Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis

Gabay, C., McInnes, I. B. , Kavanaugh, A., Tuckwell, K., Klearman, M., Pulley, J. and Sattar, N. (2016) Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases, 75(10), pp. 1806-1812. (doi: 10.1136/annrheumdis-2015-207872) (PMID:26613768) (PMCID:PMC5036214)

Abstract

Objective: Compare changes in lipids and lipid-associated cardiovascular (CV) risk markers in patients with rheumatoid arthritis (RA) treated with tocilizumab or adalimumab. Methods: Post-hoc analysis was performed in patients with RA who received tocilizumab intravenously every 4 weeks or adalimumab subcutaneously every 2 weeks for 24 weeks in the ADACTA trial. Lipid and lipid-associated CV risk biomarkers, including high-density lipoprotein-associated serum amyloid-A (HDL-SAA), secretory phospholipase A2 IIA (sPLA2 IIA) and lipoprotein(a) (Lp(a)), were measured at baseline and at week 8. Results: The study included 162 patients treated with tocilizumab and 162 patients treated with adalimumab; HDL-SAA and sPLA2 IIA were measured in a subpopulation of 87 and 97 patients, respectively. Greater increases in mean low-density lipoprotein cholesterol (LDL-C) (0.46 mmol/L (95% CI 0.30 to 0.62)), high-density lipoprotein cholesterol (HDL-C) (0.07 mmol/L (0.001 to 0.14)), total cholesterol (TC) (0.67 mmol/L (0.47 to 0.86)), triglycerides (0.24 mmol/L (0.10 to 0.38)) and TC:HDL ratio (0.27 (0.12 to 0.42)) occurred with tocilizumab from baseline to 8 weeks. HDL-SAA, sPLA2 IIA and Lp(a) decreased more with tocilizumab than adalimumab. Median changes from baseline to week 8 were –3.2 and –1.1 mg/L (p=0.0077) for HDL-SAA and –4.1 and –1.3 ng/mL (p<0.0001) for sPLA2 IIA; difference in adjusted means was –7.12 mg/dL (p<0.0001) for Lp(a). Similar results were observed in efficacy responders and non-responders per American College of Rheumatology and European League against Rheumatism criteria. Conclusion: LDL-C and HDL-C increased more with tocilizumab than adalimumab. HDL-SAA, sPLA2 IIA and Lp(a) decreased more with tocilizumab. Lipid change effects of interleukin-6 and tumour necrosis factor (TNF) inhibition, manifest by their net impact on lipids and lipoproteins, are not synonymous; the clinical significance is unclear and requires further study. Trial registration number: NCT01119859.; post-results.

• Item Type: Articles
• Additional Information: F. Hoffmann-La Roche provided funding for writing assistance.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Sattar, Professor Naveed
• Authors: Gabay, C., McInnes, I. B., Kavanaugh, A., Tuckwell, K., Klearman, M., Pulley, J., and Sattar, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Annals of the Rheumatic Diseases
• Publisher: BMJ Publishing Group
• ISSN: 0003-4967
• ISSN (Online): 1468-2060
• Published Online: 27 November 2015
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Annals of the Rheumatic Diseases 75(10): 1806-1812
• Publisher Policy: Reproduced under a Creative Commons License