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.

Keywords: Ulcerative colitis; cardiovascular risk; inflammatory bowel disease.

Graphical Abstract

Figure 1.

Proportion of patients in the tofacitinib UC OCTAVE clinical programme in each baseline 10-year CV risk category. Percentages do not add up to 100%, as ASCVD risk scores were not calculated in 48 patients due to one or more components of the ASCVD-PCE being missing, and also because remaining percentages were rounded to whole numbers. Prior ASCVD was defined as a history of any of coronary artery disease [including myocardial infarction], cerebrovascular disease [including stroke], or peripheral artery disease. Patients without prior ASCVD were categorised according to their 10-year ASCVD risk at baseline, per the ASCVD-PCE calculator, as recommended by the American College of Cardiology. Baseline was defined as first tofacitinib exposure. Includes data from the Phase 2 induction study [NCT00787202], the Phase 3 studies (OCTAVE Induction 1 and 2 [NCT01465763; NCT01458951] and OCTAVE Sustain [NCT01458574]), and the open-label, long-term extension study (OCTAVE Open [NCT01470612]), from patients who received ≥1 dose of tofacitinib 5 mg or 10 mg BID [N = 1157]. ASCVD, atherosclerotic CV disease; ASCVD-PCE, ASCVD pooled cohort equation[s]; BID, twice daily; CV, cardiovascular; N, total number of patients included in the analysis; n, number of patients in each category; UC, ulcerative colitis.

Figure 2.

IRs of MACE in the tofacitinib UC OCTAVE clinical programme, stratified by baseline 10-year CV risk category. MACE were adjudicated by an independent review committee and defined as any of myocardial infarction, stroke, or CV death. Events that occurred >28 days after the last dose of study drug were excluded. Prior ASCVD was defined as a history of any of coronary artery disease [including myocardial infarction], cerebrovascular disease [including stroke], or peripheral artery disease. Patients without prior ASCVD were categorised according to their 10-year ASCVD risk at baseline, per the ASCVD-PCE calculator, as recommended by the American College of Cardiology. Includes patients with prior ASCVD and patients for whom baseline CV risk could be determined, and excludes data from the Phase 2 study; therefore, N = 1124 for the assessment of adjudicated MACE. In addition, 47 patients were excluded due to one or more components of the ASCVD-PCE being missing. ^aUpper CI value continues beyond the axis shown [10.07]. ASCVD, atherosclerotic CV disease; ASCVD-PCE, ASCVD pooled cohort equation[s]; CI, confidence interval; CV, cardiovascular; IR, incidence rate [unique patients with events per 100 PY of exposure]; MACE, major adverse CV event[s]; N, number of patients with prior ASCVD or non-missing baseline ASCVD score; n, number of unique patients with a MACE; PY, patient-years; UC, ulcerative colitis.