Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission on Combination Therapy: A Randomized, Double-Blind Trial.

OBJECTIVE Patients with rheumatoid arthritis (RA) achieving remission on methotrexate plus etanercept therapy (Combo) face ongoing medication burden. Whether those in sustained remission on Combo can maintain remission with monotherapy (mono) after discontinuing either methotrexate or etanercept has not been adequately tested. METHODS Adult RA patients on Combo (N=371) maintaining Simplified Disease Activity Index (SDAI) remission through a 24-week open-label period (N=253) entered a 48-week, double-blind period and were randomized to: (1) methotrexate-mono (N=101); (2) etanercept-mono (N=101); or (3) Combo (N=51). Patients with disease-worsening received Combo rescue therapy at prior dosages. The primary endpoint was the proportion of patients in SDAI remission without disease-worsening at week 48 in the etanercept-mono vs methotrexate-mono arms. Secondary endpoints included time to disease-worsening and proportion of patients recapturing SDAI remission after rescue therapy. RESULTS Baseline characteristics were similar across treatment arms. At week 48, SDAI remission was maintained by significantly more patients on etanercept-mono vs methotrexate-mono (49.5% vs 28.7%; P=0.004) and by more patients on Combo vs methotrexate-mono (52.9% vs 28.7%; P=0.006; secondary endpoint). Time to disease-worsening was shorter with methotrexate-mono compared with etanercept-mono and Combo (P<0.001 for both comparisons). Among patients receiving rescue therapy, 70-80% in each arm recaptured SDAI remission. No new safety signals were reported. CONCLUSIONS Etanercept-mono was superior to methotrexate-mono and similar to Combo in maintaining remission during the double-blind phase. Most patients on rescue therapy recaptured remission. These data inform decision-making around withdrawing therapy to reduce treatment burden in well-controlled RA.