Risk of skin and soft tissue infections (including shingles) in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register
- James B Galloway1,
- Louise K Mercer1,
- Alison Moseley1,2,
- William G Dixon1,
- Andrew P Ustianowski3,
- Matthew Helbert4,
- Kath D Watson1,
- Mark Lunt1,
- Kimme L Hyrich1,
- Deborah PM Symmons1
- 1Arthritis Research UK Epidemiology Unit, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK
- 2University of Birmingham, Birmingham, UK
- 3Department of Infectious Diseases, North Manchester General Hospital, Manchester, UK
- 4Department of Immunology, Central Manchester NHS Foundation Trust, Manchester, UK
- Correspondence to Dr Kimme Hyrich, Arthritis Research UK Epidemiology Unit, Manchester Academic Health Sciences Centre, Stopford Building, Oxford Road, The University of Manchester, Manchester, M13 9PT, UK; .
Contributors JBG and LKM were involved in all aspects of this research. KLH and DPMS are both principal investigators for the BSRBR and oversaw this research. AM worked on case verification and data analysis. WGD, MH and APU advised on the analysis and contributed to writing the manuscript. ML provided statistical support. KDW contributed to data collection, analysis and editing the manuscript. The BSRBR control centre consortium was involved in the recruitment of patients to the control arm.
- Accepted 25 March 2012
- Published Online First 24 April 2012
Introduction Anti-tumour necrosis factor (TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). In 2001, BSRBR was established to evaluate the safety of these agents. This paper addresses the safety of anti-TNF therapy in RA with specific reference to serious skin and soft tissue infections (SSSI) and shingles.
Methods A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses.
Results The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)).
Conclusion A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population.
Funding Funding for this project was provided by the British Society for Rheumatology.
Competing interests The BSR commissioned the Biologics Register (BSRBR) as a UK-wide national project to investigate the safety of biological 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, Biovitrum, Merk Sharpe & Dohme, Pfizer and Roche. This income finances a wholly separate contract between the BSR and the University of Manchester. 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. The authors declare no other competing interests.
Ethics approval Ethics approval for this study was obtained from the Multicentre Research Ethics Committee for the northwest of England.
Provenance and peer review Not commissioned; externally peer reviewed.
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