanercept, golimumab and infliximab) in treating the signs and symptoms of PsA as well as reducing radiographic progression. Registry data show no new safety concerns, although the numbers studied to date are relatively small.
CONCLUSIONS: This SLR reveals some evidence to support the use of NSAIDs and synthetic DMARDs and good evidence for the efficacy of anti-TNF therapy in PsA.
Alan J Kivitz, Luis R Espinoza, Yvonne R Sherrer, Maria Liu-Dumaw, Christine R West
A comparison of the efficacy and safety of celecoxib 200 mg and celecoxib 400 mg once daily in treating the signs and symptoms of psoriatic arthritis.
Semin Arthritis Rheum. 2007 Dec;37(3):164-73. doi: 10.1016/j.semarthrit.2007.03.004. Epub 2007 Jun 14.
Abstract/Text
OBJECTIVE: To evaluate the efficacy of the cyclooxygenase-2 selective inhibitor celecoxib in treating patients with psoriatic arthritis (PsA) in flare.
METHODS: This 12-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study compared the efficacy and safety of celecoxib 400 mg (n=201) or celecoxib 200 mg (n=213) once daily (qd) with placebo (n=194) in treating the signs and symptoms of PsA in flare. The primary efficacy measure was the number of patients responding to treatment according to the American College of Rheumatology Responders Index 20% (ACR-20) at week 12. Efficacy and safety were assessed for all randomized patients who received at least 1 dose of study medication.
RESULTS: At the week-12 primary endpoint, approximately 50% of patients in each treatment group were responders according to the ACR-20 criteria, and no statistically significant treatment differences between treatment groups were observed. However, at week 2, the ACR-20 response rates for the celecoxib 400 mg (49%) and 200 mg (39%) groups were significantly higher than for the placebo group (28%) (P<0.001 and P=0.016, respectively). Within the celecoxib 400 mg group, ACR-20 response rates were similar at weeks 2, 6 (46%), and 12 (49%). In contrast, in the celecoxib 200 mg and placebo treatment groups, ACR-20 response rates increased 7 and 16%, respectively, from week 2 to week 6, and remained relatively unchanged from week 6 to week 12. There were no statistically significant differences in ACR-20 response rates between the celecoxib 400 mg and 200 mg groups at any time point. Treatment with celecoxib 200 and 400 mg qd was statistically superior to placebo treatment at weeks 2 and 6 for Patient's Assessment of Arthritis Pain. Both doses of celecoxib were well tolerated.
CONCLUSIONS: Celecoxib 400 mg and 200 mg qd were efficacious and well tolerated in treating the signs and symptoms of PsA in flare after 2 weeks of treatment. However, although the clinical effects of celecoxib 400 mg and 200 mg qd were observed for 12 weeks, there was a high placebo response at these time points, and there were no differences relative to placebo treatment at week 12.
Q E Whiting-O'Keefe, K H Fye, K D Sack
Methotrexate and histologic hepatic abnormalities: a meta-analysis.
Am J Med. 1991 Jun;90(6):711-6.
Abstract/Text
STUDY OBJECTIVE: To determine the risk of liver toxicity from the long-term administration of methotrexate in patients with rheumatoid arthritis or psoriatic arthritis.
DESIGN: A meta-analysis of 15 studies examining the relationship between long-term, low-dose methotrexate administration and biopsy evidence of liver fibrosis.
PATIENTS: A total of 636 patients from 15 studies.
RESULTS: The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9% (95% confidence intervals 24.3 to 31.6). The rate of progression of liver disease in the 15 studies was associated with the cumulative dose of methotrexate (p = 0.01). Patients on average had a 6.7% (95% confidence intervals 2.1 to 11.4) chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% (95% confidence intervals 3.5 to 7.0). The development of advanced histologic changes was not associated with the cumulative dose of methotrexate (p = 0.08). Patients who according to their history were heavy drinkers (at least 100 g of alcohol per week) were more likely to have advanced changes on liver biopsy (17.8% versus 4.5%, p = 0.0003) and to show histologic progression (73.3% versus 25.9%, p = 0.0002). Patients with psoriasis were more likely than patients with rheumatoid arthritis to have advanced changes (7.7% versus 2.7%, p = 0.003) and histologic progression (33.1% versus 24.3%, p = 0.02).
CONCLUSIONS: The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity.
J R Curtis, T Beukelman, A Onofrei, S Cassell, J D Greenberg, A Kavanaugh, G Reed, V Strand, J M Kremer
Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide.
Ann Rheum Dis. 2010 Jan;69(1):43-7. doi: 10.1136/ard.2008.101378.
Abstract/Text
INTRODUCTION: Potential hepatotoxicity associated with disease-modifying antirheumatic drugs (DMARDs) requires laboratory monitoring. In patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), the incidence of elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX), leflunomide (LEF) and MTX+LEF versus other DMARDs was examined.
METHODS: Patients with RA and PsA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) initiating DMARDs were identified. Abnormalities were identified when either was 1- or 2-fold times above the upper limits of normal (ULN). Odds ratios (OR) between MTX/LEF dose and elevated ALT/AST enzymes were estimated using generalised estimating equations. Interaction terms for use of MTX+LEF quantified the incremental risk of the combination compared with each individually.
RESULTS: Elevated ALT/AST levels (>1x ULN) occurred in 22%, 17%, 31% and 14% of patients with RA receiving MTX, LEF, MTX+LEF or neither, respectively; elevations were 2.76-fold (95% CI 1.84 to 4.15) more likely in patients with PsA. Elevations >2x ULN occurred in 1-2% of patients on MTX or LEF monotherapy compared with 5% with the combination. After multivariable adjustment and compared with either monotherapy, the combination of MTX and LEF was associated with a greater risk according to MTX dose used as part of the combination: MTX 10-17.5 mg/week, OR 2.91 (95% CI 1.23 to 6.90); MTX > or =20 mg/week, OR 3.98 (95% CI 1.72 to 9.24).
CONCLUSIONS: Abnormal ALT/AST levels developed in 14-35% of patients with RA or PsA initiating DMARD therapy. The risks were incrementally greater in those with PsA and in those receiving MTX (> or =10 mg/day) + LEF. These findings should help inform monitoring for potential hepatotoxicity in these patient populations.
Lihi Eder, Vinod Chandran, Joanna Ueng, Sita Bhella, Ker-Ai Lee, Proton Rahman, Angela Pope, Richard J Cook, Dafna D Gladman
Predictors of response to intra-articular steroid injection in psoriatic arthritis.
Rheumatology (Oxford). 2010 Jul;49(7):1367-73. doi: 10.1093/rheumatology/keq102. Epub 2010 Apr 13.
Abstract/Text
OBJECTIVES: To assess the effectiveness of IA corticosteroid (IAS) injections in PsA and to determine the association between macrophage migration inhibition factor (MIF) gene polymorphism and response to IAS injections.
METHODS: A cohort analysis of PsA patients who were followed prospectively was performed. Clinical response was defined as no tenderness or effusion in the injected joint at 3 months. Relapse was defined as re-occurrence of joint pain or effusion. MIF 173C > G genotyping (rs755622) was performed.
RESULTS: Two hundred and twenty patients with 245 IAS injections were included in the study. The probability of responding at 3 months was 41.6%. Within 12 months, 25.5% of the joints relapsed. Clinical factors that were associated with response included duration of psoriasis [Odds ratio (OR) 1.03] and the use of MTX or anti-TNF agents at the time of injection (OR 2.68). Factors that were associated with relapse included injection into large joints (OR 4.58) and elevated sedimentation rate (OR 15.0), whereas absence of clinical and/or radiographic damage (OR 0.23) and duration of PsA (OR 0.92) reduced risk of relapse. MIF polymorphism was not associated with clinical response, but was associated with relapse (OR 3.2). On multivariate analysis including clinical covariates, the association between MIF polymorphism and relapse was lost.
CONCLUSIONS: IAS injections are effective in PsA. MIF gene polymorphism is associated with relapse. However, this effect is explained by clinical variables that reflect disease activity, suggesting that MIF gene polymorphism influences inflammatory activity.
T Fredriksson, U Pettersson
Severe psoriasis--oral therapy with a new retinoid.
Dermatologica. 1978;157(4):238-44.
Abstract/Text
Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Doses of 25 mg b.i.d., 25 mg t.i.d. and 50 mg b.i.d. were administered orally to 27 patients suffering from severe chronic generalized psoriasis. The clinical efficacy was evaluated by means of a new index, psoriasis area and severity index (PASI) based on severity and area of psoriatic lesions. At doses of 25 mg t.i.d. or 50 mg b.i.d. Ro 10--9359 proved to be an extremely potent antipsoriatic drug. A more than 90% reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4-8 weeks of treatment. This good effect lasted about 5 weeks after treatment. Side effects were frequent, but mostly mild and completely reversible after termination of treatment.
