AB0260 LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS FROM CHINA, BRAZIL, AND SOUTH KOREA WITH RHEUMATOID ARTHRITIS AND AN INADEQUATE RESPONSE TO CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS: RESULTS AT 64 WEEKS

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Background:Upadacitinib (UPA), an oral Janus kinase inhibitor, in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), showed significant improvements in clinical and functional measures compared with placebo (PBO) up to 12 weeks (wks), in patients (pts) from China, Brazil, and South Korea with rheumatoid arthritis (RA) and prior inadequate response to csDMARDs (csDMARD-IR).1Objectives:To assess the efficacy and safety of UPA up to 64 wks (long-term extension; LTE) in csDMARD-IR pts with RA from China, Brazil, and South Korea.Methods:Pts were randomized to 12 wks of blinded treatment with UPA 15 mg once daily (QD) or PBO, in combination with csDMARDs. From Wk 12 onward, pts could continue to receive open-label UPA 15 mg QD. Efficacy endpoints were analyzed by original randomized treatment group sequences over 64 wks and included American College of Rheumatology (ACR) responses, and key remission and low disease activity measures. Non-responder imputation was used to handle missing data for binary endpoints. Treatment-emergent adverse events (TEAEs) per 100 patient-years (PY) were summarized for pts receiving ≥1 dose of UPA from baseline through to Wk 64.Results:Of 338 randomized pts who received ≥1 dose of study drug, 310 (91.7%) entered the LTE and 275 (81.4%) completed 64 wks of treatment. Among those initially randomized to UPA, the proportion of pts achieving 20%/50%/70% improvement in ACR criteria, and key remission and low disease activity measures increased over 64 wks of treatment (Figure 1). Improvements from baseline in the Health Assessment Questionnaire-Disability Index and pts’ assessment of pain were observed over 64 wks of UPA treatment (data not shown). By Wk 64, efficacy results for pts who switched from PBO to UPA at Wk 12 followed a similar trajectory to those originally randomized to UPA.The observed rate of serious infections was 8.1 events/100 PY. Herpes zoster events were mostly non-serious, involving only 1 or 2 dermatomes. Most cases of hepatic disorders were Grade 1 or 2 hepatic transaminase elevations. There was 1 case of venous thromboembolic event (VTE; concurrent pulmonary embolism and deep vein thrombosis [DVT] in a patient with a history of DVT) and 3 cases of malignancy. Adjudicated major adverse cardiovascular events (Table 1) occurred in 2 pts (1 with non-fatal myocardial infarction and 1 with non-fatal stroke) who had underlying risk factors for cardiovascular disease. There were no deaths, active tuberculosis, or renal dysfunction.Conclusion:UPA 15 mg was effective in treating the signs and symptoms of RA and in improving physical function over 64 wks with no new safety signals1 in csDMARD-IR pts with RA from China, Brazil, and South Korea.