RANDOMIZED COMPARISON OF COMBINED STEP-DOWN PREDNISOLONE, METHOTREXATE AND SULFASALAZINE WITH SULFASALAZINE ALONE IN EARLY RHEUMATOID-ARTHRITIS

Background The value of intensive combination therapy in early rheumat oid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day) , methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, t apered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. Met hods 155 patients with early rheumatoid arthritis (median duration 4 m onths) were randomly assigned combined treatment (76) or sulphasalazin e alone (79). Prednisolone and methotrexate were tapered and stopped a fter 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of live disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes witho ut knowledge of treatment allocation. Findings At week 28, the mean po oled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group an d 0.8 (0.6-1.0) in the sulphasalazine group (p<0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after predn isolone was stopped, and there were no further changes after methotrex ate was stopped. At 28 weeks, the radiographic damage score had increa sed by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p<0.0001). The increases at week 5 6 (2 [0-43] vs 6 [0-54], p=0.004), and at week 80 (4 [0-80] vs 12 [0-7 2], p=0.01) were also significant. Further analysis suggests that comb ined therapy immediately suppressed damage progression, whereas sulpha salazine did so less effectively and with a lag of 6 to 12 months. The re were fewer withdrawals in the combined therapy than the sulphasalaz ine group (6 [8%] vs 23 [29%]), and they occurred later. Interpretatio n This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.