Serious infection risk of tofacitinib in RA
Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care
SUMMARY:
Recently, serious infections related to the use of tofacitinib (TOF) for treatment of rheumatoid arthritis (RA) have raised considerable interest. This study aimed to compare the risk for serious infections in patients with RA upon receiving TOF versus alternative biologic disease-modifying antirheumatic drugs (bDMARDs) by age at treatment initiation. The authors, led by GCIR member Prof. Axel Finckh, identified adult RA patients exposed to TOF or bDMARDs using data collected by the Swiss registry for inflammatory rheumatic diseases (SCQM) from 2015 to 2018. The event of interest was the first serious infection (SI) during drug exposure. The ratio of SI hazards (HR) of TOF versus bDMARDs was estimated as a function of age using covariate-adjusted Cox regression. A total of 1687 patients provided time at risk for a first SI during study participation and drug exposure for 2238 different treatment courses, 345 for TOF and 1893 for bDMARDs. They identified first SIs (12/12 on TOF versus 32/31 on bDMARDs). For patients aged ≥ 69 years, the treatment HR started to be increased (lower limit of 95% confidence intervals (LLCIs) > 1). By the age of 76, the difference between TOF and bDMARDs started to be clinically relevant (LLCIs > 1.25). Their results suggest that one should expect an increased risk for SIs in older patients treated with TOF compared to bDMARDs supporting a cautious use of TOF in these patients.
Link to full article published by Scientific Reports: https://www.nature.com/articles/s41598-023-44841-w
Why is it important?
Rheumatoid arthritis (RA) is an autoimmune disease that causes joint destruction and extra-articular manifestations. Disease-modifying antirheumatic drugs (DMARDs) stop or slow down the disease process in inflammatory types of arthritis. They have dramatically improved RA care with unprecedented efficacy in both relieving symptoms and preventing joint damage. In August 2013, tofacitinib (TOF) was introduced and quickly embraced by the rheumatology community in Switzerland for its efficacy and convenience. The EULAR 2020 guidelines suggest considering JAK inhibitors, including TOF, as second-line treatment for patients with moderate to high disease activity who do not respond to methotrexate monotherapy, alongside TNF inhibitors and non-TNF biologics.
Because DMARDs suppress the immune system to control inflammation, they all increase the risk of infection, and these bacterial, viral or opportunistic infections are a major concern for RA patients. However, the relative risks and types of serious infection may vary between DMARDs due to their different modes of action. Because of a recent trial suggested an increased risk of SI and other adverse events with TOF compared to anti-TNF agents, Professor Axel Finckh and his team conducted this study comparing the risks of serious infection (SI) in RA patients with different alternative antirheumatic agents.
Using data from the Swiss register of inflammatory rheumatic diseases, their analysis focused on age and use of TOFs compared to other biologic DMARDs. Their results confirmed an increased risk of SI in older patients (≥ 69 years) on treatment with TOF compared to biologic DMARDs. In fact, the study supports current recommendations to use TOF with caution in patients aged 65 years and older.
31 Oct 2023