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Extended report
Relationship between exposure to tumour necrosis factor inhibitor therapy and incidence and severity of myocardial infarction in patients with rheumatoid arthritis
  1. Audrey S L Low1,
  2. Deborah P M Symmons1,2,
  3. Mark Lunt1,
  4. Louise K Mercer1,
  5. Chris P Gale3,4,
  6. Kath D Watson1,
  7. William G Dixon1,
  8. Kimme L Hyrich1
  9. on behalf of the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) and the BSRBR Control Centre Consortium
    1. 1Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK
    2. 2NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
    3. 3Division of Epidemiology and Biostatistics, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
    4. 4York Teaching Hospital NHS Foundation Trust, York, UK
    1. Correspondence to Professor Kimme Hyrich, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, Manchester M13 9PT, UK; Kimme.Hyrich{at}


    Objectives 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.

    • Rheumatoid Arthritis
    • Epidemiology
    • Anti-TNF
    • Cardiovascular Disease

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    • Handling editor Tore K Kvien

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    • Collaborators BSRBR Control Centre Consortium: The BSRBR Control Centre Consortium consists of the following institutions (all in the UK): Antrim Area Hospital, Antrim (Dr Nicola Maiden); Cannock Chase Hospital, Cannock Chase (Dr Tom Price); Christchurch Hospital, Christchurch (Dr Neil Hopkinson); Royal Derby Hospital, Derby (Dr Sheila O'Reilly), Dewsbury and District Hospital, Dewsbury (Dr Lesley Hordon); Freeman Hospital, Newcastle upon Tyne (Dr Ian Griffiths); Gartnavel General Hospital, Glasgow (Dr Duncan Porter); Glasgow Royal Infirmary, Glasgow (Professor Hilary Capell); Haywood Hospital, Stoke-on-Trent (Dr Andy Hassell); Hope Hospital, Salford (Dr Romela Benitha); King's College Hospital, London (Dr Ernest Choy); Kings Mill Centre, Sutton-in Ashfield (Dr David Walsh); Leeds General Infirmary, Leeds (Professor Paul Emery); Macclesfield District General Hospital, Macclesfield (Dr Susan Knight); Manchester Royal Infirmary, Manchester (Professor Ian Bruce); Musgrave Park Hospital, Belfast (Dr Allister Taggart); Norfolk and Norwich University Hospital, Norwich (Professor David Scott); Poole General Hospital, Poole (Dr Paul Thompson); Queen Alexandra Hospital, Portsmouth (Dr Fiona McCrae); Royal Glamorgan Hospital, Glamorgan (Dr Rhian Goodfellow); Russells Hall Hospital, Dudley (Professor George Kitas); Selly Oak Hospital, Selly Oak (Dr Ronald Jubb); St Helens Hospital, St Helens (Dr Rikki Abernethy); Weston General Hospital, Weston-super-Mare (Dr Shane Clarke/Dr Sandra Green); Withington Hospital, Manchester (Dr Paul Sanders); Withybush General Hospital, Haverfordwest (Dr Amanda Coulson); North Manchester General Hospital (Dr Bev Harrison); Royal Lancaster Infirmary (Dr Marwan Bukhari) and The Royal Oldham Hospital (Dr Peter Klimiuk).

    • Funding This work was supported by the BSR. The BSR commissioned the BSRBR-RA as a UK-wide national project to investigate the safety of biological agents in routine medical practice. BSR receives restricted income from UK pharmaceutical companies, presently Abbvie, Celltrion, Hospira, Pfizer, UCB and Roche, and in the past Swedish Orphan Biovitrum and Merck. This income finances a wholly separate contract between the BSR and the University of Manchester. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. Members of the University of Manchester team, BSR trustees, committee members and staff complete an annual declaration in relation to conflicts of interest. All relevant information regarding serious adverse events outlined in the manuscript have been reported to the appropriate companies as per the contractual agreements/standard operating procedures. The British MINAP is commissioned by the Health Quality Improvement Partnership as part of the National Clinical Audit and Patient Outcomes Programme. CPG is funded by the National Institute for Health Research (NIHR-CTF-2014-03-03) as Associate Professor and Honorary Consultant Cardiologist. WGD was supported by an MRC Clinician Scientist Fellowship (G0902272). DPMS and KH are the principal investigators of the BSRBR-RA and had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    • Competing interests KH has received honoraria from Pfizer and Abbvie.

    • Ethics approval UK North West Multicentre Research Ethics Committee (reference no: 00/8/53).

    • Provenance and peer review Not commissioned; externally peer reviewed.

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