Efficacy and safety of upadacitinib over 84 weeks in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE)

Hideto Kameda, Tsutomu Takeuchi, Kunihiro Yamaoka, Motohiro Oribe, Mitsuhiro Kawano, Masayuki Yokoyama, Aileen L Pangan, Yuko Konishi, Sebastian Meerwein, Yoshiya Tanaka, Hideto Kameda, Tsutomu Takeuchi, Kunihiro Yamaoka, Motohiro Oribe, Mitsuhiro Kawano, Masayuki Yokoyama, Aileen L Pangan, Yuko Konishi, Sebastian Meerwein, Yoshiya Tanaka

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.

Keywords: Janus kinase inhibitor; Japanese; Rheumatoid arthritis; Upadacitinib.

Conflict of interest statement

Hideto Kameda: Consulting fees, speaking fees, and/or honoraria: AbbVie GK, Asahi-Kasei, Bristol-Myers Squibb, Chugai, Eli Lilly Japan K.K., Gilead, Janssen K.K., Mitsubishi-Tanabe, Novartis, Pfizer Japan, Sanofi K.K., and UCB Japan. Research grants: AbbVie GK, Asahi-Kasei, Astellas, Chugai, Eisai, Mitsubishi-Tanabe, and Novartis.

Tsutomu Takeuchi: Personal fees: AbbVie GK, Astellas, AYUMI, Bristol-Myers Squibb K.K., Boehringer-Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly Japan K.K., Gilead, GlaxoSmithKline K.K., Janssen K.K., Mitsubishi-Tanabe, Novartis K.K., Nipponkayaku, Pfizer Japan, Sanofi K.K., Taiho, Taisho, and UCB Japan. Grants: AbbVie GK, Asahi-Kasei, Astellas, AYUMI, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Nipponkayaku, Novartis K.K., Pfizer Japan, Shionogi & Co., and Takeda. Speaker fees: AbbVie GK, Astellas, AYUMI, Chugai, Daiichi-Sankyo, Eisai, Gilead, Mitsubishi-Tanabe, Novartis K.K., Pfizer Japan, Sanofi K.K., Takeda, and Teijin. Consultant fees: Astellas, Boehringer-Ingelheim, Chugai, Janssen K.K., Mitsubishi-Tanabe, Nipponkayaku, Taiho, Taisho Toyama, and UCB Japan.

Kunihiro Yamaoka: Speakers bureau: AbbVie GK, Astellas, Bristol-Myers Squibb, Chugai, Mitsubishi-Tanabe, Pfizer Japan, and Takeda.

Motohiro Oribe and Mitsuhiro Kawano: None declared.

Masayuki Yokoyama, Aileen L Pangan, Yuko Konishi, and Sebastian Meerwein: Employees of AbbVie and may own stock or options.

Yoshiya Tanaka: Speaking fees and/or honoraria: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Takeda, Teijin, and YL Biologics. Research grants: Asahi-Kasei, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Ono, Sanofi, Takeda, and UCB.

Figures

Fig. 1
Fig. 1
Patient disposition in periods 1 (12-week, placebo-controlled) and 2 (blinded extension; cut-off December 26, 2018). AE, adverse event
Fig. 2
Fig. 2
a ACR20, b ACR50, and c ACR70 responses over 84 weeks (full analysis set; NRI). ACR20/50/70, 20/50/70% improvement in American College of Rheumatology criteria; NRI, nonresponder imputation; QD, once daily
Fig. 3
Fig. 3
Proportions of patients achieving low disease activity and remission over 84 weeks, respectively based on a, b DAS28(CRP) (≤ 3.2 and < 2.6), c, d CDAI (≤ 10 and ≤ 2.8), and e, f SDAI (≤ 11 and ≤ 3.3) (full analysis set; NRI). CDAI, Clinical Disease Activity Index; DAS28(CRP), Disease Activity Score of 28 joints with C-reactive protein; NRI, nonresponder imputation; QD, once daily; SDAI, Simplified Disease Activity Index
Fig. 4
Fig. 4
Proportions of patients reporting minimal clinically important improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI decrease from baseline of ≥ 0.22) over 84 weeks (full analysis set; NRI). NRI, nonresponder imputation; QD, once daily

References

    1. Alunno A, Padjen I, Fanouriakis A, Boumpas DT. Pathogenic and therapeutic relevance of JAK/STAT signaling in systemic lupus erythematosus: integration of distinct inflammatory pathways and the prospect of their inhibition with an oral agent. Cells. 2019;8(8):898. doi: 10.3390/cells8080898.
    1. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet. 2017;389(10086):2328–2337. doi: 10.1016/S0140-6736(17)31472-1.
    1. O'Shea J, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013;72(Suppl 2):ii111–ii115. doi: 10.1136/annrheumdis-2012-202576.
    1. Kameda H, Fujii T, Nakajima A, Koike R, Sagawa A, Kanbe K, et al. Japan College of Rheumatology guideline for the use of methotrexate in patients with rheumatoid arthritis. Mod Rheumatol. 2019;29(1):31–40. doi: 10.1080/14397595.2018.1472358.
    1. Singh JA, Saag KG, Bridges SL, Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1–26. doi: 10.1002/art.39480.
    1. Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685–699. doi: 10.1136/annrheumdis-2020-217811.
    1. Taylor PC. Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis. Rheumatology (Oxford) 2019;58(Suppl 1):i17–i26. doi: 10.1093/rheumatology/key225.
    1. Harigai M. Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis. Rheumatology (Oxford) 2019;58(Suppl 1):i34–i42. doi: 10.1093/rheumatology/key287.
    1. Tanaka Y, Ishii T, Cai Z, Schlichting D, Rooney T, Macias W. Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: a 52-week, randomized, single-blind, extension study. Mod Rheumatol. 2018;28(1):20–29. doi: 10.1080/14397595.2017.1307899.
    1. Yamanaka H, Tanaka Y, Takeuchi T, Sugiyama N, Yuasa H, Toyoizumi S, et al. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study. Arthritis Res Ther. 2016;18:34. doi: 10.1186/s13075-016-0932-2.
    1. Kameda H, Takeuchi T, Yamaoka K, Oribe M, Kawano M, Zhou Y, et al. Efficacy and safety of upadacitinib in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE): a placebo-controlled phase IIb/III study. Rheumatology (Oxford) 2020:[Epub ahead of print].
    1. Summary of treatment-emergent adverse. 2018;2:23.
    1. Genovese MC, Smolen JS, Weinblatt ME, Burmester GR, Meerwein S, Camp HS, et al. Efficacy and safety of ABT-494, a selective JAK-1 inhibitor, in a phase IIb study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Rheumatol. 2016;68(12):2857–2866. doi: 10.1002/art.39808.
    1. Kremer JM, Emery P, Camp HS, Friedman A, Wang L, Othman AA, et al. A phase IIb study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to anti-tumor necrosis factor therapy. Arthritis Rheumatol. 2016;68(12):2867–2877. doi: 10.1002/art.39801.
    1. Burmester GR, Kremer JM, Van den Bosch F, Kivitz A, Bessette L, Li Y, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503–2512. doi: 10.1016/S0140-6736(18)31115-2.
    1. Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double-blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788–1800. doi: 10.1002/art.41032.
    1. Genovese MC, Fleischmann R, Combe B, Hall S, Rubbert-Roth A, Zhang Y, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513–2524. doi: 10.1016/S0140-6736(18)31116-4.
    1. Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019;393(10188):2303–2311. doi: 10.1016/S0140-6736(19)30419-2.
    1. Takeuchi T, van Vollenhoven R, Pangan AL, Friedman A, Mohamed ME, Chen S, et al. A phase 3, randomized controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX-naïve patients with active rheumatoid arthritis [Abstract W38–2] Mod Rheumatol. 2019;29:S118. doi: 10.1080/14397595.2018.1553489.

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