Upadacitinib monotherapy versus methotrexate monotherapy in methotrexate-naïve Japanese patients with rheumatoid arthritis: a sub-analysis of the Phase 3 SELECT-EARLY study

Abstract

Objective

To assess upadacitinib monotherapy versus methotrexate (MTX) in MTX-naïve Japanese patients with rheumatoid arthritis (RA) from the Phase 3 SELECT-EARLY study.

Methods

Japanese patients were randomized 2:1:1:1 to upadacitinib 7.5, 15, or 30 mg daily or MTX 7.5 mg/week (titrated to ≤15 mg/week). Efficacy endpoints included the proportion of patients reporting 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 and change from baseline in modified Total Sharp Score (mTSS) at week 24. Other efficacy outcomes were also assessed at weeks 12 and/or 24. Safety was assessed over 24 weeks.

Results

Of 138 Japanese patients enrolled, significantly more patients treated with upadacitinib 7.5 and 15 mg, but not 30 mg, reported ACR20 responses versus MTX at week 12. Significantly smaller changes from baseline in mTSS were observed with upadacitinib 15 and 30 mg, but not 7.5 mg, versus MTX at week 24. Upadacitinib demonstrated an acceptable safety profile; herpes zoster occurred in 3.6%, 7.4%, and 7.1% of patients treated with upadacitinib 7.5, 15, and 30 mg, respectively.

Conclusion

Similar to the global study population, upadacitinib demonstrated clinical efficacy superior to placebo in the Japanese subpopulation. Among upadacitinib-treated patients, herpes zoster was least common with 7.5 mg.

Keywords:

• DMARD
• Japan
• methotrexate
• rheumatoid arthritis
• upadacitinib

Acknowledgments

AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD and Frances Smith, PhD of 2 the Nth (Cheshire, UK), and was funded by AbbVie.

Conflict of interest

T Takeuchi has received grants from AbbVie GK, Asahi-Kasei Pharma Corporation, Astellas Pharma Inc., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., JCR Pharma Co, Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co. Ltd., and Takeda Pharmaceutical Co., Ltd. Personal/speaker fees from A2 Healthcare Corporation, AbbVie GK., Astellas Pharma Inc., AYUMI Pharmaceutical Corporation, Boehringer-Ingelheim Co. Ltd., Bristol-Myers K.K., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Kissei Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Pfizer Japan Inc., SRL. Inc., Taiho Pharmaceutical Co. Ltd., Taisho Pharmaceutical Co. Ltd., and the Uehara Memorial Foundation. Consultancy fees from A2 Healthcare Corporation, AbbVie GK., Astellas Pharma Inc., Boehringer-Ingelheim Co. Ltd., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Gilead Sciences Inc., Nippon Kayaku Co., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., and Taisho Pharmaceutical Co. Ltd. M Rischmueller has received research grants from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, and UCB; consulting/speaker fees from AbbVie, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Gilead, Janssen Cilag, Novartis, Pfizer, Sanofi, and UCB. R Blanco has received grants/research support from AbbVie, MSD, and Roche; consulting fees/participation in company-sponsored speaker’s bureau from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Sharp & Dohme, Pfizer, and Roche. RM Xavier has received consultant/speaker fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and Roche; research grants from AbbVie, Eli Lilly, Janssen, and Pfizer. Y Ueki has received speaker fees from AbbVie GK, Asahi Kasei Pharma Corp., Astellas Pharma Inc., Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd. T Atsumi has received research grants and/or honoraria for meetings from AbbVie Inc., Alexion Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co. Ltd., Eisai, Eli Lilly Japan K.K., Gilead Sciences Inc., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Co., Ltd., and UCB Japan Co. Ltd. S Chen, A Friedman, and AL Pangan are all employees of AbbVie and may hold stock or options. V Strand is a consultant for AbbVie, Amgen, Arena, Asana, AstraZeneca, Bayer, Blackrock, Bioventus, BMS, Boehringer Ingelheim, Celgene, Celltrion, Concentric Analgesics, Crescendo/Myriad Genetics, EMD Serono, Equilium, Eupraxia, Flexion, Galapagos, Genentech/Roche, Gilead, GSK, Horizon, Ichnos, Inmedix, Janssen, Kiniksa, Kypha, Lilly, Merck, MiMedx, MyoKardia, Novartis, Pfizer, Regeneron, Samsung, Samumed, Sandoz, Sanofi, Servier, Setpoint, SKK, Tonix, and UCB. RF van Vollenhoven has received research support (institutional grants) from BMS, GSK, Lilly, and UCB; support for educational programs (institutional grants) from Pfizer and Roche. Consultancy, for which institutional and/or personal honoraria were received from AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Galapagos, Gilead, Janssen, Pfizer, Servier, and UCB. Speaker, for which institutional and/or personal honoraria were received from AbbVie, Galapagos, Janssen, Pfizer, and UCB.

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