4CPS-175 Real-life safety in rheumatological patients treated with Janus kinase inhibitors: before and after an international safety warning

<h3>Background and Importance</h3> Despite the positive therapeutic impact of Janus kinase inhibitors (iJAKs) in the treatment of several immune-mediated inflammatory diseases, some concerns have been raised regarding their safety. In October 2022, EMA published measures to minimise the risk of serious adverse events (AEs) linked to their utilisation, including restrictions for their application among people ≥ 65 years, smokers and those at increased risk of major cardiovascular events and cancer. <h3>Aim and Objectives</h3> To identify the reason of treatment withdrawal in patients with rheumatoid diseases treated with any iJAK; describe the AE profile developed and analyse the impact on safety after the risk minimisation measures announcement. <h3>Material and Methods</h3> Retrospective, observational study that included all patients with rheumatoid diseases treated with iJAK at a university hospital since their first market launch in Spain (2018) to date. Data were extracted from the electronic medical record, and the patients‘ risk profile for developing AE was analysed according to the published safety signals. <h3>Results</h3> Among 160 patients included, 66,3% started the treatment before October 2022. To date, 51,3% (n=82) of the treatments have been withdrawn and the reasons were lack of effectiveness (63,4%, n=52), development of AE (28,1%, n=23) and others (8,5%, n=7). In this last group, three patients were considered at high-risk of AE according to issued safety measures so the iJAK was discontinued. The percentage of patients that discontinued treatment for safety reasons by active ingredient was: baricitinib (43,5%), upadacitinib (30,4%), filgotinib (17,4%) and tofacitinib (8,7%). Among the AEs, asthenia, herpes zoster, gastrointestinal disorders and headache were described as the most frequent; three serious AEs were identified: fatal pneumonia, deep venous thrombosis and prostate carcinoma. Major AEs, analysed before and after October 2022, showed that they occurred among patients &gt;65 and all the treatments were initiated before the safety warning announcement. <h3>Conclusion and Relevance</h3> A high percentage of drug withdrawals observed in patients treated with iJAK was due to ineffectiveness. The serious AE associated with iJAK application were related to the patient‘s risk profile. However, no serious AEs were described among patients who started with iJAK after the safety measures were issued, underlining the importance of an adequate selection of patients to start treatment with iJAK. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest