OP0144 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 1-YEAR RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY WITH OPEN-LABEL EXTENSION

Abstract

Background:Upadacitinib (UPA) was efficacious and well tolerated vs placebo (PBO) during the first 14 weeks (wks) of the phase 2/3 SELECT-AXIS 1 study in patients (pts) with active ankylosing spondylitis (AS) who had an inadequate response to NSAIDs.1Objectives:To report efficacy and safety of UPA through 1 year in the SELECT-AXIS 1 study.Methods:In SELECT-AXIS 1 (NCT03178487) pts were randomized 1:1 to UPA 15 mg once daily (QD) or PBO; at wk 14, pts continued in the 90-wk open-label extension and received UPA 15 mg QD; reported here are data up to wk 64. The study enrolled pts (≥18 y) with active AS (defined as BASDAI ≥4 and pt assessment of back pain ≥4 [numeric rating scale, 0–10] at screening and baseline [BL]) who had inadequate response to ≥2 NSAIDs or intolerance to or contraindication for NSAIDs and were biologic DMARD naive. Efficacy assessments included percentage of pts with Assessment of SpondyloArthritis international Society (ASAS) 20/40 response, ASAS partial remission, BASDAI50, AS Disease Activity Score (ASDAS) and change from BL in ASDAS and BASFI. Data are reported as observed and by using non-responder imputation (NRI). Treatment-emergent adverse events (TEAEs) were reported as events per 100 patient-years (PY) up to January 31, 2020.Results:Of 187 pts, 178 pts (each n=89 for UPA and PBO arms) completed wk 14 on study drug and entered the open-label extension; 160 pts completed wk 64. Efficacy was maintained or continued to improve throughout the study in the continuous UPA group: 85% (95% CI, 77%–93%) of pts achieved ASAS40 at wk 64 in the as-observed analysis and 72% (63%–81%) in the NRI analysis (Figure). Pts who switched from PBO to UPA at wk 14 showed similar speed of onset and magnitude of response vs pts initially randomized to UPA: 81% (95% CI, 72%–89%) in the as-observed analysis and 70% (61%–80%) in the NRI analysis achieved ASAS40 at wk 64 (Figure). Similar results were observed for other efficacy endpoints (Figure). Among all 182 pts receiving UPA, 618 AEs were reported. AEs leading to discontinuation and serious AEs were low (Table). No serious infections, active tuberculosis, venous thromboembolic events, gastrointestinal perforation, major adverse cardiovascular events, renal dysfunction, or deaths were reported.Table 1.TEAEs per 100 PYsEvents/(E/100 PY)UPA 15 mg QDN=182 (237.6 PY)Any AE618 (260.1)Serious AE14 (5.9)AE leading to discontinuation15 (6.3)Infections205 (86.3) Opportunistic infection*2 (0.8) Herpes zoster†5 (2.1)Creatine phosphokinase elevation‡28 (11.8)Hepatic disorder§24 (10.1)Neutropenia||7 (2.9)Anemia||3 (1.3)Lymphopenia||2 (0.8)Malignancy¶1 (0.4)Death0AE, adverse event; PY, patient-year; QD, once daily; TEAE, treatment-emergent AE; UPA, upadacitinib.*Two non-serious events of esophageal candidiasis in the same patient.†Five events in 4 patients; all non-serious and limited to 1 dermatome.‡All events were non-serious and none led to study drug discontinuation; majority were asymptomatic.§Majority based on asymptomatic alanine aminotransferase/aspartate aminotransferase elevations; all were non-serious and none led to study drug discontinuation.||All events were non-serious and none led to study drug discontinuation.¶Squamous cell carcinoma of tongue in 61-year-old male former smoker; no reasonable possibility to be study drug related per investigator.Conclusion:UPA 15 mg QD showed sustained and consistent efficacy over 1 year. Pts who switched from placebo to UPA at wk 14 showed a similar efficacy response compared with pts who received continuous UPA. No new safety findings were observed compared with safety data from the UPA clinical development program in other indications.2