P676 Correlation of lipid levels with reduction in inflammation in patients with ulcerative colitis: Data from the tofacitinib OCTAVE clinical trials

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Mild lipid elevations-with no evidence suggesting correlation with major cardiovascular events-have been seen in tofacitinib-treated patients (patients).1,2 We evaluated relationships between inflammatory status and lipid levels in tofacitinib-treated patients with UC. Methods: This analysis included patients from two randomised, placebo-controlled tofacitinib induction trials in patients with moderate-to-severe UC (OCTAVE Induction 1 and 2, NCT01465763 and NCT01458951). Correlation of Week 8 changes from baseline in lipid parameters (low-and high-density lipoprotein cholesterol [LDL; HDL], and total cholesterol [TC]) with Week 8 changes from baseline in C-reactive protein (CRP), and with the proportions of patients with mucosal healing (Mayo endoscopic subscore ≤1) and remission (total Mayo score ≤2, no individual subscore >1 and rectal bleeding subscore = 0) at Week 8, were determined. Results: In OCTAVE Induction 1 and 2, 234 patients received placebo and 905 received tofacitinib 10 mg twice daily (BID). Consistent with previously reported data,2 there were greater increases from baseline in lipid levels, decreases from baseline in CRP, and greater rates of mucosal healing and remission at Week 8 with tofacitinib 10 mg BID vs. placebo (Table). The Pearson correlation coefficients at Week 8 between CRP and LDL, HDL and TC levels were significantly different from zero for both placebo-treated (LDL:-0.23; HDL:-0.34; TC:-0.36) and tofacitinib-treated patients (LDL:-0.19; HDL:-0.25; TC:-0.27). For tofacitinib-treated patients, correlation coefficients at Week 8 between mucosal healing and HDL (0.12) and TC (0.09), and between remission and HDL (0.08), were significantly different from zero. Conclusions: There was significant negative but small correlation between lipid and CRP changes in the tofacitinib and placebo groups. These data suggest that lipid changes seen in patients treated with tofacitinib may be partially due to the beneficial effect of reduced inflammation. More studies are warranted to better understand these correlations.