title: Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  NCT01119859.; post-results.
authors.affiliation: University Hospitals, Geneva, Switzerland.
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: University of California, San Diego, California, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Tuckwell
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: Micki
authors.initials: M
authors.lastname: Klearman
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pulley
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage*; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D017270:Lipoprotein(a) / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D054497:Phospholipases A2, Secretory / Q000097:blood; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D008055:Lipids; D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein; D054497:Phospholipases A2, Secretory; D000068879:Adalimumab; C502936:tocilizumab
keywords: Cardiovascular Disease; Inflammation; Lipids; Rheumatoid Arthritis