P616 Prescribing practices of tofacitinib and preferences amongst high-risk patients in the UK

Abstract

Abstract Background Tofacitinib was licensed for use in patients with ulcerative colitis in August 2018. Because it is administered orally, has a rapid onset of action and is relatively inexpensive, it was quickly adopted in real-world practice. Safety warnings linking high-dose tofacitinib use to venous thromboembolic events (VTE) and death followed. Further warnings were issued linking its use to an increased risk of malignancy and adverse cardiovascular events in patients: over 65 years, with a history of diabetes, current or past smokers, and those with a history of coronary vascular disease. The most recent Medicines and Healthcare products Regulatory Agency (MHRA) statement advised against the use of all commercially available JAKi in this high-risk cohort unless a suitable alternative is unavailable (MHRA 2023). We sought to define the number of patients who had, or were, being treated with tofacitinib who were in this high-risk group and the proportion who opted to switch therapy once we had outlined their risk-status and the MHRA advice to them. Methods We conducted a retrospective observational cohort study of 131 patients with UC and IBD-U (61% male [80/131]; median age 43 years [range 16-85]; 46% [60/131] patients had previously had at least one biologic agent) treated with tofacitinib from October 2018 to December 2022 in our centre with at least 3 months follow-up. Patients were categorised as high-risk according to the MHRA statement if they had at least one of the criteria above. Results Overall, about one-third, 31.3% [41/131] patients that we had treated with tofacitinib were classified in the MHRA high-risk group. Rates of treatment discontinuation were similar in the high-risk versus no risk group. In the high-risk group ten patients (24.4% [10/41]) had discontinued treatment due to lack of response (4) or an adverse event (6). The most common adverse events were herpes zoster infections (14.6%), malignancy (3.3%) and infections requiring hospitalisation (3.3%). Two patients died while on treatment (one due to complications following cervical spinal surgery and the other due to ischaemic heart disease). There were no incidences of VTE. We clinically reviewed 29 high risk patients who were being treated with tofacitinib after a median of 2.4 years (range 0.6-4.56) of treatment. 25/29 high-risk patients decided on continuing their treatment in spite of the health care warnings and alternative therapies being available. Conclusion About one-third of our tofacitinib-treated patients were classified as at high-risk. The majority of high-risk patients opted to continue therapy even though alternative therapies were available.