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

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). In the tofacitinib UC clinical program, the majority of patients did not have cardiovascular risk factors at baseline, and increases in lipid levels occurred primarily during induction and remained elevated to Week 61 during maintenance; lipid ratios were relatively unchanged.1 Here, we present updated results of lipid levels in the ongoing, open-label, long-term extension (OLE) study (NCT01470612) and major adverse cardiovascular events (MACE) in the Phase 3/OLE tofacitinib UC clinical program. Methods: Lipid levels were assessed at multiple time points, and changes from OLE study baseline to Month 48 in the OLE study were evaluated. Lipid-lowering agent (LLA) use (proportion of patients) and adjudicated MACE (proportion of patients and incidence rate [IR; unique patients with events per 100 patient-years] with 95% confidence interval [CI]) were reported in patients with UC in two Phase 3, 8-week, placebo-controlled induction studies (OCTAVE Induction 1&2; NCT01465763, NCT01458951), a Phase 3, 52-week, placebo-controlled maintenance study (OCTAVE Sustain; NCT01458574), and the OLE study (data as of May 2019; database not locked). Results: No major changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides, LDL-c:HDL-c, and TC.:HDL-c from OLE study baseline were observed at Month 48 of the OLE study (Table). In the Phase 3/OLE program (N=1,124), 7.7% of patients had a new LLA added and 1.9% of patients had their LLA dose increased. Seven MACE were reported (IR 0.26; 95% CI 0.11, 0.54; 2,654.66 patient-years); the IR has remained stable since December 2016 (IR 0.24; 95% CI 0.07, 0.62).1 Reported MACE were one each of myocardial infarction, acute myocardial infarction, acute coronary syndrome, cerebrovascular accident, hemorrhagic stroke, cerebellar hemorrhage, and aortic dissection. Both myocardial infarction events and the acute coronary syndrome event led to temporary tofacitinib discontinuation; the hemorrhagic stroke, cerebrovascular accident, and cerebellar hemorrhage led to permanent tofacitinib discontinuation; and the aortic dissection resulted in death. Of the seven patients with MACE, five had cardiovascular risk factors at baseline. Conclusion: At Month 48 of the OLE study, lipid levels and ratios remained generally unchanged from OLE study baseline following tofacitinib treatment. MACE were infrequent, with the IR remaining stable since the previous report.1 Limitations include low patient numbers and short tofacitinib exposure duration. Longer-term observation studies will further assess risk. Reference: 1. Sands BE et al. Clin Gastroenterol Hepatol 2019;Epub ahead of print