Hideto Kameda1, Tsutomu Takeuchi2, Kunihiro Yamaoka3, Motohiro Oribe4, Mitsuhiro Kawano5, Masayuki Yokoyama6, Aileen L Pangan7, Yuko Konishi6, Sebastian Meerwein8, Yoshiya Tanaka9. 1. Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Toho University, 2-22-36, Ohashi, Meguro-ku, Tokyo, 153-8515, Japan. hideto.kameda@med.toho-u.ac.jp. 2. Keio University School of Medicine, 2 Chome-15-45 Mita, Minato City, Tokyo, 108-8345, Japan. 3. Kitasato University School of Medicine, 1 Chome-15-1 Kitazato, Minami Ward, Sagamihara, Kanagawa, 252-0374, Japan. 4. Department of Internal Medicine, Oribe Clinic of Rheumatism and Medicine, Oita Oita-shi Otemachi 2-1-15, Oita, Japan. 5. Rheumatology, Honjo Rheumatism Clinic, Takaoka, Toyama, 933-0874, Japan. 6. Immunology, AbbVie GK, 16F, 3 Chome-1-14F Shibaura, Minato City, Tokyo, 105-0023, Japan. 7. Immunology, AbbVie, 1400 Sheridan Rd, North Chicago, IL, 60064, USA. 8. Pharmaceutical Development, AbbVie Deutschland GmbH & Co KG, Knollstraße 50, 67061, Ludwigshafen am Rhein, Germany. 9. The First Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi Ward, Kitakyushu, Fukuoka, 807-8555, Japan.
Abstract
BACKGROUND: The objective of the study was to evaluate the efficacy and safety of upadacitinib over 84 weeks in Japanese patients with active rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. METHODS: All patients completing a 12-week, randomized, double-blind treatment period entered a blinded extension and continued upadacitinib 7.5, 15, or 30 mg once daily (QD), or were switched from placebo to upadacitinib 7.5, 15, or 30 mg QD. Efficacy and safety were assessed over 84 weeks. RESULTS:Of 197 randomized patients, 187 (94.9%) completed the 12-week period and entered the blinded extension; 152 (77.2%) patients were ongoing at week 84. At week 84, the proportions of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) were 85.7%, 77.6%, and 58.0% with continued upadacitinib 7.5, 15, and 30 mg, respectively (nonresponder imputation), and were similar in patients who had switched from placebo. Favorable response rates were also observed for more stringent measures of response (ACR50/70) and remission (defined by the Disease Activity Score of 28 joints with C-reactive protein, Clinical Disease Activity Index, or Simplified Disease Activity Index). The 15 mg and 30 mg doses of upadacitinib were associated with more rapid and numerically higher initial responses for some measures of disease activity and remission compared with the 7.5 mg dose. Rates of adverse events, infection, opportunistic infection, serious infection, and herpes zoster were lower with upadacitinib 7.5 and 15 mg versus 30 mg. CONCLUSIONS:Upadacitinib demonstrated sustained efficacy and was well tolerated over 84 weeks in Japanese patients with RA, with upadacitinib 15 mg offering the most favorable benefit-risk profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT02720523 . Registered on March 22, 2016.
RCT Entities:
BACKGROUND: The objective of the study was to evaluate the efficacy and safety of upadacitinib over 84 weeks in Japanese patients with active rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. METHODS: All patients completing a 12-week, randomized, double-blind treatment period entered a blinded extension and continued upadacitinib 7.5, 15, or 30 mg once daily (QD), or were switched from placebo to upadacitinib 7.5, 15, or 30 mg QD. Efficacy and safety were assessed over 84 weeks. RESULTS: Of 197 randomized patients, 187 (94.9%) completed the 12-week period and entered the blinded extension; 152 (77.2%) patients were ongoing at week 84. At week 84, the proportions of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) were 85.7%, 77.6%, and 58.0% with continued upadacitinib 7.5, 15, and 30 mg, respectively (nonresponder imputation), and were similar in patients who had switched from placebo. Favorable response rates were also observed for more stringent measures of response (ACR50/70) and remission (defined by the Disease Activity Score of 28 joints with C-reactive protein, Clinical Disease Activity Index, or Simplified Disease Activity Index). The 15 mg and 30 mg doses of upadacitinib were associated with more rapid and numerically higher initial responses for some measures of disease activity and remission compared with the 7.5 mg dose. Rates of adverse events, infection, opportunistic infection, serious infection, and herpes zoster were lower with upadacitinib 7.5 and 15 mg versus 30 mg. CONCLUSIONS:Upadacitinib demonstrated sustained efficacy and was well tolerated over 84 weeks in Japanese patients with RA, with upadacitinib 15 mg offering the most favorable benefit-risk profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT02720523 . Registered on March 22, 2016.
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