Reduced/withdrawn dose of etanercept-methotrexate therapy of early rheumatoid arthritis has a favorable impact on patient-reported outcomes compared with MTX alone or placebo: The prize study

Background Open-label etanercept (ETN) + methotrexate (MTX) therapy in early rheumatoid arthritis (RA) yielded high clinical remission and improvements in patient-reported outcomes (PROs) in PRIZE Phase 1 (moderate-severe RA ≤1yr; MTX and biologic naïve pts).1 PRIZE (121-wks, 3-phases) evaluates ETN/MTX efficacy/efficacy maintenance and PROs with reduced/withdrawn therapy in Phase 2. Objectives To assess PROs in PRIZE Phase 2, a 39-wk, 3-arm, double-blind comparison of therapy reduction after a 52 wk induction of 50 mg QW ETN/MTX (Phase 1). Methods Pts achieving DAS28 remission (≤3.2 at wk 39, <2.6 at wk 52) in Phase 1 (n=193) were randomized 1:1:1 for 25 mg ETN + MTX: MTX+PBO injection: PBO capsules + PBO injection. PROs assessed included the Health Assessment Questionnaire disability index (HAQ-DI); EuroQol-5 Dimensions utility score (EQ-5D); Short Form Health Survey P/MCS Physical/Mental Component Summary; Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue); Work Productivity and Activity Impairment Questionnaire (WPAI:RA) and Work Instability Scale for Rheumatoid Arthritis (RA-WIS). Results With dose reductions/withdrawals in Phase 2, the maintenance of effect in PROs was greater at LOCF in the ETN25 + MTX treatment group compared with the PBO group for: HAQ-DI, EQ-5D utility, EQ-5D VAS, SF-36 MCS/PCS, FACIT, and WPAI sub-scales. Additionally, at Phase 2 LOCF clinically meaningful improvements, relative to start of trial, in HAQ-DI (≥0.22); EQ-5D utility (≥0.05) and VAS >82; SF-36 P/MCS (>5) and statistically significantly greater proportions of pts with low and low/medium risk RA-WIS score (≤9 and ≤17) were observed in favor of ETN + MTX vs PBO; the relative benefits of MTX vs PBO were less. Conclusions ETN25 + MTX had a favorable impact on PROs compared to PBO, with greater maintenance of therapeutic effect from baseline to LOCF. (Figure Presented).