POS1041 LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS REFRACTORY TO BIOLOGIC THERAPIES: 2-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 2 STUDY

Abstract

BackgroundUpadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study.1ObjectivesTo evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2.MethodsPts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks; PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104.ResultsA total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56.1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information; however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia).Table 1.Efficacy Endpoints at Week 104EndpointUPA15 (n=211)UPA30 (n=218)Proportion of Pts (%)aNRIAONRIAOACR2055.580.354.681.8ACR5044.562.939.959.4ACR7023.232.221.631.5Minimal Disease Activity (MDA)29.441.333.949.3PASI75b47.769.852.781.1PASI90b37.755.244.367.8PASI100b23.135.435.955.6Resolution of enthesitis by LEIc39.867.837.568.4Resolution of dactylitis by LDId54.597.452.096.9Change from BLeMMRMAOMMRMAOHealth Assessment Questionnaire - Disability Index (HAQ-DI)-0.36-0.39-0.50-0.53Patient’s assessment of pain (numeric rating scale)-2.7-3.0-2.9-3.1Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)f-2.6-3.0-2.6-2.9Ankylosing Spondylitis Disease Activity Score (ASDAS)f-1.4-1.7-1.3-1.5ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; 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.ConclusionIn PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identified in this long-term extension.