Article
Increases in Serum Cholesterol with Baricitinib Treatment are Associated with Favorable Changes in Apolipoprotein Content and with Improvement in DAS28-CRP in Patients with Rheumatoid Arthritis
Search Medline for
Authors
-
Joel M. Kremer
- Albany Medical College, The Center for Rheumatology, Albany, United States of America
-
Mark C. Genovese
- Stanford University School of Medicine, Palo Alto, United States of America
-
Ed Keystone
- The Rebecca MacDonald Centre For Arthritis & Autoimmune Diseases, Mount Sinai Hospital, 60 Murray St.,, Toronto, Ontario M5T 3L9, Kanada
-
Peter Taylor
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre,, Oxford, Großbritannien
-
Steven H. Zuckerman
- Eli Lilly & Company, Indianapolis, USA
-
Douglas Schlichting
- Eli Lilly & Co. Corporate Ct., Indianapolis, United States of America
-
Eric Nantz
- Eli Lilly & Company, Indianapolis, USA
-
Scott Beattie
- Global Statistical Sciences / Autoimmune Platform, Eli Lilly and Company, Indianapolis, United States of America
-
William Macias
- Eli Lilly & Co. Corporate Ct,, Indianapolis, United States of America
-
Thorsten Holzkämper
- Lilly Deutschland GmbH, Bad Homburg
| Published: | September 1, 2015 |
|---|
Outline
Text
Introduction: Treatment with baricitinib, an oral JAK1/JAK2 inhibitor, demonstrated improvements in signs and symptoms of RA through 52 wks in a Phase 2b study [1] and also in dose- and time-dependent changes in serum lipids, LDL particle size, and HDL and VLDL particle numbers [2].
Methods: Patients (pts) with RA were randomized to QD blinded treatment with placebo (PBO) (n=98) or baricitinib 1 mg (n=49), 2 mg (n=52), 4 mg (n=52), or 8 mg (n=50) for 12 wks. Apolipoprotein content was assessed at Wks 4/12 for PBO and 4-/8-mg baricitinib groups.
Results: Pts who continued treatment with baricitinib through 52 wks maintained stable cholesterol and triglyceride profiles with no further changes beyond Wks 12/24. Increases in apolipoprotein A-I, apolipoprotein B, and total apolipoprotein CIII through 12 wks were observed with 4-/8-mg baricitinib with no increase in LDL-associated apolipoprotein CIII. Baricitinib treatment also demonstrated a reduction in HDL-associated SAA at 4-/8-mg doses while a reduction in Lp(a) was observed only with 8-mg baricitinib (all p<0.05). These apolipoprotein changes coincided with the increases in serum lipids apparent by Wk 4. In pts treated across all doses of baricitinib, change in HDL cholesterol correlated with absolute DAS28-CRP score at Wk 12 (r=-0.32, p<0.001) and the change from baseline to Wk 12 in DAS28-CRP (r=-0.28, p<0.001). Specifically, pts achieving DAS28-CRP <2.6 and larger decreases in DAS28-CRP demonstrated larger increases in HDL cholesterol.
Conclusion: Further studies are necessary to determine if these changes influence long-term cardiovascular outcomes.
