P562 Safety and persistence oh the first JAK inhibitor Tofacitinib in patients with ulcerative colitis

Abstract

Abstract Background A drug safety warning was published in 2021 about the risks associated with tofacitinib, which were found in the Oral-Surveillance study. The European Medicines Agency (EMA) and the Spanish Agency for Medicines and Medical Products (AEMPS) have recommended, due to this warning, some precautions in the prescriptions: It should not be used in patients older than 65 years of age, people who are current or past smokers, or individuals with cardiovascular or malignancy risk factors unless there are no suitable treatment alternatives. The aim fo this study was to assess the safety and treatment persistence of tofacitinib in clinical practice in three Spanish third-level hospitals. Methods Retrospective observational multicenter study of patients with Ulcerative Colitis (UC) treated with tofacitinib from January 2019 to October 2023. Sex, age, line of treatment, persistence, adverse events, discontinuations and risk factors associated with the warning were evaluated. Information was collected from the hospital’s information systems. Results A total of 56 patients, 53% women, mean age 55 (18-72) years old. Tofacitinib was the first line treatment in 2% of the patients after loss of response to the conventional treatment, second line for 57%, third line for 30% and fourth line for 11% after biological drugs (infliximab, adalimumab, vedolizumab and ustekinumab). 52% of patients needed maintenance with the higher doses (10mg dose) after induction due to the lack of response with the 5 mg dose, with an average of 52 weeks. The mean persistence was 18 months (1-56), with 19,6% discontinuations due to primary failure and secondary failure. It must be noted that one patient, who received tofacitinib for three years, underwent appendicular neoplasia and finally died due to liver metastases. There was not discontinuation due to other adverse events, which were: 3,6% herpes zoster, 46,4% increased total cholesterol level >200 mg/dl (compared with the initial measurement), of which 19% received statins.There were 27 (48%) patients with risk factors associated with the safety warning: 37% cardiovascular risk, 3,7% older than 65 years, 11,1% previous malignancy, 18,5% current or past smokers and 29,6% had several of these risks. Conclusion In this multicenter real-world treatment-refractory UC population cohort, tofacitinib was well tolerated in the long term, even in the patients with risk factors related to the warning.