title: An evaluation of risk factors for major adverse cardiovascular events during tocilizumab therapy.
abstract: OBJECTIVE
  To evaluate associations between lipid levels, inflammation, and rheumatoid arthritis (RA) disease activity, at baseline and during treatment, with the risk of major adverse cardiovascular events (MACE) in tocilizumab-treated patients with RA.
  
  
  METHODS
  In retrospective post hoc analyses, data were pooled for 3,986 adult patients with moderate to severe RA who received ≥1 dose of tocilizumab (4 mg/kg or 8 mg/kg) intravenously every 4 weeks in randomized controlled trials and extension studies. Cox proportional hazards modeling was used to evaluate associations between baseline characteristics and posttreatment changes in laboratory and disease characteristics (week 24) and change in disease activity and laboratory values from baseline to week 24 with the risk of future MACE during extended followup.
  
  
  RESULTS
  We identified 50 independently adjudicated cases of MACE during 14,683 patient-years of followup (0.34 MACE cases/100 patient-years). At baseline, age, a history of cardiac disorders, the Disease Activity Score in 28 joints (DAS28), and the total cholesterol:high-density lipoprotein cholesterol ratio were independently associated with MACE in multivariable models (P < 0.05 for all). During treatment, a higher DAS28 and higher swollen and tender joint counts at week 24 were associated with future MACE. In separate models, greater reductions in the DAS28 and joint counts from baseline to week 24 were inversely associated with future MACE; changes in lipid parameters were not statistically significantly associated with the risk of MACE.
  
  
  CONCLUSIONS
  In this population of patients treated with tocilizumab, an association was observed between the baseline total cholesterol:high-density lipoprotein cholesterol ratio and an increased risk of MACE. The risk of MACE while receiving treatment, however, was associated with control of disease activity but not lipid changes. Larger studies are needed to confirm these findings.
authors.affiliation: Genentech, South San Francisco, California.
authors.forename: Vijay U
authors.initials: VU
authors.lastname: Rao
authors.forename: Andrey
authors.initials: A
authors.lastname: Pavlov
authors.forename: Micki
authors.initials: M
authors.lastname: Klearman
authors.forename: David
authors.initials: D
authors.lastname: Musselman
authors.forename: Jon T
authors.initials: JT
authors.lastname: Giles
authors.forename: Joan M
authors.initials: JM
authors.lastname: Bathon
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Janet S
authors.initials: JS
authors.lastname: Lee
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab