POS0081 LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 2-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY

Abstract

BackgroundIn SELECT-PsA 1, patients (pts) with psoriatic arthritis (PsA) and an inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug showed improvement in the signs and symptoms of PsA with upadacitinib 15 mg (UPA15) or 30 mg (UPA30), an oral Janus kinase (JAK) inhibitor, through week (wk) 56.1ObjectivesTo evaluate the efficacy and safety of UPA and UPA vs adalimumab (ADA) at wk 104 from the ongoing long-term extension of SELECT-PsA 1.MethodsPts received UPA15, UPA30, ADA 40 mg, or placebo (PBO) for 24 wks, at which point, PBO pts switched to UPA15 or UPA30. Efficacy endpoints were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures and AO (continuous endpoints), with nominal P-values shown, for continuous UPA and ADA treatment groups. Treatment-emergent adverse events were summarized for pts who received ≥1 dose of study drug using a visit-based cut-off at wk 104.Results1704 pts received ≥1 dose of study drug. At wk 104, 25.4% of patients had discontinued study drug. The proportions of pts who achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of enthesitis or dactylitis showed consistent responses, or further improvements, from wk 561 to wk 104 (Table 1). ACR20/50/70 and MDA responses, as well as mean change from baseline (BL) in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS, were greater with UPA vs ADA. Mean change from BL in modified total Sharp/van der Heijde Score (mTSS) was generally similar across groups and comparable to wk 56.1 The safety profile of UPA was generally comparable to ADA (Figure 1) and consistent with wk 561 data. Rates of serious infection, herpes zoster, lymphopenia, and elevated CPK remained numerically higher with UPA30 vs UPA15; rates in both UPA groups were higher vs ADA. Rates of malignancies, MACE, or VTE were similar across groups, and consistent with wk 561 data. Two deaths were reported with UPA15, 1 with UPA30, and 1 with ADA.Table 1.Efficacy Endpoints at Week 104EndpointUPA15(n=429)UPA30(n=423)ADA(n=429)Proportion of Pts (%)aNRIAONRIAONRIAOACR2069.087.969.587.963.485.1ACR5053.667.459.3*74.147.162.3ACR7038.0*47.443.5*54.429.439.1Minimal Disease Activity (MDA)42.054.845.9*56.837.850.3PASI75b57.973.462.478.658.876.5PASI90b46.759.053.366.548.863.3PASI100b34.143.442.451.434.144.0Resolution of enthesitis by LEIc53.375.552.272.049.173.9Resolution of dactylitis by LDId69.994.571.796.272.495.2Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire - Disability Index (HAQ-DI)-0.55*-0.57-0.55*-0.59-0.45-0.47Patient’s assessment of pain (numeric rating scale)-3.3-3.5-3.4*-3.6-3.0-3.2Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)f-3.0-3.2-3.3-3.6-2.7-2.6Ankylosing Spondylitis Disease Activity Score (ASDAS)f-1.6-1.8-1.9*-2.1-1.5-1.6Modified total Sharp/van der Heijde Score (mTSS)0.030.010.010.000.110.11ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; ADA, adalimumab; AO, as observed; BL, baseline; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pts, patients; UPA, upadacitinib.aData shown as NRI and AO for binary endpoints.bFor pts with psoriasis affecting ≥3% of body surface area at BL.cFor pts with LEI >0 at BL; resolution LEI=0.dFor pts with LDI >0 at BL; resolution LDI=0.eData shown as MMRM (LS mean) and AO (mean) for continuous endpoints.fFor pts with psoriatic spondylitis at BL.Nominal *P<0.05, UPA15 or UPA30 vs ADA for NRI and MMRM; AO descriptive only.ConclusionIn PsA pts, efficacy responses were similar or greater with UPA15 or UPA30 vs ADA at wk 104, and inhibition of radiographic progression was maintained. No new safety signals were identified with long-term exposure to UPA up to 2 years.