TOPLINE:

Switching to upadacitinib after failure of a first TNF inhibitor resulted in superior disease control compared with cycling to adalimumab in patients with rheumatoid arthritis (RA). At 12 weeks, more patients receiving upadacitinib achieved low disease activity, with comparable safety profiles between treatments.

METHODOLOGY:

• Researchers conducted a randomized phase 3b/4 trial across 218 sites in 24 countries to determine whether switching to a JAK inhibitor or cycling to another TNF inhibitor would be more efficacious for patients with active RA who previously had an inadequate response or intolerance to a single non-adalimumab TNF inhibitor while receiving stable methotrexate.
• A total of 491 patients (mean age, 55.6 years; 77.4% female) were randomly assigned to receive either 15 mg of upadacitinib orally once daily plus a placebo matching adalimumab (n = 245) or 40 mg of adalimumab subcutaneously every other week plus a placebo matching upadacitinib (n = 246) during a 12-week, double-blind period.
• Patients had active RA with at least six swollen joints out of the 66 assessed, at least six tender joints out of the 68 assessed, and a high-sensitivity C-reactive protein (CRP) level ≥ 3 mg/L at screening or baseline. The mean disease duration was 10.18 years.
• The primary endpoint was achievement of a Disease Activity Score in 28 joints using CRP (DAS28-CRP) ≤ 3.2 at week 12.
• Secondary endpoints included achieving a ≥ 50% improvement in the American College of Rheumatology response criteria (ACR50) and changes in pain, the Health Assessment Questionnaire Disability Index, and the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, among others. Safety was monitored through treatment-emergent adverse events (TEAEs).

TAKEAWAY:

• At week 12, upadacitinib demonstrated superiority over adalimumab in achieving DAS28-CRP ≤ 3.2 (43.3% vs 22.4% of patients; difference, 21.0%; P < .0001).
• Upadacitinib was more effective than adalimumab in terms of achieving an ACR50 response (38.2% vs 26.8% of patients; difference, 11.4%; P = .0068), change in DAS28-CRP from baseline (difference, -0.593; P < .0001), and patients’ assessment of improvement in pain from baseline (difference, -0.792; P = .0005).
• A greater proportion of patients receiving upadacitinib vs adalimumab achieved DAS28 (using erythrocyte sedimentation rate) ≤ 3.2, Clinical Disease Activity Index ≤ 10, and Simple Disease Activity Index ≤ 11 (nominal P < .0001 for all). The least squares mean change in FACIT-Fatigue was also greater in patients receiving upadacitinib vs adalimumab (nominal P = .0363).
• TEAEs occurred in 41.6% of upadacitinib-treated patients and 40.8% of adalimumab-treated patients, with serious adverse events in 2.0% and 2.4%, respectively. No deaths, active tuberculosis, major adverse cardiovascular events, adjudicated gastrointestinal perforations, or venous thromboembolic events were reported in either group.

IN PRACTICE:

“Identifying patients who would benefit from switching [mechanism of action] vs cycling to another TNFi [TNF inhibitor] is essential, and the benefit-risk profile of UPA [upadacitinib] should be carefully considered in the context of any existing comorbidities or cardiovascular risk factors before undertaking any personalized treatment decisions,” the authors of the study wrote. “SELECT-SWITCH is ongoing, and forthcoming long-term data will provide a more comprehensive understanding of the sustained efficacy and safety of switching to UPA vs cycling to a second TNFi after first TNFi failure.”

SOURCE:

The study was led by Eduardo Mysler, MD, Organización Medica de Investigación, Buenos Aires, Argentina. It was published online on April 15, 2026, in Annals of the Rheumatic Diseases.

LIMITATIONS:

Only patients with RA were included, and those with serious other health issues were excluded. The patients had long mean disease duration, experienced significant inflammation, and had difficulties in daily activities; this may not be typical for all patients with RA in clinical practice. Comparing upadacitinib with just one TNF inhibitor may affect the generalizability of the findings.

DISCLOSURES:

AbbVie provided funding for this study and was involved in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. Several authors disclosed receiving or having pending grants and receiving honoraria, consulting fees, and payments for lectures, which includes service on speakers bureaus from various pharmaceutical companies, including AbbVie, GSK, Novartis, Pfizer, and others. Some authors reported being investigators in clinical trials sponsored by various pharmaceutical companies. Seven authors reported being employees of AbbVie and may hold stock and/or options in the company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.