title: Relationship between exposure to tumour necrosis factor inhibitor therapy and incidence and severity of myocardial infarction in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Patients with rheumatoid arthritis (RA) are at increased risk of myocardial infarction (MI) compared with subjects without RA, with the increased risk driven potentially by inflammation. Tumour necrosis factor inhibitors (TNFi) may modulate the risk and severity of MI. We compared the risk and severity of MI in patients treated with TNFi with that in those receiving synthetic disease-modifying antirheumatic drugs (sDMARDs).
  
  
  METHODS
  This analysis included patients with RA recruited from 2001 to 2009 to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis starting TNFi (etanercept/infliximab/adalimumab) and a biologic-naïve comparator cohort receiving sDMARD. All patients were followed via physician and patient questionnaires and national death register linkage. Additionally, all patients were linked to the Myocardial Ischaemia National Audit Project, a national registry of hospitalisations for MI. Patients were censored at first verified MI, death, 90 days following TNFi discontinuation, last physician follow-up or 20 April 2010, whichever came first. The risk of first MI was compared between cohorts using COX regression, adjusted with propensity score deciles (PD). MI phenotype and severity were compared using descriptive statistics. 6-month mortality post MI was compared using logistic regression.
  
  
  RESULTS
  252 verified first MIs were analysed: 58 in 3058 patients receiving sDMARD and 194 in 11 200 patients receiving TNFi (median follow-up per person 3.5 years and 5.3 years, respectively). The PD-adjusted HR of MI in TNFi referent to sDMARD was 0.61 (95% CI 0.41 to 0.89). No statistically significant differences in MI severity or mortality were observed between treatment groups.
  
  
  CONCLUSIONS
  Patients with RA receiving TNFi had a decreased risk of MI compared with patients with RA receiving sDMARD therapy over the medium term. This might be attributed to a direct action of TNFi on the atherosclerotic process or better overall disease control.
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Audrey S L
authors.initials: AS
authors.lastname: Low
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Deborah P M
authors.identifier: http://orcid.org/0000-0002-8625-1200
authors.initials: DP
authors.lastname: Symmons
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Lunt
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Louise K
authors.initials: LK
authors.lastname: Mercer
authors.affiliation: Division of Epidemiology and Biostatistics, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.|York Teaching Hospital NHS Foundation Trust, York, UK.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Gale
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Kath D
authors.initials: KD
authors.lastname: Watson
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: William G
authors.identifier: http://orcid.org/0000-0001-5881-4857
authors.initials: WG
authors.lastname: Dixon
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Kimme L
authors.identifier: http://orcid.org/0000-0001-8242-9262
authors.initials: KL
authors.lastname: Hyrich
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D000069285:Infliximab / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000401:mortality; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
keywords: Anti-TNF; Cardiovascular Disease; Epidemiology; Rheumatoid Arthritis