AB0392 EFFICACY AND SAFETY OF UPADACITINIB IN A CHINESE SUBGROUP OF PATIENTS WITH RHEUMATOID ARTHRITIS AND INADEQUATE RESPONSE TO CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS

Abstract

BackgroundUpadacitinib (UPA) was effective in global Phase 3 trials in rheumatoid arthritis (RA) patients (pts) with inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).ObjectivesTo assess the efficacy and safety of UPA in csDMARD-IR pts with RA in Chinese subgroup from a Phase 3, randomized, double-blind, placebo (PBO)-controlled study (NCT02955212) 1.MethodsPts were randomized to 12 weeks of blinded treatment with UPA 15 mg once daily (QD) or PBO, in combination with csDMARDs. Primary and secondary endpoints were analyzed in a Chinese subgroup, including American College of Rheumatology criteria (ACR) responses, remission and low disease activity measures. Safety was analyzed for pts who received ≥1 dose of study drug.Results228 Chinese pts (67.5% of overall trial population) were randomized and took at least one dose of study drug. Baseline characteristics were generally balanced between UPA and PBO. 46% and 35.1% used methotrexate (MTX) alone as concomitant csDMARD in UPA and PBO group, respectively. 38.9% in UPA and 43.0% in PBO group used concomitant csDMARDs other than MTX and 15.0% and 21.9% respectively used a combination. At week 12, more Chinese pts receiving UPA achieved the primary endpoint of ACR20 compared with PBO (71.9% vs 31.6%, nominal p<0.001). UPA also showed greater improvements in all secondary endpoints vs PBO at Week 12 (Table 1), including ACR50 and ACR70, mean change in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), Short-Form 36-item Health Survey-Physical Component Summary (SF-36 PCS), as well as proportion of pts achieving low disease activity based on DAS28-CRP ≤3.2 and Clinical Disease Activity Index (CDAI) ≤10, and clinical remission based on DAS28-CRP <2.6. Onset of response was rapid with more pts receiving UPA achieving ACR20 by Week 1 versus PBO (25.4% vs 5.3%, nominal p<0.001). Through Week 12 treatment-emergent adverse events (TEAEs) occurred in 57.9% of pts on UPA and 49.1% on PBO. The rate of pts with serious AEs (SAEs) was numerically higher with UPA than with PBO (6.1% vs 4.4%). TEAEs reported in ≥ 3% of subjects and with a higher rate on UPA vs. PBO were: upper respiratory tract infection, alanine aminotransferase increased, aspartate aminotransferase increased, hypertension, diarrhea, and leukopenia. Overall safety was consistent with the trial population1 and similar with the reported safety profile of the global clinical program2.Table 1.Summary of Efficacy Endpoint Results at Week 12 in Chinese SubgroupEndpoint aUPA 15mg (N=114)PBO (N=114)Primary endpointACR20, %71.9***31.6Secondary endpointsΔ DAS28-CRP-2.42***-0.75Δ HAQ-DI-0.55***-0.11Δ SF-36 PCS7.63 b***2.94 cDAS28-CRP ≤3.2, %46.5***9.6DAS28-CRP <2.6, %28.1***1.8CDAI ≤10, %33.3***7.0ACR50, %39.5***7.0ACR70, %16.7***2.6ACR20 at Week 1, %25.4***5.3***Nominal p<0.001 vs PBOaNon-responder imputation for binary endpoints; ANCOVA with multiple imputation for DAS28(CRP) and HAQ-DI; mixed model repeated measures for other continuous endpoints. Δ: mean change from baselinebN=106cN=104ConclusionUPA demonstrated clinical and functional improvement in Chinese csDMARD-IR RA pts. The safety of UPA was comparable with the overall study population and with the safety seen in the global Phase 3 program.