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

Cem Gabay, Iain B McInnes, Arthur Kavanaugh, Katie Tuckwell, Micki Klearman, Jennifer Pulley, Naveed Sattar, Cem Gabay, Iain B McInnes, Arthur Kavanaugh, Katie Tuckwell, Micki Klearman, Jennifer Pulley, Naveed Sattar

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.

Keywords: Cardiovascular Disease; Inflammation; Lipids; Rheumatoid Arthritis.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Figures

Figure 1
Figure 1
Change from baseline to week 8 in HDL-SAA (A, bio-repository population), sPLA2 IIA (B, bio-repository population) and Lp(a) (C, safety population)—patient-level data. ADA, adalimumab; HDL-SAA, high-density lipoprotein-associated serum amyloid A; IV, intravenous; Lp(a), lipoprotein (a); sPLA2 IIA, secretory phospholipase A2 IIA; q2w, every 2 weeks; q4w, every 4 weeks; SC, subcutaneous; TCZ, tocilizumab.

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