Key result
Initial combination therapy cuts joint damage progression ~50% vs monotherapy or step-up therapy.
Why the study?
Does initial combination therapy improve functional ability and reduce joint damage in patients with early active rheumatoid arthritis compared to sequential monotherapy or step-up combination therapy?
RCT (n=508)
Open-label with blinded assessors
Randomized
Yes
Does initial combination therapy improve functional ability and reduce joint damage in patients with early active rheumatoid arthritis compared to sequential monotherapy or step-up combination therapy?
p-value: p=0.004
In early rheumatoid arthritis, initial combination therapy provides earlier clinical improvement and better suppression of joint damage progression compared to monotherapy, though functional outcomes equalize by 2 years.
Supports initial combination therapy to limit structural damage in early RA; strengthens evidence for aggressive DMARD strategies.
Background: In patients with early rheumatoid arthritis, initial combination therapies provide earlier clinical improvement and less progression of joint damage after 1 year compared with initial monotherapies (as demonstrated in the BeSt study). Objective: To evaluate whether the initial clinical and radiographic efficacy of combination therapies could be maintained during the second year of follow-up in patients with early rheumatoid arthritis. Design: Randomized, controlled clinical trial with blinded assessors. Setting: 18 peripheral and 2 university medical centers in the Netherlands. Patients: 508 patients with early active rheumatoid arthritis. Intervention: Sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), or initial combination therapy with infliximab (group 4). Trimonthly treatment adjustments were made to achieve low disease activity. Measurements: Primary end points were functional ability (Health Assessment Questionnaire) and Sharp–van der Heijde score for radiographic joint damage. Results: Groups 3 and 4 had more rapid clinical improvement during the first year; all groups improved further to a mean functional ability score of 0.6 (overall, P = 0.257) and 42% were in remission (overall, P = 0.690) during the second year. Progression of joint damage remained better suppressed in groups 3 and 4 (median scores of 2.0, 2.0, 1.0, and 1.0 in groups 1, 2, 3, and 4, respectively [P = 0.004]). After 2 years, 33%, 31%, 36%, and 53% of patients in groups 1 through 4, respectively, were receiving single-drug therapy for initial treatment. There were no significant differences in toxicity. Limitations: Patients and physicians were aware of the allocated group, and the assessors were blinded. Conclusions: Currently available antirheumatic drugs can be highly effective in patients with early rheumatoid arthritis in a setting of tight disease control. Initial combination therapies seem to provide earlier clinical improvement and less progression of joint damage, but all treatment strategies eventually showed similar clinical improvements. In addition, combination therapy can be withdrawn successfully and less treatment adjustments are needed than with initial monotherapies.
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Goekoop-Ruiterman et al. (2007) conducted an RCT in early active rheumatoid arthritis (n=508). Initial combination therapy (with tapered high-dose prednisone or infliximab) vs. Sequential monotherapy or step-up combination therapy was evaluated on Functional ability (Health Assessment Questionnaire) and Sharp-van der Heijde score for radiographic joint damage (p=0.004). Initial combination therapies better suppressed progression of joint damage compared to monotherapy or step-up therapy (median scores 1.0 vs 2.0, P=0.004), with similar functional improvements.
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