OP0050 ADALIMUMAB INTRODUCTION VERSUS METHOTREXATE DOSE ESCALATION IN PATIENTS WITH INADEQUATELY CONTROLLED PSORIATIC ARTHRITIS: RESULTS FROM RANDOMIZED PHASE 4 CONTROL STUDY

Abstract

Background: Methotrexate (MTX) is often used as first-line therapy for patients (pts) with psoriatic arthritis (PsA) despite limited efficacy and data on appropriate dosage. Minimal Disease Activity (MDA) is suggested as an optimal treat-to-target outcome. Biologic disease-modifying antirheumatic drugs (bDMARDs) have demonstrated improved outcomes (including MDA rates) over MTX. However, more data are needed to define the optimal timing of bDMARD initiation and characterize efficacy of MTX dose escalation, to achieve optimal outcomes. Objectives: To compare achievement of MDA between adding adalimumab (ADA) vs escalating MTX dose in PsA pts with inadequate disease control after initial MTX therapy. Methods: The open-label, 2-part CONTROL study enrolled bDMARD-naive adult pts with active PsA (not in MDA at screening and ≥3 tender and ≥3 swollen joints) despite MTX 15 mg every wk (ew) for ≥4 wks. Pts were randomized to ADA 40 mg every other wk + MTX 15 mg (ADA+MTX) or escalated MTX to 20-25 mg ew or highest tolerable dose during 16-wk part 1 (Fig 1). The primary endpoint was achievement of MDA, defined as fulfilling ≥5 of the 7 criteria: tender joint count 68 (TJC68) ≤1, swollen joint count 66 (SJC66) ≤1, Psoriasis Area Severity Index (PASI) ≤1 or body surface area (BSA) ≤3%, pt's pain (visual analogue scale [VAS] 0-100) ≤15, Pt's Global Assessment of disease activity (PtGA) VAS ≤20, Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5 and tender entheseal points (0-8) ≤1. Key secondary efficacy endpoints were achievement of ACR20 and PASI75 and change from baseline in HAQ-DI and Leeds Enthesitis Index (LEI) at wk 16. Results: Overall, 246 pts were randomized; 245 received treatment (ADA+MTX, n=123; escalated MTX, n=122); 117 (95%) pts and 110 (90%) pts, respectively, completed part 1. Baseline characteristics were similar between groups (Table). During part 1, the average dose of MTX was 21.8 mg/wk (55% on oral MTX) in the escalated MTX group. Significantly higher proportion of pts in ADA+MTX (42%) vs escalated MTX (13%) group achieved MDA at wk 16 (non-responder imputation [NRI]; difference [95% CI] 28% [18%-39%]; P<0.001; Fig 2). Observed case analysis confirmed the NRI analysis. Lower MDA rates at wk 16 were observed in the escalated MTX arm regardless of prior MTX duration (Fig 2). Significant improvements in key secondary endpoints were also observed with ADA+MTX vs escalated MTX (all P<0.05; Fig 2). In part 1, the proportion of patients with adverse events was similar between groups (ADA+MTX, 62% vs escalated MTX, 57%); no opportunistic infections, tuberculosis, malignancies, or deaths were reported during part 1. Conclusion: A significantly higher proportion of pts achieved MDA at wk 16 after introducing ADA compared with escalating MTX dose; higher rates were observed regardless of prior MTX duration. Significantly higher responses in musculoskeletal, skin, and quality of life measures were observed with ADA+MTX vs escalated MTX. No new safety signals with ADA were identified in this pt population. (Figure Presented).