BACKGROUND: In the randomized, phase III, global SELECT-COMPARE 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.

AbbVie Biopharmaceuticals GmbH Belgrade Serbia

AbbVie Global Medical Affairs Rheumatology Budapest Hungary

Center of Rheumatic Diseases University of Medicine and Pharmacy Bucharest Romania

Department of Rheumatology and Internal Medicine Wroclaw Medical University Wroclaw Poland

Department of Rheumatology Lithuanian University of Health Sciences Kaunas Lithuania

Department of Rheumatology UMHAT St Iv Rilsky Medical University Sofia Bulgaria

Department of Rheumatology University Medical Centre Ljubljana Ljubljana Slovenia

Division of Clinical Immunology and Rheumatology Department of Internal Medicine University of Zagreb School of Medicine Zagreb Croatia

Division of Rheumatology Faculty of Medicine University of Debrecen Debrecen Hungary

East Tallinn Central Hospital Tallinn Estonia

Institute of Rheumatology and Department of Rheumatology Charles University Prague Czech Republic

North Western State Medical University named after 1 I Mechnikov St Petersburg Russia

P Stradins Clinical University Hospital Riga Latvia

University of Belgrade School of Medicine Institute of Rheumatology Belgrade Serbia

University of Texas Southwestern Medical Center Metroplex Clinical Research Center Dallas TX USA

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Smolen JS, Landewé RBM, Bijlsma JWJ, 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-2019-216655. PubMed DOI

Singh JA, Saag KG, Bridges SL, Jr, et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2016;68(1):1–25. doi: 10.1002/acr.22783. PubMed DOI

AbbVie. Rinvoq (upadacitinib) [package insert] European Medicines Agency website. [Accessed April 29, 2020]. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.

Burmester GR, Kremer JM, Van den Bosch F, 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. PubMed DOI

Genovese MC, Fleischmann R, Combe B, 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. PubMed DOI

van Vollenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and safety of upadacitinib monotherapy in methotrexate-naïve patients with moderately to severely active rheumatoid arthritis (SELECT-EARLY): a randomized, double-blind, active-comparator, multi-center, multi-country trial. Arthritis Rheumatol. 2020;72(10):1607–1620. doi: 10.1002/art.41384. PubMed DOI PMC

Fleischmann R, Pangan AL, Song IH, 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. PubMed DOI

Smolen JS, Pangan AL, Emery P, 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. PubMed DOI

Kameda H, Takeuchi T, Yamaoka K, 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. p. keaa084. PubMed DOI PMC

AbbVie. Rinvoq (upadacitinib) [package insert] US Food and Drug Administration website. [Accessed April 29, 2020]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211675s000lbl.pdf.

Fleischmann RM, Genovese MC, Enejosa JV, et al. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis. 2019;78(11):1454–1462. doi: 10.1136/annrheumdis-2019-215764. PubMed DOI PMC

Wollenhaupt J, Lee EB, Curtis JR, et al. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther. 2019;21(1):89. doi: 10.1186/s13075-019-1866-2. PubMed DOI PMC

Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 7 years: an updated integrated safety analysis. Ann Rheum Dis. 2019;78:308–309. doi: 10.1136/annrheumdis-2019-eular.691. (Abstract THU0078). DOI

Cohen SB, van Vollenhoven R, Winthrop K, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the select phase 3 clinical program. Ann Rheum Dis. 2019;78:357. doi: 10.1136/annrheumdis-2019-eular.3403. (Abstract THU0167). PubMed DOI PMC

Batko B, Stajszczyk M, Swierkot J, et al. Prevalence and clinical characteristics of rheumatoid arthritis in Poland: a nationwide study. Arch Med Sci. 2019;15(1):134–140. doi: 10.5114/aoms.2017.71371. PubMed DOI PMC

Kaló Z, Vokó Z, Östör A, et al. Patient access to reimbursed biological disease-modifying antirheumatic drugs in the European region. J Mark Access Health Policy. 2017;5(1) doi: 10.1080/20016689.2017.1345580. 1345580. PubMed DOI PMC

Kawalec P, Tesar T, Vostalova L, et al. Pharmaceutical regulation in Central and Eastern European countries: a current review. Front Pharmacol. 2017;8:892. doi: 10.3389/fphar.2017.00892. PubMed DOI PMC

Tuckwell K, Teng E, Chia J, et al. Adverse event reporting rates and placebo/standard-of-care-arm American College of Rheumatology responses vary by region in rheumatoid arthritis trials. [Accessed April 29, 2020];Arthritis Rheumatol. 2018 70 Abstract 269. https://acrabstracts.org/abstract/adverse-event-reporting-rates-and-placebo-standard-of-care-arm-american-college-of-rheumatology-responses-vary-by-region-in-rheumatoid-arthritis-trials/ PubMed PMC

Bechman K, Yates M, Norton S, et al. Placebo response in rheumatoid arthritis clinical trials. J Rheumatol. 2020;47(1):28–34. doi: 10.3899/jrheum.190008. PubMed DOI PMC

van der Heijde D, van Leeuwen MA, van Riel PLCM, et al. Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum. 1992;35(1):26–34. doi: 10.1002/art.1780350105. PubMed DOI

van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol. 2000;27(1):261–263. PubMed

Sepriano A, Kerschbaumer A, Smolen JS, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2020 doi: 10.1136/annrheumdis-2019-216653. PubMed DOI

Winthrop KL, Yamanaka H, Valdez H, et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014;66(10):2675–2684. doi: 10.1002/art.38745. PubMed DOI PMC

Harigai M, Takeuchi T, Smolen JS, et al. Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment: an integrated analysis of phases 2 and 3 trials. Mod Rheumatol. 2020;30(1):36–43. doi: 10.1080/14397595.2019.1583711. PubMed DOI

Pfizer. Xeljanz (tofacitinib) [package insert] European Medicines Agency website. [Accessed April 29, 2020]. https://www.ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_en.pdf.

EMA website. EMA confirms Xeljanz to be used with caution in patients at high risk of blood clots. [Accessed April 29, 2020]. https://www.ema.europa.eu/en/documents/referral/xeljanz-article-20-procedure-ema-confirms-xeljanz-be-used-caution-patients-high-risk-blood-clots_en.pdf.

Eli Lilly. Olumiant (baricitinib) [package insert] European Medicines Agency website. [Accessed April 29, 2020]. https://www.ema.europa.eu/en/documents/product-information/olumiant-epar-product-information_en.pdf.