Influence of anti-TNF therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the British Society for Rheumatology Biologics Register
- 1Arthritis Research UK Epidemiology Unit, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
- 2British Society for Rheumatology Biologics Register, Manchester, UK
- Correspondence to Professor Deborah Symmons, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK;
Contributors WGD, study design, data analysis, interpretation, writing; KLH, study design, data management, interpretation, writing; KDW, study design, data management; ML, study design, data analysis; DPMS, study design, data management, interpretation, writing. The British Society for Rheumatology (BSR) commissioned the Biologics Register (BSRBR) as a UK-wide national project to investigate the safety of biologic agents in routine medical practice. DPMS and KLH are principal investigators on the BSRBR. BSR receives restricted income from UK pharmaceutical companies, presently Abbott Laboratories, Amgen, Schering Plough and Wyeth Pharmaceuticals. This income finances a wholly separate contract between the BSR and the University of Manchester who provide and run the BSRBR data collection, management and analysis services. The principal investigators and their team have full academic freedom and are able to work independently of pharmaceutical industry influence. All decisions concerning analyses, interpretation and publication are made autonomously of any industrial contribution. Members of the Manchester team, BSR trustees, committee members and staff complete an annual declaration in relation to conflicts of interest.
- Accepted 3 December 2009
- Published Online First 5 May 2010
Background Anti-tumour necrosis factor (anti-TNF) therapy has been associated with reports of rapid severe progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, reports also exist of favourable responses to anti-TNF therapy in patients with ILD. The aim of this study was to examine the influence of anti-TNF therapy on mortality in patients with pre-existing RA-ILD.
Methods Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, 367 patients with pre-existing RA-ILD were identified (299 treated with anti-TNF therapy and 68 treated with traditional disease-modifying antirheumatic drugs (DMARDs)).
Results 70/299 patients (23%) in the anti-TNF cohort died after a median follow-up of 3.8 years compared with 14/68 (21%) in the DMARD cohort after a median follow-up of 2.1 years. The mortality was 68 deaths/1000 person years (pyrs) (95% CI 53 to 86) in the anti-TNF cohort and 92/1000 pyrs (95% CI 50 to 155) in the DMARD cohort, generating an age- and sex-adjusted mortality rate ratio (aMRR) of 1.26 (95% CI 0.69 to 2.31). After further adjustment for potential confounders, the aMRR fell to 0.81 (95% CI 0.38 to 1.73) for the anti-TNF cohort compared with the DMARD cohort. RA-ILD was the underlying cause of death in 15/70 (21%) and 1/14 (7%) patients in the anti-TNF and DMARD cohorts, respectively.
Conclusion The mortality in patients with RA-ILD is not increased following treatment with anti-TNF therapy compared with traditional DMARDs. The proportion of deaths attributable to RA-ILD is higher in patients treated with anti-TNF therapy, although reporting bias may exist.
BSRBR Control Centre Consortium Antrim Area Hospital, Antrim (Dr Nicola Maiden); Cannock Chase Hospital, Cannock Chase (Dr Tom Price); Christchurch Hospital, Christchurch (Dr Neil Hopkinson); Derbyshire Royal Infirmary, 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 (Dr Ian Bruce); Musgrave Park Hospital, Belfast (Dr Allister Taggart); Norfolk and Norwich University Hospital, Norwich (Professor David Scott); Poole General Hospital, Poole (Professor 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); Withington Hospital, Manchester (Dr Paul Sanders); Withybush General Hospital, Haverfordwest (Dr Amanda Coulson).
Competing interests None.
Ethics approval Ethical approval for this study was obtained in December 2000 from the Multicentre Research Ethics Committee (MREC) for the Northwest of England.
Provenance and peer review Not commissioned; externally peer reviewed.