POS0655 LONG-TERM SAFETY AND EFFICACY OF UPADACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: 3-YEAR RESULTS FROM THE SELECT-EARLY STUDY

Abstract

Background:Upadacitinib (UPA), an oral Janus kinase inhibitor, demonstrated significant improvements in signs, symptoms, and structural inhibition as monotherapy (mono) vs methotrexate (MTX) in MTX-naïve patients (pts) with rheumatoid arthritis (RA) through 48 weeks (wks).1Objectives:To report the efficacy and safety of UPA vs MTX mono up to 156 wks in pts with RA from the ongoing long-term extension (LTE) of the SELECT-EARLY trial.Methods:During the 48-wk double-blind study period, pts were randomized to UPA 15 or 30 mg once daily (QD) or MTX (titrated to 20 mg/wk by Wk 8). At Wk 26, pts who did not achieve Clinical Disease Activity Index (CDAI) remission (≤2.8) and had <20% improvement from baseline in tender or swollen joint count received blinded rescue therapy (addition of MTX for UPA groups and UPA 15 or 30 mg for MTX group). In the LTE, pts received open-label treatment once the last pt reached Wk 48. Efficacy assessments up to Wk 156 were summarized by randomized group and included American College of Rheumatology (ACR) responses, remission and low disease activity (LDA) measures, and change in modified Total Sharp Score (mTSS; up to 96 wks). Treatment-emergent adverse events (AEs) per 100 pt-years (PY) for pts on continuous mono were summarized through 156 wks. Non-responder imputation was used for binary endpoints for missing data and when pts received rescue therapy or prematurely discontinued the study drug.Results:Of 945 pts randomized and treated, 775 entered the LTE on study drug (including 57 rescued pts; MTX, 33; UPA 15 mg, 17; UPA 30 mg, 7). Overall, 161 (21%) pts discontinued during the LTE. At Wk 156, higher proportions of pts randomized to UPA achieved a 20/50/70% improvement in ACR response (ACR20/50/70), LDA, and remission vs MTX (Figure 1). Change from baseline in mTSS at Wk 96 favored UPA vs MTX (data not shown). Most AEs were numerically more frequent with UPA 30 mg. The overall rate of serious infection was numerically higher with UPA vs MTX (Table 1). Herpes zoster (HZ), neutropenia, non-melanoma skin cancer (NMSC), and creatine phosphokinase (CPK) elevation were more frequent with UPA vs MTX. Two active tuberculosis (TB) events were reported in each UPA arm; 3 adjudicated gastrointestinal (GI) perforation events were observed in the UPA 30 mg arm. Adjudicated major adverse cardiovascular events (MACEs) or venous thromboembolic events (VTEs) were comparable across treatment arms.Conclusion:UPA monotherapy showed sustained clinically meaningful responses including remission vs MTX through Wk 156 but higher rates of several AEs, including HZ, neutropenia, and CPK elevations; no new safety risks were observed compared with previous results.1,2