Major Adverse Cardiovascular Events by Baseline Cardiovascular Risk in Patients with Ulcerative Colitis Treated with Tofacitinib: Data from the OCTAVE Clinical Programme

Abstract Background and Aims Patients with inflammatory bowel disease have increased risk of atherosclerotic cardiovascular [CV] disease [ASCVD]. Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis [UC]. We report major adverse CV events [MACE] in the UC OCTAVE programme, stratified by baseline CV risk. Methods Rates of MACE were analysed by baseline [first tofacitinib exposure] CV risk profile: prior ASCVD, or 10-year ASCVD risk categories [low, borderline, intermediate, high]. Results Of 1157 patients [2814.4 patient-years of exposure; ≤7.8 years’ tofacitinib treatment], 4% had prior ASCVD and 83% had no prior ASCVD and low–borderline baseline 10-year ASCVD risk. Eight [0.7%] patients developed MACE; one had prior ASCVD. Incidence rates [unique patients with events/100 patient-years of exposure; 95% confidence intervals] for MACE were: 0.95 [0.02–5.27] in patients with prior ASCVD; and 1.81 [0.05–10.07], 1.54 [0.42–3.95], 0.00 [0.00–2.85], and 0.09 [0.01–0.32] in patients without prior ASCVD and with high, intermediate, ­borderline, and low baseline 10-year ASCVD risk, respectively. For the 5/7 patients with MACE and without prior ASCVD, 10-year ASCVD risk scores were numerically higher [>1%] prior to MACE versus at baseline, primarily due to increasing age. Conclusions Most patients receiving tofacitinib in the UC OCTAVE programme had low baseline 10-year ASCVD risk. MACE were more frequent in patients with prior ASCVD and higher baseline CV risk. This analysis demonstrates potential associations between baseline CV risk and MACE in patients with UC, suggesting CV risk should be assessed individually in clinical practice. ClinicalTrials.gov NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612. Graphical Abstract Graphical Abstract