Outcomes Switching to Monotherapy: SEAM-RA Trial Save

Combination therapy with biologic and conventional DMARDs can be highly effective at inducing remission in patients with rheumatoid arthritis. Once controlled under therapy, patients are often very interested in stopping combination drug therapy due to concerns related to medication burdens, side effect profiles, or safety. 

Dr. Jeffrey Curtis from University of Alabama at Birmingham talked at today’s plenary session about the results of the SEAM-RA, Study of Etanercept And Methotrexate in RA, trial (abstract #0939), which evaluated discontinuing combination therapy in stable rheumatoid arthritis patients in disease remission. In a 48-week, double-blind study, patients were randomized to three groups: (1) withdrawal of etanercept (methotrexate monotherapy), (2) withdrawal of methotrexate (etanercept monotherapy) or (3) continuation of combination therapy.  

Results showed that patients who decreased to methotrexate monotherapy were more likely to have disease-worsening than patients on etanercept monotherapy or patients who remained on combination therapy. The group on etanercept monotherapy did about as well as the patients who remained on combination therapy. For patients that did develop worsening disease, combination rescue therapy was able to recapture disease remission in the majority of patients. No safety signals were noted in the study. 

This study shows that patients on combination therapy who are interested in switching to monotherapy are less likely to flare with withdrawal of the methotrexate, than with withdrawal of TNF-inhibitor. Decreasing to biologic-only therapy is a reasonable option without an increased risk of disease flare. 

Though useful, however, many questions remain unanswered by this study to inform clinical judgement for patients in remission on combination therapy. Methotrexate improved not only disease control, but also is effective in the prevention of anti-drug-antibodies. The patients in the SEAM-RA trial did not have disease worsening after the withdrawal of methotrexate in the first 48 months, but longer follow-up studies after drug withdrawal would likely show that methotrexate can extend the longevity of biologic usage. 

In patients on combination therapy in remission who are interested in decreasing their medication burden, this is a well-designed study to assure your patients that they are likely to remain under good control on biologic therapy and would respond well to rescue combination therapy, if needed. If the combination therapy is well-tolerated, however, I would still recommend continuing the combination therapy as this study does not address the long-term benefits of anti-drug antibody formation and biologic longevity.