Background/Purpose: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA) are chronic inflammatory arthritis (CIAs). Janus kinase inhibitors (JAKis) have emerged as a promising therapeutic option for managing these conditions. However, their safety profile remains under ongoing investigation due to adverse events (AEs) reported in clinical trials and real-world data. This study aimed to evaluate the safety of JAKis in patients with CIA in a real-life setting.

Methods: A retrospective observational study was conducted on patients diagnosed with RA, PsA, or SpA who received treatment with JAKis—baricitinib (BAR), tofacitinib (TOF), upadacitinib (UPA), or filgotinib (FIL)—between 2017 and 2024. The primary outcome was the incidence and causes of treatment discontinuation due to AEs. Clinical, sociodemographic, and treatment-related variables were analyzed. Incidence rates (IR) were calculated per 100 patient-years using survival analysis techniques, along with 95% confidence intervals (CI).

Results: A total of 181 patients were included (83.4% female; mean age: 56.2 ± 12.7 years). The most common comorbidities were dyslipidemia (43%), hypertension, and thyroid disorders; 8.3% had cardiovascular disease. A total of 227 JAKi treatment courses were recorded: BAR (41.8%), TOF (15.8%), UPA (37.5%), and FIL (4.8%). Treatment was discontinued due to AEs in 49 courses among 42 patients (23%). Respiratory infections were the leading cause (36.7%), followed by general malaise (28.5%). Ten AEs were classified as serious (e.g., diverticulitis, pneumonia requiring hospitalization, gastric cancer, and pulmonary embolism), including three deaths (two due to COVID-19 pneumonia and one due to gastric cancer). The overall IR for AE-related discontinuation was 14.74 per 100 patient-years (95% CI: 11.14–19.51), with 50% of cases occurring within the first 1.65 years of therapy. Discontinuation rates were higher among women and patients with cardiovascular disease. Compared to TOF (IR: 21.8; 95% CI: 11.7–40.5), BAR and UPA/FIL showed lower discontinuation rates (IR for UPA/FIL: 13.6; 95% CI: 8.0–21.3; IR for BAR: 13.03; 95% CI: 9.3–21.1).Multivariate analysis identified cardiovascular disease as a significant predictor of AE-related discontinuation (HR: 4.07; 95% CI: 2.17–7.63; p< 0.001). No significant differences were found based on sex, age, or specific JAKi agent.

Conclusion: JAK inhibitors showed an overall acceptable safety profile in patients with chronic inflammatory arthritis. Cardiovascular comorbidity was the most relevant risk factor associated with AE-related discontinuation, independent of JAKi type or patient demographic characteristics.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-of-jak-inhibitors-jaki-in-chronic-inflammatory-arthritis-cia-an-observational-study/