BARICITINIB EFFECTS ON LIPID AND NMR-MEASURED LIPOPROTEIN PROFILES IN A PHASE 3 STUDY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Baricitinib (bari), a JAK1 and JAK2 inhibitor, was efficacious compared to placebo (PBO) and adalimumab (ADA) in a 52-week (Wk) Ph 3 study in patients (pts) with active rheumatoid arthritis (RA) and an inadequate response (IR) to methotrexate (MTX). Objectives: To evaluate changes in lipid and lipoprotein profile over 52 wks of treatment with bari or ADA compared with PBO in the aforesaid study. Methods: MTX-IR pts with active RA were randomized 3:3:2 to bari 4mg once daily (QD), PBO, or ADA 40mg biweekly. Lipid profile was evaluated at baseline and at Wks 12, 24, and 52 and nuclear magnetic resonance (NMR)-measured lipoprotein particle size and number at baseline and Wk 12. Results: Treatment with both bari and ADA resulted in significant mean increases from baseline to Wk 12 in total cholesterol (PBO -0.2%, bari 15%, ADA 7%), triglycerides (PBO 1%, bari 17%, ADA 12%), LDL-C (PBO -0.6%, bari 16%, ADA 9%), and HDL-C (PBO 0.8%, bari 17%, ADA 8%). These increases persisted through Wk 52. The NMR lipoprotein profile revealed similar changes for bari and ADA relative to PBO regarding an increase in large LDL, a decrease of all types of small LDL, and increases in IDL, VLDL and subfractions, and total HDL as well as large and small HDL particles (Table 1). Significant increases in total LDL particle numbers were not observed with either bari or ADA. NMR analyses (mean change from baseline ± SD) Wk 12 PBO (N=488)Bari (N=487)ADA (N=330) Total LDL particles−22.4±236.115.0±282.3−33.9±257.4* Large LDL particles−2.8±158.081.9±191.7***42.2±182.2*** Small LDL particles−21.3±285.8−81.0±327.3***−82.7±349.7*** Medium small LDL particles−2.9±60.2−16.6±67.6***−15.5±74.4*** Very Small LDL particles−18.5±228.7−64.4±263.0***−67.2±278.6*** Total HDL particles−0.03±4.24.8±5.3***2.0±4.6*** Large HDL particles0.0±2.21.0±2.7***0.4±2.2** Medium HDL particles0.1±2.80.7±3.5***−0.4±3.1 Small HDL particles−0.2±4.13.1±5.2***2.0±4.3*** IDL particles1.7±38.614.0±48.5***6.6±40.4* Total VLDL particles−1.7±24.712.0±28.8***6.1±23.8*** Large VLDL particles−0.1±2.91.0±3.3***0.5±2.7** Medium VLDL particles−0.8±15.75.5±18.2***3.2±13.7*** Small VLDL particles−0.8±15.05.6±17.1***2.3±17.2* Values for LDL and VLDL particles are nmol/L; Values for HDL particles are μmol/L; Within-treatment p-values, *p≤0.05, **p≤0.01, ***p≤0.001. Conclusions: The increase in LDL-C and HDL-C with both bari and ADA is accompanied by an increase in large LDL, total HDL particles and a decrease in small LDL. The nature of these changes may potentially indicate a more atheroprotective profile than that of the PBO group. References: 1. Taylor et al. Arthritis Rheumatol 2015;67(suppl10). Abstract 2L. Disclosure of Interest: P. Taylor Grant/research support from: UCB, GlaxoSmithKline, Celgene, Consultant for: UCB, Eli Lilly & Company, Pfizer, Galapagos, Merck, GSK, AbbVie, Takeda, BMS, E. Keystone Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, F. Hoffman-La Roche Inc, Janssen, Eli Lilly & Company, Novartis, Pfizer, Sanofi-Aventis, Consultant for: Abbott, AstraZeneca, Biotest, BMS, F. Hoffmann-La Roche, Genentech, Janssen, Eli Lilly & Company, Merck, Pfizer, UCB, Speakers bureau: Abbott, Amgen, AstraZeneca, BMS Canada, F. Hoffmann-La Roche, Janssen, Pfizer, UCB, Y. Tanaka Grant/research support from: Mistubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, Bristol-Myers, Speakers bureau: Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Santen, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Celgene, Daiichi, Eli Lilly & Company, Galapagos, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, Employee of: Director Imaging Rheumatology BV, J. Zhong Employee of: Quintiles Transnational, Inc, S. Thanabalasundrum Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, G. Ruotolo Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, D. Schlichting Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Rooney Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, W. Macias Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Zuckerman Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. de Bono Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, M. Weinblatt Grant/research support from: Crescendo Bioscience, Consultant for: Eli Lilly & Company, Crescendo Bioscience, Pfizer, AbbVie DOI: 10.1136/annrheumdis-2016-eular.1595Citation: Annals of the Rheumatic Diseases, volume 75, supplement 2, year 2016, page 257Session: Rheumatoid arthritis - non-biologic treatment and small molecules (Poster Presentations )