A8.5 Baricitinib effects on serum cholesterol and circulating lipid particles in a phase 2B study in patients with rheumatoid arthritis

Abstract

Background Baricitinib, a novel oral JAK1/2-inhibitor, was evaluated in a Phase 2b study in patients with moderate-to-severe RA. The primary ACR20 12-week-endpoint was met, and maintained through 24 weeks. 1 Objective To evaluate changes in serum LDL, HDL, and total cholesterol over 24 weeks of baricitinib treatment compared with placebo. Methods Patients were randomised to QD dosing with placebo (n = 98) or 1, 2, 4, or 8 mg of baricitinib with ˜50 patients per treatment arm. Serum lipids were determined at screening, baseline and at Weeks 2, 4, 8, 12, 14, 16, 20, 24, and particle size and number were determined by Nuclear Magnetic Resonance (NMR) at baseline, Weeks 12/24. Results Baricitinib treatment resulted in dose- and time-dependent increase relative to placebo in LDL, HDL and total cholesterol detectable by Week-2. The mean percent increase in total cholesterol in the combined baricitinib arms was 9.5% (p Conclusions The increase in LDL-cholesterol with baricitinib treatment is attributed to a shift towards larger particles rather than an overall increase in LDL-particle number at Week-12 and persisting through 24 weeks, while changes observed in HDL-cholesterol were associated with an increase in total number of HDL-particles. 1 Reference Genovese MC, Keystone E, Taylor P, et al . Arthritis Rheum 2012; 64 :2487.