SAT0160 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS FROM CHINA, BRAZIL, AND SOUTH KOREA WITH RHEUMATOID ARTHRITIS WHO HAVE HAD INADEQUATE RESPONSE TO CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
Authors: X. Zeng, D. Zhao, S. Radominski, M. Keiserman, C. K. Lee, S. Meerwein, J. Enejosa, Y. Sui, M. E. Mohamed, W. Park
Journal: Annals of the Rheumatic Diseases (2020)

Background: Upadacitinib (UPA), an oral, selective JAK-1 inhibitor was effective in global ph 3 trials in rheumatoid arthritis (RA) patients with inadequate response (IR)/intolerance to csDMARDs and bDMARDs. Objectives: This Phase 3, randomized, double-blind, placebo (PBO)-controlled study assessed the efficacy and safety of UPA in combination with csDMARDs in csDMARD-IR patients with RA from China, Brazil, and South Korea. Methods: Patients were randomized 1:1 to receive UPA 15 mg once daily (QD) or PBO in combination with csDMARDs. The primary endpoint was ACR20 response at Week 12, using non-responder imputation. Results: 338 patients were randomized, and 310 (91.7%) completed Week 12. At Week 12, statistically significantly more patients receiving UPA vs PBO achieved the primary endpoint of ACR20 (71.6% vs 31.4%, p&lt;0.001). UPA also demonstrated statistically significant improvements in all ranked secondary endpoints vs PBO at Week 12 (Table 1), including mean change in DAS28(CRP), HAQ-DI, and SF-36 PCS, and patients achieving DAS28(CRP) ≤3.2, DAS28(CRP) &lt;2.6, and CDAI ≤10. Greater responses were also seen with UPA vs PBO for other key secondary endpoints including ACR50 and ACR70. Onset of UPA action was rapid with more patients on UPA achieving ACR20 by Week 1 (25.4% vs 5.9%, p&lt;0.001). The frequency of AEs (61.5% vs 49.1%) and serious AEs (7.1% vs 3.0%) was higher with UPA vs PBO. The frequency of AEs of special interest was generally similar between UPA and PBO, with the exception of herpes zoster (1.8% vs 0.6%), hepatic disorders (9.5% vs 7.1%), neutropenia (3.0% vs 0%), and elevated creatine phosphokinase (1.8% vs 0.6%), which were higher with UPA. One case of breast cancer (on Day 1 of study) and one VTE (pulmonary embolism and deep vein thrombosis in a patient with history of deep vein thrombosis) were reported with UPA treatment. Table 1. Efficacy endpoints at Week 12 Endpoint a UPA 15 mg QD (n=169 ) PBO (n=169 ) Primary endpoint ACR20, % 71.6*** 31.4 Secondary endpoints Δ DAS28(CRP) -2.56*** -0.95 Δ HAQ-DI -0.62*** -0.18 Δ SF-36 PCS 8.93 c *** 3.36 d DAS28(CRP) ≤3.2, % 46.2*** 13.6 DAS28(CRP) &lt;2.6, % 29.6*** 5.3 CDAI ≤10, % 35.5*** 11.2 ACR50, % b 40.8*** 8.3 ACR70, % b 21.3*** 3.6 ACR20 at Week 1, % b 25.4*** 5.9 ***p&lt;0.001 vs PBO a NRI for binary endpoints; ANCOVA with multiple imputation for DAS28(CRP) and HAQ-DI; mixed model repeated measures for other continuous endpoints b Unranked secondary endpoint. c n=143. d n=149 Conclusion: Efficacy of UPA was demonstrated in this csDMARD-IR population from China, Brazil, and South Korea. The safety of UPA was comparable with the global Phase 3 program. Disclosure of Interests: : Xiaofeng Zeng Consultant of: MSD Pharmaceuticals, Dongbao Zhao: None declared, Sebastiao Radominski: None declared, MAURO KEISERMAN Speakers bureau: Pfizer, Abbott, Actelion, AstraZeneca, Amgen, Roche, Bristol Myers Squibb, and Janssen and has received clinical trial honoraria from Pfizer, Amgen, AstraZeneca, Anthera Pharmaceuticals, Bristol-Myers Squibb, Biogen Idec Inc, Celltrion Inc., Eli Lilly, Human Genome Sciences, Novartis, Roche, Sanofi, UCB Inc., Chang-Keun Lee: None declared, Sebastian Meerwein Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yunxia Sui Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Mohamed-Eslam Mohamed Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Won Park: None declared