Background and Importance Tofacitinib, baricitinib, upadacitinib and filgotinib are Janus kinase inhibitors (IJAKs) indicated in rheumatoid arthritis (RA). The EMA notified that in patients with RA who were ≥50 years with at least one cardiovascular risk factor had an increased risk of major adverse cardiovascular events (MACE), and malignancies with use of tofacitinib relative to TNF-alpha inhibitor: https://www.ema.europa.eu/en/documents/dhpc/direct-healthcare-professional-communication-dhpc-xeljanz-tofacitinib-increased-risk-major-adverse_en.pdf
Although it is being evaluated, it is still unknown if this risk is shared by other IJAKs.
Aim and Objectives To describe and compare the safety of tofacitinib, baricitinib, upadacitinib and filgotinib in patients with RA in a real-world-setting.
Secondary objective to analyse if there is a relationship between MACE and malignancies with a patient profile with a higher risk of developing them as established in the alert.
Material and Methods Retrospective/prospective observational study of RA patients under treatment with tofacitinib, baricitinib, upadacitinib and filgotinib until September 2022.
Safety was determined based on the adverse events (AEs) reported.
Variables sex, age at start,time-of-treatment, reason for discontinuation, risk factor´s MACE, risk factors for malignancies, and AEs.
Statistical analysis a description of characteristics and events that occurred in the cohort was carried out. Associations were later explored.
Results 124 patients (80.6% women) were enrolled. Mean age: 55.8 (SD11.8) years.
Treatments received tofacitinib (n=60), upadacitinib (n=49), baricitinib (n=21) and filgotinib (n=14), because 19 patients (15.3%) were treated with more than one IJAKsequentially.
Median of treatment; tofacitinib: 399 (171-884) days, baricitinib: 308 (210-632), upadacitinib: 287 (130-477) and 93 (60-171) for filgotinib.
We identified 110 patient treatments with an increased risk of MACE or malignances.
AEs were reported in 39 (31,5%) treatments (21, 9, 7, and 2 cases with tofacitinib, upadacitinib, baricitinib and filgotinib) being the most common herpes zoster. Only 2 patients suffered a MACE in the total cohort (both with tofacitinib).
There were 79 end-of-treatment because of inefficacy (n=46), AE (n=22), both (n=7) or for being considered a risk patient (n=4).
No association could be established between risk patient and the development of adverse events, neither minor or major.
Conclusion and Relevance Therefore, it is still unknown if the exchange strategy between them is adequate to reduce the risk. Limitation: a larger sample size and longer follow-up time are required to detect major AEs and their association with patients at risk.
Conflict of Interest No conflict of interest