Limited eVect of sulphasalazine treatment in reactive arthritis. A randomised double blind placebo controlled trial

Objective—To assess the eYcacy and safety of sulphasalazine in reactive arthritis. Methods—Double blind placebo controlled trial of six months duration comparing sulphasalazine 2-3 g per day (n = 37) with matching placebo (n = 42) in adults with active reactive arthritis (age 19-57 years, median 34). Treatment response was evaluated once a month by changes in erythrocyte sedimentation rate (ESR), pain, peripheral arthritis, tender iliosacral joints, entesopathy, extra-articular manifestations, and working ability. Results—15 patients in the sulphasalazine group and eight in the placebo group withdrew from the study prematurely. Adverse events, primarily gastrointestinal, were the main reason for withdrawal in the actively treated group. Intention-totreat analyses showed significant improvements over time in both groups in ESR, pain, and number of swollen joints (P < 0.01). Number of days on sick leave decreased significantly in the sulphasalazine group only (P < 0.01). No significant diVerences between the two groups were present after six months. Among the patients completing the trial according to protocol, persistent complete remission had occurred within two months in five (23%) of the actively treated, but in no placebo treated patients (P = 0.013). Conclusions—Sulphasalazine seemed to improve only the very short term outcome of reactive arthritis. The possible beneficial eVect of the drug should also be weighed against the risk of adverse events. Although these were mainly mild, almost 25% of the patients in the actively treated group gave up treatment for this reason. (Ann Rheum Dis 1997;56:32–36) The traditional treatments in reactive arthritis consist of non-steroidal anti-inflammatory drugs and physiotherapy. Such treatments can only be considered palliative and have not been shown to change the course of the disease. No disease modifying agent is currently available for patients with aggressive disease. The clinical entity of reactive arthritis bears some resemblance to the HLA-B27 related arthropathies, ankylosing spondylitis and psoriatic arthritis (HLA-B27 association, spondylitis, extra-articular manifestations), and also to rheumatoid arthritis (peripheral arthritis), in which a beneficial eVect of sulphasalazine has been shown. 2 In addition, inflammatory lesions have been found in the ileum and colon of patients with reactive arthritis, even in the absence of intestinal symptoms. These lesions resemble those found in the classical inflammatory bowel diseases, where sulphasalazine is an established treatment. Open studies and retrospective analyses have suggested an eVect of the drug in reactive arthritis. 8 9–11 Recently, a double blind placebo controlled trial of sulphasalazine in spondylarthropathies has suggested a marked eVect of the active drug in psoriatic arthritis, but not in the subgroup classified as having reactive arthritis. The present prospective, double blind, placebo controlled study was undertaken in order to evaluate the eVect of sulphasalazine in patients suVering from reactive arthritis. Methods Five centres participated in the study. Patients above the age of 18 years with active reactive arthritis were eligible for the trial. This condition was defined as the presence for at least four weeks of at least one peripheral swollen joint despite non-steroidal anti-inflammatory drug (NSAID) treatment, and providing rheumatoid arthritis, septic arthritis, crystal arthropathies, ankylosing spondylitis, psoriasis, inflammatory bowel diseases, and acute intermittent porphyria had been excluded. Axial involvement, extra-articular manifestations, and history of urethritis, cervicitis, or enteritis were not obligatory. Further exclusion criteria were a history of glucose-6-phosphate dehydrogenase deficiency, known allergy to salicylic acid or sulphonamides, low neutrophil count (<1.5 × 10 litre), low platelet count (<100 × 10 litre), significant impairment of hepatic or renal function, previous sulphasalazine treatment, and oral or intra-articular glucocorticoid treatment within the past four weeks. Pregnant and lactating women and patients planning to conceive within the study period were also excluded. The trial period was six months. Trial medication consisted of sulphasalazine (Salazopyrin EN tablets) and matching placebo and was kindly supplied by Pharmacia AS, Denmark. The dose regimen was one 500 mg tablet twice daily in the first week, two tablets twice daily in the second week, and three journal Annals of the Rheumatic Diseases 1997;56:32–36 32 Department of Rheumatology, Copenhagen Municipal Hospital, Copenhagen and GentofteUniversity Hospital, Hellerup, Denmark C Egsmose Department of Rheumatology, Herlev University Hospital, Herlev, Denmark T M Hansen Department of Rheumatology, King Christian X Rheumatism Hospital, Graasten, Denmark L S Andersen Department of Rheumatology, Odense University Hospital, Denmark J M Beier L Ejstrup Department of Rheumatology, Hjørring Hospital, Denmark N D Peters Department of Rheumatology, University Hospital Maastricht, The Netherlands DM F M van der Heijde Correspondence to: Charlotte Egsmose, Department of Rheumatology B4, Slagelse County Hospital, DK-4200 Slagelse, Denmark. Accepted for publication 4 September 1996 group.bmj.com on June 20, 2017 Published by http://ard.bmj.com/ Downloaded from