Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase 3 Trial.

Document Type


Publication Date


Publication Title

Arthritis Rheumatol


OBJECTIVE: To examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept in patients with psoriatic arthritis (PsA).

METHODS: In this double-blind study, 851 PsA patients were randomized to: oral methotrexate 20mg plus placebo weekly (N=284), etanercept 50mg plus placebo weekly (N=284), or etanercept 50mg plus oral methotrexate 20mg weekly (combination therapy; N=283). American College of Rheumatology (ACR)20 response and Minimal Disease Activity (MDA) response at week 24 were the primary and key secondary endpoints, respectively. Other measures of inflammatory arthritis, radiographic progression, and non-articular disease manifestations were also assessed.

RESULTS: Mean (standard deviation [SD]) age was 48.4 (13.1) years; mean PsA duration was 3.2 years (SD: 6.3; median: 0.6). ACR20 and MDA responses at week 24 were significantly greater for etanercept monotherapy vs methotrexate monotherapy (ACR20: 60.9% vs 50.7% [P=0.029]; MDA: 35.9% vs 22.9% [P=0.005]) and for combination therapy vs methotrexate monotherapy (ACR20: 65.0% vs 50.7% [P=0.005]; MDA: 35.7% vs 22.9% [P=0.005]). Other secondary outcomes (ACR50, ACR70, Very Low Disease Activity score, and Psoriatic Arthritis Disease Activity Score) were consistent with these results. The etanercept-containing arms showed less radiographic progression compared with methotrexate monotherapy at week 48. Combination therapy and etanercept monotherapy had similar results except for some skin endpoints. No new safety signals were seen.

CONCLUSION: Etanercept monotherapy and combination therapy showed greater efficacy than methotrexate monotherapy in ACR and MDA responses and radiographic progression. Overall, combining methotrexate and etanercept did not improve etanercept efficacy. This article is protected by copyright. All rights reserved.

Clinical Institute

Orthopedics & Sports Medicine