SAT0257 A phase 2b/3 randomised, placebo-controlled, double-blind study of upadacitinib, a selective jak1 inhibitor, in japanese patients with active rheumatoid arthritis and inadequate response to conventional synthetic dmards

Abstract

BackgroundUpadacitinib (UPA) is an oral, JAK1-selective inhibitor found to be effective in Phase 2 and 3 studies in rheumatoid arthritis (RA) patients with inadequate response or intolerance to csDMARDs and bDMARDs.1–4 ObjectivesTo evaluate the efficacy and safety of UPA in Japanese active RA patients with inadequate response to csDMARDs (csDMARD-IR).MethodsDuring the 12 week double-blind period, patients on stable csDMARDs were randomised to receive UPA 7.5,15 or 30 mg once daily or PBO (1:1:1:1). The primary endpoint was proportion of patients achieving ACR20 at Wk 12 (NRI).ResultsOf 197 patients treated, 187 completed the double-blind period. At Week 12, more patients receiving UPA 7.5, 15 and 30 mg vs PBO met ACR20 (75.5%, 83.7%,80% vs 42.9%, p<0.001). A significant difference in ACR20 was observed as early as Week 1 (table 1). The more stringent responses, such as ACR50/70, DAS28-CRP≤3.2, were achieved by significantly higher proportions of patients on UPA vs PBO with more patients on UPA 15 mg and 30 mg achieving these responses vs UPA 7.5 mg (Table). At Week 12, patients receiving UPA vs PBO had greater improvements from baseline (p<0.001) in DAS28-CRP (−2.08,–2.39, −2.41 vs −0.79) and HAQ-DI (−0.41,–0.45, −0.49 vs −0.10).Overall adverse events (AE), serious AEs, infections (including serious infections, opportunistic infections and herpes zoster) were numerically higher in UPA 30 mg. There were no events of pulmonary embolism, deep vein thrombosis, tuberculosis or malignancy and there were no deaths. Mean haemoglobin levels improved with UPA 7.5 (+0.35 g/dL) and remained stable with UPA 15 (-0.03 g/dL) vs UPA 30 (-0.54 g/dL) and PBO (−0.17 g/dL). CPK elevations and lymphopenia occurred more frequently in UPA 30 mg.ConclusionsIn this Japanese RA csDMARD-IR population, the efficacy of UPA was demonstrated, with better responses for more stringent endpoints on UPA 15 mg and 30 mg vs 7.5 mg. The frequency of overall AEs was numerically higher in UPA 30 mg. Overall, safety and tolerability were consistent with Phase 2 and 3 studies to date.References[1] Burmester, et al. Arth Rheum2017;69:S10.[2] Genovese, et al. Arth Rheum2017;69:S10.[3] Kremer, et al. Arth Rheum2016;68(12).[4] Genovese, et al. Arth Rheum2016;68(12).AcknowledgementsAbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis and interpretation, and to writing, reviewing, and approval of final version. Statistical support: Masuyuki Yokoyama, Medical writing support:Naina Barretto, both employees of AbbVie.Disclosure of InterestY. Tanaka Grant/research support from: Mitsubishi-Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc, AbbVie GK, MSD K.K., Daiichi Sankyo Company Ltd, Pfizer Japan Inc., Kyowa Hakko Kirin Co., Ltd, Eisai Co., Ltd, Ono Pharmaceutical Co., Ltd, Speakers bureau: Daiichi Sankyo Company Ltd, Astellas Pharma Inc, Pfizer Japan Inc., Mitsubishi-Tanabe Pharma Corporation, Bristol-Myers Squibb Company, Chugai Phar...

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