C0362 - Major Cardiovascular Adverse Events by Baseline Cardiovascular Risk Stratification in Patients With Ulcerative Colitis Treated With Tofacitinib: Data From the OCTAVE Clinical Program

Introduction: Tofacitinib is an oral small molecule JAK inhibitor for the treatment of UC. Results from ORAL Surveillance, a post-authorization safety study in patients (pts) with RA aged ≥ 50 years with ≥ 1 additional cardiovascular (CV) risk factor indicated increased risk of major adverse CV events (MACE) and malignancies (excluding NMSC) with tofacitinib vs tumor necrosis factor inhibitors. Pts with IBD are at increased risk of atherosclerotic CV disease (ASCVD; coronary artery disease, cerebrovascular disease, or peripheral artery disease) vs the general population. The ASCVD-pooled cohort equations calculator, a validated risk-prediction tool recommended by the ACC, considers traditional CV risk factors to estimate 10-year risk of primary ASCVD. This study evaluated MACE occurrence stratified by baseline CV risk in the tofacitinib OCTAVE clinical program.

Methods: 1,157 pts (median treatment duration 623 [range 1–2,850] days; 2,814.4 pt-years [PY] of exposure) who received tofacitinib 5 or 10 mg BID in a Phase(P)2 induction study (NCT00787202) and P3 studies (OCTAVE Induction 1&2 [NCT01465763; NCT01458951], OCTAVE Sustain [NCT01458574], and OCTAVE Open [NCT01470612]) were included. Proportions and incidence rates (IRs; unique pts with events / 100 PY of exposure) were evaluated for MACE. MACE IRs were stratified by baseline (first tofacitinib exposure) CV risk profile: first by history of ASCVD (HxASCVD), then pts without HxASCVD were categorized by 10-year ASCVD risk.

Results: Of 1,109 pts in which baseline CV risk was assessed, 4% had a HxASCVD, and most (87%) pts without a HxASCVD had a low / borderline risk of ASCVD (Figure). 8 pts had an adjudicated MACE; 1 event occurred in a pt with a HxASCVD, 5 in pts in intermediate / high ASCVD risk categories, and 2 in pts in the low ASCVD risk category. MACE IR in pts with a HxASCVD was 0.95 (0.02, 5.27) and IRs in pts without a HxASCVD by ASCVD risk were: high 1.81 (0.05, 10.07); intermediate 1.54 (0.42, 3.95); borderline 0.00 (0.00, 2.85); and low 0.09 (0.01, 0.32). 7 pts with MACE had a medical history of CV risk factors, and 7 were receiving statins (Table).

Discussion: In the tofacitinib OCTAVE clinical program, MACE were infrequent. Most pts had a low baseline ASCVD risk. This analysis highlights a potential association between baseline CV risk and MACE incidence in pts with UC treated with tofacitinib. Interpretation of these data was limited by the low number of events and short median treatment duration vs assessment of long-latency events.