Work

Safety of JAK inhibitors versus other biologic therapies following anti-TNF failure in patients with rheumatoid arthritis

Year: 2025

Type: article

Abstract: Treatment of rheumatoid arthritis (RA) frequently requires Janus kinase inhibitors (JAKi) and biologic DMARDs (bDMARDs) with other mechanisms of action (OMA) after tumour necrosis factor inhibitors (TNFi) failure. Comparative safety data between JAKis and OMA in TNFi-inadequate responders (TNFi-IR) remain limited. To evaluate and compare safety profiles of JAKis versus OMA in TNFi-IR RA patients. A retrospective cohort study followed 305 RA patients (163 JAKis; 142 OMA) previously treated with TNFi for up to 24 months. Incidence rates (IR) of adverse events (AEs) per 100 patient-years (PY) and incidence rate ratios (IRR) adjusted for disease activity and previous bDMARD exposure were calculated using Poisson regression. At baseline, OMA patients had higher disease activity (DAS28-CRP = 4.5 vs. 3.8), whereas comorbidities and other baseline characteristics were similar. Overall, AE incidence was higher with OMA (IR 111.6/100 PY) compared to JAKis (IR 65.3/100 PY; adjusted IRR 1.67, 95% CI 1.22–2.31). Serious AEs occurred more frequently with OMA (IR 11.7/100 PY) versus JAKis (IR 7.9/100 PY; adjusted IRR 0.41, 95% CI 0.18–0.95). Infection rates were comparable; herpes zoster occurred exclusively in the JAKi group during the initial year. Venous thromboembolism, cardiovascular events, and malignancies were rare and similar between groups. In RA patients with inadequate response to TNFis, JAKis and OMA showed comparable safety profiles over 24 months. Serious AEs were numerically higher with OMA; herpes zoster was more frequent with JAKis. No new significant safety signals emerged. What is already known on this topic • Janus kinase inhibitors (JAKis) and non-TNF biologic DMARDs (OMA) are increasingly prescribed for RA patients who have an inadequate response to TNF inhibitors, though comparative safety data between these drug classes are limited. What this study adds • This study provides direct comparative evidence on the safety profiles of JAKis versus OMA in RA patients with inadequate response to TNFi, demonstrating similar overall safety outcomes, albeit highlighting differences in the timing and frequency of specific adverse events, such as herpes zoster infections with JAKis and serious adverse events with OMA. How this study might affect research, practice, or policy • These results reinforce existing guidelines advocating for individualised therapeutic choices based on patient-specific risk factors and suggest the continued need for careful patient monitoring, particularly for infections and serious adverse events, guiding clinicians in selecting appropriate therapies after TNFi failure.

Source: Arthritis Research & Therapy

DOI: 10.1186/s13075-025-03686-6