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
Authors: Y. Tanaka, T. Takeuchi, K. Yamaoka, M. Oribe, M. Kawano, Y. Zhou, A.A. Othman, A.L. Pangan, S. Kitamura, N. Matsuda, S. Meerwein, H. Kameda
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Upadacitinib (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.<sup>1–4</sup> <h3>Objectives</h3> To evaluate the efficacy and safety of UPA in Japanese active RA patients with inadequate response to csDMARDs (csDMARD-IR). <h3>Methods</h3> During 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). <h3>Results</h3> Of 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&lt;0.001). A significant difference in ACR20 was observed as early as Week 1 (<b>table 1)</b>. 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 (<b>Table</b>). At Week 12, patients receiving UPA vs PBO had greater improvements from baseline (p&lt;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. <h3>Conclusions</h3> In 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. <h3>References</h3> [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). <h3>Acknowledgements</h3> AbbVie, 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. <h3>Disclosure of Interest</h3> Y. 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 Pharmaceutical Co Ltd, YL Biologics, Eli Lilly Japan KK, Sanofi KK, Janssen Pharmaceutical KK, UCB Japan Co., Ltd, T. Takeuchi Grant/research support from: Pfizer Japan Inc., Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Ltd, AYUMI Pharmaceutical Corporation, Takahashi Industrial and Economic Research Foundation, Paid instructor for: Astellas Pharma Inc., AbbVie GK, Eisai Co., Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, UCB Japan Co., Ltd, Speakers bureau: Mitsubishi-Tanabe Pharma Corporation, Janssen Pharmaceutical KK, Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., AbbVie GK, Eisai Co., Ltd, Bristol-Myers Squibb Company, Daiichi Sankyo Company Ltd, Eli Lilly Japan KK, Pfizer Japan Inc., K. Yamaoka Speakers bureau: Pfizer Japan Inc., Chugai Pharmaceutical Co Ltd, Takeda Pharmaceutical Company Ltd, Astellas Pharma Inc, AbbVie GK, Bristol-Myers Squibb Company, Mitsubishi-Tanabe Pharma Corporation, M. Oribe: None declared, M. Kawano: None declared, Y. Zhou Shareholder of: AbbVie, Employee of: AbbVie, A. Othman Shareholder of: AbbVie, Employee of: AbbVie, A. Pangan Shareholder of: AbbVie, Employee of: AbbVie, S. Kitamura Shareholder of: AbbVie, Employee of: AbbVie, N. Matsuda Shareholder of: AbbVie, Employee of: AbbVie, S. Meerwein Shareholder of: AbbVie, Employee of: AbbVie, H. Kameda Grant/research support from: AbbVie GK, Astellas Pharma Inc, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co Ltd, Mitsubishi-Tanabe Pharma Corporation and Novartis Pharma KK., Speakers bureau: AbbVie GK, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co Ltd, Eli Lilly Japan KK, Janssen Pharmaceutical KK, Mitsubishi-Tanabe Pharma Corporation, Novartis Pharma KK and Sanofi KK