Upadacitinib versus placebo or adalimumab with background methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate: a subgroup analysis of a phase III randomized controlled trial in Central and Eastern European patients

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Authors
Karel Pavelka MD PhD, Zoltán Szekanecz MD PhD DSc, Nemanja Damjanov MD PhD, Branimir Anić MD PhD, Matija Tomšič MD PhD, Vadim Mazurov MD PhD, Marija Maksimovic MD, Orsolya Nagy MD PhD, Jerzy Świerkot MD PhD, Tzvetanka Petranova MD PhD, Tiina Veldi MD, Asta Baranauskaitė MD PhD, Catalin Codreanu MD PhD, Daina Andersone MD PhD, Roy Fleischmann MD

Article Type
Original Research

DOI
10.7573/dic.2020-7-5

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Abstract

Background: In the randomized, phase III, global SELECTCOMPARE study, upadacitinib 15 mg demonstrated efficacy at week 12 versus placebo and adalimumab with methotrexate (MTX) in patients with rheumatoid arthritis and inadequate response to MTX, which was maintained over 48 weeks. This post hoc analysis of SELECT-COMPARE reports the efficacy and safety of upadacitinib in Central and Eastern European (CEE) patients.

Methods: Patients were randomized 2:2:1 to upadacitinib 15 mg once daily, placebo, or adalimumab 40 mg every other week, and continued MTX. Efficacy and safety were assessed through 48 weeks. Primary endpoints were the achievement of ≥20% improvement in American College of Rheumatology response criteria and Disease Activity Score in 28 joints with C-reactive protein <2.6 responses at week 12 for upadacitinib versus placebo. No statistical comparisons were conducted.

Results: A total of 596 patients from 12 CEE countries were randomized. At week 12, a numerically greater proportion of patients receiving upadacitinib versus placebo or adalimumab achieved ≥20% improvement in American College of Rheumatology response criteria (72% versus 33% and 59%), Disease Activity Score in 28 joints with C-reactive protein <2.6 (26% versus 4% and 11%), low disease activity and remission, and improved physical function, with results maintained over 48 weeks. Upadacitinib treatment numerically inhibited structural progression versus placebo at week 26. Serious infection and herpes zoster rates were numerically higher with upadacitinib versus adalimumab (2.7 versus 1.7 and 2.3 versus 1.1 events/100 patient-years, respectively) over 48 weeks.

Conclusion: Consistent with the global population of patients with rheumatoid arthritis and an inadequate response to MTX, in CEE patients, upadacitinib 15 mg demonstrated clinical and functional improvements versus placebo and adalimumab, radiographic improvements versus placebo, and reasonable safety, over 48 weeks.

Keywords: Eastern Europe, rheumatoid arthritis, safety, treatment efficacy, upadacitinib.

Citation: Pavelka K, Szekanecz Z, Damjanov N, Anić B, Tomšič M, Mazurov V, Maksimovic M, Nagy O, Świerkot J, Petranova T, Veldi T, Baranauskaitė A, Codreanu C, Andersone D, Fleischmann R. Upadacitinib versus placebo or adalimumab with background methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate: a subgroup analysis of a phase III randomized controlled trial in Central and Eastern European patients. Drugs in Context 2020; 9: 2020-7-5. DOI: 10.7573/dic.2020-7-5

Trial registration number: NCT02629159.

Contributions: Karel Pavelka and Zoltán Szekanecz should be considered joint first authors. The design and study conduct for the clinical trial were provided by AbbVie. Roy Fleischmann, Karel Pavelka, Zoltán Szekanecz, and Orsolya Nagy contributed substantially to the conception and design of the work. All contributed substantially to the acquisition, analysis, and interpretation of data for the work. Roy Fleischmann, Karel Pavelka, Zoltán Szekanecz, and Orsolya Nagy contributed substantially to drafting of the manuscript and revising it critically for important intellectual content. All provided final approval of the version to be published.

Disclosure and potential conflicts of interest: Karel Pavelka has received honoraria from AbbVie, Amgen, BMS, Egis, Hospira, Medac, MSD, Pfizer, Roche, and UCB. Zoltán Szekanecz has received consulting fees and honoraria from AbbVie, Amgen, BMS, Gedeon Richter, Lilly, MSD, Pfizer, Roche, Sanofi, and UCB. Nemanja Damjanov has received grants and research support from AbbVie, Pfizer, and Roche, and consulting fees and honoraria from AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche. Branimir Anić has nothing to disclose. Matija Tomšič has received research grants, consulting fees, and honoraria from AbbVie, Amgen, Biogen, Celltrion, Lilly, Novartis, Pfizer, Roche, and Sanofi. Vadim Mazurov has nothing to disclose. Marija Maksimovic and Orsolya Nagy are employees of AbbVie Ltd and may own AbbVie stock. Jerzy Świerkot has received honoraria from AbbVie, Amgen, BMS, Egis, Gedeon Richter, Lilly, MSD, Pfizer, Roche, Novartis, and UCB. Tzvetanka Petranova has received consulting fees and honoraria from AbbVie, Amgen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB. Tiina Veldi has nothing to disclose. Asta Baranauskaitė has received research funding, consulting fees, and honoraria from AbbVie. Catalin Codreanu has received consulting fees and honoraria from AbbVie, Amgen, BMS, Egis, MSD, Pfizer, Roche, Sanofi, and UCB. Daina Andersone has received grants and consulting fees from AbbVie, Amgen, BMS, Janssen, Novartis, Pfizer, and Roche. Roy Fleischmann has received grants and consulting fees from AbbVie, Amgen, BMS, Gilead, Lilly, Novartis, and Pfizer, and grants from EMD-Serono, Genentech, Roche, Sanofi, and UCB. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2020/09/dic.2020-7-5-COI.pdf

Acknowledgements: 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. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in these studies. They would also like to thank In-Ho Song, Medical Director, Immunology Clinical Development, AbbVie, for his input, and Yanna Song, Senior Research Statistician, AbbVie, for conducting the statistical analysis. Medical writing support was provided by Hilary Wong, PhD, of 2 the Nth (Cheshire, UK), funded by AbbVie.

Funding declaration: This work was supported by AbbVie. AbbVie contributed to study design, data collection, analysis and interpretation, and to writing, reviewing, and approval of final version. AbbVie also provided funding for medical writing support by Hilary Wong, PhD, of 2 the Nth (Cheshire, UK).

Copyright: Copyright © 2020 Pavelka K, Szekanecz Z, Damjanov N, Anić B, Tomšič M, Mazurov V, Maksimovic M, Nagy O, Jerzy Świerkot J, Petranova T, Veldi T, Asta Baranauskaitė A, Codreanu C, Andersone D, Fleischmann R. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2020 Pavelka K, Szekanecz Z, Damjanov N, Anić B, Tomšič M, Mazurov V, Maksimovic M, Nagy O, Jerzy Świerkot J, Petranova T, Veldi T, Asta Baranauskaitė A, Codreanu C, Andersone D, Fleischmann R. https://doi.org/10.7573/dic.2020-7-5. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/upadacitinib-versus-placebo-or-adalimumab-with-background-methotrexate-in-patients-with-rheumatoid-arthritis-and-an-inadequate-response-to-methotrexate

Correspondence: Karel Pavelka, Institute of Rheumatology and Department of Rheumatology, Charles University, Na Slupi 4, 128 50 Prague 2, Czech Republic. pavelka@revma.cz

Provenance: submitted; externally peer reviewed.

Submitted: 22 July 2020; Peer review comments to author: 22 August 2020; Revised manuscript received: 9 September 2020; Accepted: 11 September 2020; Publication date: 19 October 2020.

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