5PSQ-085 Safety assessment of Janus kinase inhibitors in clinical practice

Background and Importance Janus kinase inhibitors (JAKi) tofacitinib, baricitinib, upadacitinib and filgotinib are immunosuppressants indicated for the treatment of chronic inflammatory disorders. Concern regarding their safety has recently arisen since publication of new data in recent years. Aim and Objectives To assess the safety of tofacitinib, baricitinib, upadacitinib and filgotinib for the treatment of chronic inflammatory disorders in real clinical practice. To compare it with the clinical trials (CT) results. Material and Methods Observational restrospective study including all patients treated with JAKi from January 2019 to August 2023 in a tertiary hospital. Data were obtained by review of electronic medical records and laboratory database. Variables studied were: patient demographics, prescribing units, adverse reactions(AR), treatment duration and motive of interruption. Results 271 (74,5% women) patients were included in this study, with a median age of 55 (18–92) years. 243 had rheumatology disorders, 21 digestive disorders, 3 dermatology disorders and 4 both rheumatology and digestive disorders. 122(45%) patients suffered some kind of toxicity during treatment with JAKi. The most frequently registered AR by drug are shown in the table 1: In 43 (15.9%) patients treatment was stopped due to toxicity (16 baricitinib, 19 tofacitinib, two upadacitinib, one filgotinib). The most frequent AR that led to interruption were gastrointestinal disorders with tofacitinib and infections with baricitinib. Treatment had to be stopped in five patients because of neoplasm diagnosis (three baricitinib, two tofacitinib). Two patients died during period of study (one tofacitinib, one baricitinib). Dose reduction because of toxicity was required in one patient treated with tofacitinib and in 12 treated with baricitinib. Conclusion and Relevance In general terms, for tofacitinib and baricitinib, our study carried out in real-world clinical practice shows a toxicity profile similar to the one described in CT. All AR are described in the literature. Infections and hypercholesterolaemia are among the most frequent AR in our study and in CT. Although most of the AR were tolerable, there were several cases of severe AR led to treatment interruption. In contrast to recent CT results, no major adverse cardiovascular events were registered in our study. A bigger sample is needed to make conclusions about upadacitinib and filgotinib safety. References and/or Acknowledgements Conflict of Interest No conflict of interest.