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

Abstract

ObjectiveCompare changes in lipids and lipid-associated cardiovascular (CV) risk markers in patients with rheumatoid arthritis (RA) treated with tocilizumab or adalimumab.MethodsPost-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.ResultsThe 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.ConclusionLDL-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 numberNCT01119859.; post-results

Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications

“…CHF=congestive heart failure; COX=cyclooxygenase; CVD=cardiovascular disease; DMARDs=disease modifying anti-rheumatic drugs; HCQ=hydroxychloroquine; LDL=low density lipoprotein; MI=myocardial infarction; NSAID=non-steroidal anti-inflammatory drug; RA=rheumatoid arthritis; RR=relative risk; TNF=tumor necrosis factor1790949596979899100101102103104105106107108109110111112113114115116117118119120121122123124125126127…”

“…Ultimately, closer inspection illustrated that lipid changes occurring in the wake of different DMARD treatments likely reflect improvement in inflammation rather than a unique pro-atherogenic drug effect 144. Although reductions in inflammation seem to have generic effects on lipid profiles, post hoc analysis of the ADACTA trial, a RCT of 326 rheumatoid arthritis patients comparing the efficacy of tocilizumab and adalimumab, showed differing effects of these biologics on lipids 113. After eight weeks of tocilizumab, greater increases were seen in total cholesterol, HDL, LDL, triglycerides, and total cholesterol/HDL compared with adalimumab.…”

Pathogenetic insights from the treatment of rheumatoid arthritis

“…levels and the disease-related changes of lipid particle composition revert upon IL-6R pathway inhibition [81]. Most importantly control of inflammation in RA has shown to affect cardiovascular risk: Methotrexate moderately lowers cardiovascular risk in RA [82].…”

A psoriatic arthritis patient who developed hypertriglyceridemia while receiving adalimumab treatment

“…1 Anti-TNF agents have prominent effect on inflammatory diseases and they probably have various effects on lipid metabolism. 1 A few studies investigated lipid profile effects of anti-TNF agents, but they have conflicting data.…”

“…1 Anti-TNF agents have prominent effect on inflammatory diseases and they probably have various effects on lipid metabolism. 1 A few studies investigated lipid profile effects of anti-TNF agents, but they have conflicting data. [2][3][4] In this case, we present a male patient who developed evident hypertriglyceridemia while receiving ADA treatment.…”