Etanercept vs. Methotrexate: How Do These Drugs Compare in RA Patients in Remission?

Among patients with rheumatoid arthritis (RA) who have achieved remission following combination methotrexate plus etanercept, monotherapy with etanercept was superior to methotrexate, according to a study.

“These data could inform decision‐making when withdrawal of therapy is being considered to reduce treatment burden in patients with well‐controlled RA,” the researchers concluded.

The Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Rheumatoid Arthritis (SEAM‐RA) initially included 371 adults with RA received combination methotrexate plus etanercept therapy. Of these patients, 253 achieved and sustained remission (Simplified Disease Activity Index [SDAI] score ≤3.3) over a 24-week, open-label period and were included in a 48-week, double-blind period, at which time they were randomized to receive either methotrexate monotherapy (n=101), etanercept monotherapy (n=101), or combination methotrexate plus etanercept (n=51). If patients experienced disease-worsening they were given rescue therapy. The main outcome was the proportion of patients who maintained SDAI-defined remission, without their disease worsening, at week 48 between the etanercept versus methotrexate monotherapy groups; secondary outcomes were time to disease-worsening and the proportion of patients who recaptured SDAI-defined remission following rescue therapy.

At 48 weeks, patients in the etanercept monotherapy group were much more likely to have maintained SDAI-defined remission compared to those in the methotrexate monotherapy group (49.5% vs. 28.7%; P=0.004). A much greater proportion of patients receiving combination therapy achieved and sustained SDAI-defined remission compared to those on methotrexate monotherapy (52.9% vs. 28.7%; P=0.006). Patients in the methotrexate monotherapy group had a shorter time to disease-worsening compared to those in both the etanercept monotherapy and combination therapy groups (each P<0.001 versus methotrexate monotherapy). In each group, a high proportion of patients who were given rescue therapy successfully re-achieved SDAI-defined remission.

The study was published in Arthritis & Rheumatology.

“Overall, the results of the SEAM‐RA study provide information on the likelihood of success of discontinuing methotrexate and can inform general decision‐making around RA treatment strategies. These results may be of particular interest to physicians and patients concerned about adverse events, such as nausea and fatigue, and long‐term safety issues associated with methotrexate,” the researchers wrote in their conclusion.