Methotrexate-Refractory Rheumatoid Arthritis Patients See Better Results with Combo Drug Treatment, According to Analysis

Methotrexate-Refractory Rheumatoid Arthritis Patients See Better Results with Combo Drug Treatment, According to Analysis

Korean researchers compared the efficacy of a number of biological agents in rheumatoid arthritis (RA) patients refractory to methotrexate (MTX), and found that certolizumab and golimumab, two monoclonal antibodies that target tumor necrosis factor alpha (TNF-α), combined with MTX, appeared to be most effective.

The findings have been reported in the study “Comparative efficacy of biological agents in methotrexate-refractory rheumatoid arthritis patients: a Bayesian mixed treatment comparison,” recently published in The Korean Journal of Internal Medicine.

Disease-modifying drugs (DMDs) such as MTX, sulfasalazine, hydroxychloroquine, and leflunomide, have been the standard of care for patients with RA. Nonetheless, patients who fail to respond or are intolerant to DMDs have demonstrated significant improvements when treated with biological agents, such as TNF antagonists.

Randomized clinical trials have compared the efficacy of such agents, compared to placebo, in DMD-refractory patients. Therefore, the researchers performed a mixed treatment comparison that allowed them to make indirect comparisons between studies to find the most effective treatment, including both DMDs and biological agents, in MTX-refractory RA patients.

For their analysis, the investigators selected published studies that included at least one of the four DMDs (hydroxychloroquine, sulfasalazine, MTX, leflunomide) or one of the five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, infliximab, and certolizumab).

Among the 7,938 identified studies, only 16 were selected for analysis. A total of 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively.

Among the nine studies included in the HAQ analysis, the treatment that demonstrated the highest efficacy in improving HAQ score was the combination of certolizumab with MTX, followed by the combinations of golimumab with MTX and adalimumab with MTX.

In the four studies that included the DAS28-ESR < 2.6 (remission) analysis, the most effective treatment was golimumab with MTX, where the odds of patients entering remission were 24.5 times higher than in the MTX group.

Among the 11 studies that included ACR response analysis, the most effective treatment was certolizumab with MTX. Patients receiving this treatment showed 10.4 increased odds of having at least a 70 percent improvement in the number of tender and swollen joints.

“In conclusion, based on an MTC analysis using data from published RCTs, the combinations of certolizumab or golimumab with MTX are most effective in improving HAQ, DAS28-ESR < 2.6, and ACR 70 response in MTX-refractory RA patients.” the authors concluded in their study.

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