Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis.
Boers, Maarten; Verhoeven, Arco C; Markusse, Harry M; van de Laar, Mart A F J; Westhovens, Rene; van Denderen, J Christiaan; van Zeben, Derkjen; Dijkmans, Ben A C; Peeters, Andre J; Jacobs, Piet; van den Brink, Hans R; Schouten, Hubert J A; van der Heijde, Desiree M F M; Boonen, Annelies; van der Linden, Sjef
[Article]
Lancet.
350(9074):309-318, August 2, 1997.
(Format: HTML)
Summary: Background The value of intensive combination therapy in early rheumatoid arthritis is unproven.In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7[center dot]5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7[center dot]5 mg/day) with sulphasalazine alone.
Methods 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79).Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation.
Findings At week 28, the mean pooled index was 1[center dot]4 (95% Cl 1[center dot]2-1[center dot]6) in the combined treatment group and 0[center dot]8 (0[center dot]6-1[center dot]0) in the sulphasalazine group (p<0[center dot]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 prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p<0[center dot]0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p=0[center dot]004), and at week 80 (4 [0-80] vs 12 [0-72], p=0[center dot]01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later.
Interpretation 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.
Lancet 1997; 350: 309-18
Copyright. (C) The Lancet Ltd, 1997.
