Correlation of Lipid Levels with Reduction in Inflammation in Patients with Ulcerative Colitis: Data from the Tofacitinib Octave Clinical Trials

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.1,2 We evaluated relationships between inflammatory status and lipid levels in tofacitinib-treated patients with UC. Methods: This analysis included patients from two randomized, placebo-controlled tofacitinib induction trials in patients with moderate to severe UC (OCTAVE Induction 1 & 2, NCT01465763 & NCT01458951). Correlation of Week 8 changes from baseline in lipid parameters (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol) with Week 8 changes from baseline in C-reactive protein, 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 & 2, 234 patients received placebo and 905 patients 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 C-reactive protein, 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 C-reactive protein and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol levels were significantly different from zero for both placebo-treated patients (low-density lipoprotein cholesterol: -0.23; high-density lipoprotein cholesterol: -0.34; total cholesterol: -0.36) and tofacitinib-treated patients (low-density lipoprotein cholesterol: -0.19; high-density lipoprotein cholesterol: -0.25; total cholesterol: -0.27). For tofacitinib-treated patients, correlation coefficients at Week 8 between mucosal healing and high-density lipoprotein cholesterol (0.12) and total cholesterol (0.09), and between remission and high-density lipoprotein cholesterol (0.08), were significantly different from zero. Conclusion: There was significant negative but small correlation between lipid and C-reactive protein 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. References: 1. Charles-Schoeman C et al. Semin Arthritis Rheum 2016;46:261-71. 2. Sandborn WJ et al. N Engl J Med 2017;376:1723-36. [Table Presented]