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Treatment of Psoriatic Arthritis and Rheumatoid Arthritis with Disease Modifying Drugs — Comparison of Drugs and Adverse Reactions

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Treatment of Psoriatic Arthritis and Rheumatoid Arthritis with Disease Modifying Drugs — Comparison of Drugs and Adverse Reactions Treatment of Psoriatic Arthritis and Rheumatoid Arthritis with Disease Modifying Drugs — Comparison of Drugs and Adverse Reactions PHILIP S. HELLIWELL and WILLIAM J. TAYLOR for the CASPAR Study Group ABSTRACT. Objective. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory diseases of the musculoskeletal system. Although it seems likely that these conditions have a different pathogene- sis, the drugs used to treat them are the same. Our study used a cross-sectional clinical database to com- pare drug use and side-effect profile in these 2 diseases. Methods. The CASPAR study collected data on 588 patients with PsA and 536 controls, 70% of whom had RA. Data on disease modifying drug treatments used over the whole illness were recorded, togeth- er with their outcomes, including adverse events, for RA and PsA. Results. For both diseases methotrexate (MTX) was the most frequently used disease modifying drug (39% of patients with PsA, 30% with RA), with over 70% of patients in both diseases still taking the drug. Other drugs were used with the following frequencies in PsA and RA, respectively: sulfasalazine 22%/13%, gold salts 7%/11%, antimalarial drugs 5%/14%, corticosteroids 10%/17%, and anti-tumor necrosis factor (TNF) drugs 6%/5%. Compared to RA, cyclosporine and anti-TNF agents were less like- ly to be ineffective in PsA. Compared to RA, subjects with PsA were less likely to be taking MTX and more likely to be taking anti-TNF agents. Hepatotoxicity with MTX was more common in PsA, and pul- monary toxicity with MTX was found more often in RA. Conclusion. These data provide insight into prescribing patterns of disease modifying drugs in RA and PsA in a large international cohort, together with the differential adverse events of these drugs between these diseases. (First Release Jan 15 2008; J Rheumatol 2008;35:472–6) Key Indexing Terms: PSORIATIC ARTHRITIS RHEUMATOID ARTHRITIS ADVERSE EFFECTS DISEASE MODIFYING DRUGS TREATMENT ANTI-TUMOR NECROSIS FACTOR DRUGS Psoriatic arthritis (PsA) is an inflammatory arthritis associat- for the more recently introduced pharmaceuticals, lefluno- ed with psoriasis. Recent developments have seen the propos- mide and anti-tumor necrosis factor (TNF) drugs. Low-dose al of new internationally agreed classification criteria1 and a weekly oral or systemic methotrexate (MTX) is widely used review of evidence for the efficacy of disease modifying to treat PsA, yet the evidence base for the use of it is poor, drugs2. Consistent with the recent upsurge in interest in this graded as at best level B for polyarticular disease in the recent condition, the best quality evidence for treatment efficacy is review3. Further, treatment trials are constrained in ways that may detract from the use of the drug in everyday practice — From the Academic Unit of Musculoskeletal and Rehabilitation Medicine, patients entered into trials are often a very select group with University of Leeds, Leeds, UK; and the Rehabilitation Teaching and 4 Research Unit, Department of Medicine, Wellington School of Medicine little comorbidity , which confounds extrapolation of drug use and Health Sciences, University of Otago, Wellington, New Zealand. to a wide spectrum of patients. Supported by the European League Against Rheumatism, Barnsley District There is also the question of the differential adverse event NHS Trust, Groote Schuur Hospital, Cape Town, South Africa; Department of Medical Sciences, University Hospital, Uppsala, Sweden; profile for each of the drugs used to treat PsA and rheumatoid Krembil Foundation; St. Vincent’s University Hospital Radiology arthritis (RA). For example, hepatotoxicity with MTX is Department, Dublin, Ireland; Inkosi Albert Luthuli Central Hospital, regarded as more frequent when this drug is used to treat pso- Durban, South Africa; El Ayachi Hospital, Salé, Morocco; National 5 Psoriasis Foundation, USA; The Foundation for Scientific Research of the riasis and PsA than when it is used in RA . The reverse is true Belgian Society of Rheumatology; and Arthritis New Zealand. Dr. Taylor for pulmonary complications of MTX use, which may reflect was supported by a Dorothy Eden Fellowship, Arthritis New Zealand. the more frequent involvement of the lung in RA6. The pub- P.S. Helliwell, MD, PhD, Academic Unit of Musculoskeletal and lished data to support these assertions are relatively limited Rehabilitation Medicine, University of Leeds; W.J. Taylor, MBChB, PhD, FRACP, FAFRM, Rehabilitation Teaching and Research Unit, Department and lack appropriate control of possible confounding factors of Medicine, Wellington School of Medicine and Health Sciences, such as preexisting lung disease and alcohol consumption. University of Otago. The CASPAR study (ClASsification criteria for Psoriatic Address reprint requests to Dr. P. Helliwell, Academic Unit of Musculoskeletal and Rehabilitation Medicine, University of Leeds, 36 ARthritis) collected clinical, radiological, and laboratory data Clarendon Road, Leeds LS2 9NZ, UK. E-mail: [email protected] on 588 patients with physician-diagnosed PsA and 536 con- Accepted for publication October 24, 2007. trols with other inflammatory arthritis, 70% of whom had Personal non-commercial use only. The Journal of Rheumatology Copyright © 2008. All rights reserved. 472 The Journal of Rheumatology 2008; 35:3 Downloaded on September 23, 2021 from www.jrheum.org RA1. The CASPAR study also provided an opportunity to determine the association of disease and drug with side-effect. Much of this review the use of disease modifying drugs across a wide spec- analysis was invalid because of sparse data, so the statistical analysis concen- trated on MTX. trum of patients from an international cohort. The aim of this study was, therefore, to examine the disease modifying drugs RESULTS used and their efficacy and adverse event profile in patients Data were collected prospectively from 588 consecutive clin- with PsA, and to compare these with drugs used in patients ic attendees with PsA and 536 control patients, as described. diagnosed with RA. Control patients had RA (n = 384), ankylosing spondylitis (n = 72), undifferentiated arthritis (n = 38), connective tissue dis- MATERIALS AND METHODS orders (n = 14), and other diseases (n = 28). Subsequent analy- Ethical approval for this study was obtained at each of the contributing study sites. Consecutive clinic attendees with physician-diagnosed PsA were sis focused on drug outcomes in patients with PsA and RA enrolled into the study by 30 rheumatology clinics in 13 countries. Controls only. The disease duration for PsA and RA was similar, but were the next clinic attendee with inflammatory arthritis. It was prespecified patients with PsA were younger and more likely to be male that at least 50% of controls were to have RA to reflect the disease distri- than patients with RA. Demographic variables and further bution seen in normal rheumatological practice. Data were recorded onto clinical data are given in Table 2. standardized forms and included demographic and clinical data as described1. In addition, data on disease modifying treatment were recorded. Psoriatic arthritis. Table 3 details the drugs used in PsA, by The sequence (first drug used, second drug, and so on) and outcome sequence and drug. No drug therapy was recorded for 70 (whether still taking, or if discontinued, giving the reason why) were (12%) cases. Across all sequences MTX was the most fre- recorded for each drug, to a maximum of 7, including drug combinations. Details of start and stop dates and the indications for each drug were not quently used drug (39% of all drugs used), followed by sul- recorded on the proforma, but as the data were recorded by rheumatologists, fasalazine (22%). The proportion of patients receiving anti- it was assumed that the disease modifying treatment was given for the TNF drugs increased with each sequence, reflecting the time arthritis rather than the skin. over which these patients had been treated and the use of these Data forms were sent to the coordinating site, where they were entered into an SPSS database. Data entry accuracy was checked on a random sample drugs after “conventional” disease modifying drugs. of 10% of cases and the appropriateness of the diagnostic label was checked In the 404 patients where drugs were still being taken, drug on a further sample of 10% by a quality control committee. combinations were used in 92 (23%) cases. In the majority of Statistical analysis. The relationship between disease, drug, and outcome cases 2 drugs were combined, the drug combinations most fre- (Table 1) was examined using Loglinear analysis in SPSS v 15.0. Two models quently used being MTX/sulfasalazine (33 cases), were examined. First, a log-linear model that predicted the numbers as dis- MTX/steroids (22 cases), and MTX/anti-TNF (16 cases). In 9 played in the cells of a table of outcome by drug by disease, using this to deter- mine the association of disease and treatment with outcome. Four categories cases, triple therapy was employed — MTX was used in all of were used for outcome: adverse effect, ineffective, remission, and still taking. these in various combinations that also included cyclosporine, The saturated model, that is, with all main effects, 2-way interactions, and the sulfasalazine, antimalarials, and anti-TNF drugs. 3-way interaction, was fitted using a test of partial associations for the effect Rheumatoid arthritis. Table 4 details the drugs used in RA, by of components of the model. Second, a
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