Journal Article Ahead of print
PubMed: 41991443 DOI: 10.1016/j.ard.2026.03.013
Upadacitinib vs adalimumab in patients with rheumatoid arthritis and a prior inadequate response or intolerance to a tumour necrosis factor inhibitor: 12-week results from the randomised, double-blind, SELECT-SWITCH study.
Ann Rheum Dis
Authors: Eduardo Mysler, Prodromos I Sidiropoulos, Andra Balanescu, Jacqueline Detert, Ricardo M Xavier, Christina Charles-Schoeman, Louis Bessette, Angela Crowley, Yuko Kaneko, Zhuoli Zhang, Orsolya Nagy, Yanxi Liu, Jingchen Ren, Ana B Romero, Jessica L Suboticki, Ryan DeMasi, Sebastian Meerwein, Roy Fleischmann
Affiliations
- Department of Rheumatology, Organización Medica de Investigación, Buenos Aires, Argentina.
- Rheumatology and Clinical Immunology, University of Crete Medical School and "Institute of Molecular Biology and Biotechnology", Foundation for Research and Technology Hellas (FORTH), Heraklion, Greece.
- Department of Internal Medicine and Rheumatology, Sf. Maria Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
- Rheumatological-Immunological Medical Practice, Templin, Germany.
- Division of Rheumatology, Hospital de Clínicas de Porto Alegre/Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
- Division of Rheumatology, University of California, Los Angeles, CA, USA.
- Department of Medicine, Laval University, Québec City, QC, Canada.
- Willow Rheumatology and Wellness, Willowbrook, IL, USA.
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
- Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing, China.
- AbbVie Ltd. Budapest, Hungary.
- AbbVie Inc. North Chicago, IL, USA.
- AbbVie S.L.U. Madrid, Spain.
- AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
- Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Abstract
OBJECTIVES
After the first tumour necrosis factor inhibitor (TNFi) failure, patients with rheumatoid arthritis (RA) often cycle to a second; however, switching mechanisms of action has been postulated to improve outcomes. The ongoing SELECT-SWITCH trial compared upadacitinib with adalimumab for active RA after first TNFi failure at 12 weeks.
METHODS
Patients with inadequate response or intolerance to 1 nonadalimumab TNFi receiving stable methotrexate were randomised (1:1) to 15 mg once daily upadacitinib or 40 mg every-other-weekly adalimumab. The primary endpoint was achieving superiority in Disease Activity Score 28 (DAS28)-C-reactive protein (CRP) ≤3.2 at week 12. Ranked secondary endpoints (week 12, superiority) were (1) achieving ≥50% improvement in American College of Rheumatology response criteria (ACR50); (2) achieving DAS28-CRP <2.6; change from baseline in (3) DAS28-CRP; (4) pain; (5) Health Assessment Questionnaire Disability Index (HAQ-DI).
RESULTS
Overall, 492 patients were randomised. Baseline characteristics were balanced between groups. Week 12 DAS28-CRP ≤3.2 response was superior with upadacitinib (43.3%) vs adalimumab (22.4%; difference, 21.0% [95% CI: 12.9-29.1]; P < .0001) as were ACR50 (38.2% vs 26.8% [P = .0068]), DAS28-CRP <2.6 (28.4% vs 14.5%; P = .0002), mean changes in DAS28-CRP (-2.432 vs -1.840; P < .0001) and pain (-3.165 vs -2.373; P = .0005), but not in HAQ-DI (-0.523 vs -0.496; P = .5849). Safety was comparable between treatments.
CONCLUSIONS
The primary endpoint of the SELECT-SWITCH trial was met, with a higher percentage of patients with active RA who switched to upadacitinib after first TNFi failure achieving DAS28-CRP ≤3.2 at 12 weeks than those cycling to a second TNFi, adalimumab, with generally similar safety profiles.
GOV IDENTIFIER
NCT05814627.
MeSH
Pain, Arthritis, Necrosis, Arthritis, Rheumatoid, Adalimumab