P567 Safety analysis of tofacitinib in ulcerative colitis: Real-world outcomes from a three-year UK observational cohort study
Honap, S.(1,2);Sharma, E.(1);Ray, S.(1);Mawdsley, J.(1);Anderson, S.(1);Samaan, M.(1);Pavlidis, P.(1,2);Irving, P.(1);
(1)Guy’s and St Thomas’ NHS Foundation Trust, IBD Centre - Department of Gastroenterology, London, United Kingdom;(2)King's College London, School of Immunology and Microbial Sciences, London, United Kingdom;
Serious adverse events (SAE), including venous thromboembolism (VTE) and major adverse cardiovascular events (MACE), have been reported in tofacitinib post-marketing trials. However, safety data extending beyond six months in the real world are scarce.1 We explored the incidence rates (IR) of adverse events (AE) in a tofacitinib-treated cohort of ulcerative colitis (UC) patients at a large tertiary centre over three years.
We conducted a retrospective analysis of a prospectively maintained database of consecutive patients commencing tofacitinib from October 2018 to October 2021. AE details were extracted from elective and emergency visits during induction and maintenance treatment. SAEs were defined as AEs that were life-threatening or required hospitalisation. We also assessed changes in haematological and biochemical parameters, including lipid levels, during treatment. Exact Poisson confidence intervals (CI) (adjusted for PYs) were calculated to determine IRs and univariate analyses and multivariate logistic regression were performed to examine AE risk factors.
A total of 103 patients were studied with a median follow up duration of 53 weeks (range 1-156). Median treatment duration on 10mg bd was 18 weeks (range 1-135). AEs and SAEs were recorded in 37% and 16% of the study cohort, respectively, over 118 PYs exposure. Infection was the most common AE and hospitalisation for disease progression requiring colectomy while on tofacitinib was the most frequent SAE (table 1). Overall, the IR for SAEs was 13.6 per 100 PYs (95% CI 9.1-26.0) (table 2). Single dermatomal herpes zoster (HZ) reactivation (including one case of HZ opthalmicus) occurred in 5%; all occurred on 10mg BD dosing, and all were successfully treated with antiviral therapy. Duration of high dose tofacitinib treatment, age, weight, concomitant corticosteroid use, and prior TNF exposure were not associated with AEs. Although there was a significant increase in total cholesterol (TC) and low-density lipoproteins, the TC to high-density lipoprotein ratio remained unchanged (table 3) and no patient required the introduction of a lipid lowering agent. Tofacitinib was well tolerated and excepting treatment discontinuation due to drug failure requiring surgery, AEs resulted in tofacitinib withdrawal in only one patient (headaches). There were no cases of MACE or VTE.
Although a third of our cohort had AEs, tofacitinib-treatment failure and subsequent hospitalisation and surgery was the most frequently occurring. No new safety signals were identified with extended real-world follow up.
1. Taxonera C et al. Real-World Effectiveness and Safety of Tofacitinib in Patients With UC: Systematic Review and Meta-Analysis. Inflamm Bowel Dis. 2021