THE EFFECT OF TOFACITINIB ON SERUM LIPIDS AND CARDIOVASCULAR SAFETY IN PATIENTS WITH ULCERATIVE COLITIS - RESULTS FROM THE TOFACITINIB ULCERATIVE COLITIS CLINICAL PROGRAM

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). We describe baseline cardiovascular (CV) risk, the effect of tofacitinib treatment on lipid concentrations, and incidence rates (IRs; patients with events per 100 patient-years) of major adverse CV events (MACE) in patients enrolled in the UC global development program. Methods: Analyses were performed for patients in 3 placebo-controlled induction studies (Ind), a 52-week placebo-controlled maintenance study, and an ongoing, open-label, long-term extension study (N=1157). Lipid concentrations were assessed at pre-induction baseline and up to Week 61 for responders to tofacitinib 10 mg twice daily (BID) in Ind who were randomized to tofacitinib 5 or 10 mg BID or placebo in Main. IRs and confidence intervals (CI) for MACE were calculated (follow-up to December 2016), including patients with ≥1 event per 100 patient-years of exposure. The distribution of CV risk factors and Reynolds Risk Score was determined for male patients ≤45 years and >45 years, and female patients ≤55 years and >55 years. Results: Mean patient age was 41.3 years. At baseline, Reynolds Risk Score was ≥10% in 24.4% of males >45 years and 6.4% of females >55 years. Most patients did not require lipid-lowering medication (Table). Dose-dependent increases in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides were observed, which remained stable up to Week 61 in Main patients assigned to placebo, tofacitinib 5 mg BID and 10 mg BID; LDL-c: HDL-c and TC.: HDL-c ratios were unchanged. In the overall clinical program, 4 MACE events were reported (IR 0.24; 95% CI 0.07, 0.62; males 3/668 [0.4%]; females 1/475 [0.2%]): 1 hemorrhagic stroke, 1 aortic dissection, 1 acute coronary syndrome, and 1 myocardial infarction. The aortic dissection resulted in death (patient had 1 CV risk factor). The hemorrhagic stroke led to permanent tofacitinib discontinuation. The myocardial infarction and acute coronary syndrome events led to temporary tofacitinib discontinuation (patients completed the study). These 3 patients had ≥4 CV risk factors at baseline, including hyperlipidemia. Conclusion: Tofacitinib treatment was associated with increases in TC, HDL-c, and LDL-c in patients with UC, while LDL-c: HDL-c and TC.: HDL-c ratios were unaffected. These results are similar to those reported for rheumatoid arthritis. MACE events were infrequent, with rates similar to those reported in the tofacitinib rheumatoid arthritis program and for other UC agents; 3 of 4 patients had multiple CV risk factors. [Table Presented]