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Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case–control analysis
  1. William G Dixon1,
  2. Michal Abrahamowicz2,3,
  3. Marie-Eve Beauchamp3,
  4. David W Ray4,
  5. Sasha Bernatsky5,
  6. Samy Suissa6,
  7. Marie-Pierre Sylvestre7,8
  1. 1Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  2. 2Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada
  3. 3Division of Clinical Epidemiology, McGill University Health Center, Montreal, Canada
  4. 4Endocrine Sciences Research Group, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
  5. 5McGill University Health Centre, Department of Medicine, Divisions of Clinical Epidemiology and Rheumatology, Montreal, Canada
  6. 6Centre For Clinical Epidemiology, Lady Davis Institute – Jewish General Hospital, McGill University, Montreal, Canada
  7. 7Research Centre of the University of Montreal Hospital Centre, Montreal, Canada
  8. 8Department of Social and Preventive Medicine, Université de Montréal, Montréal, Canada
  1. Correspondence to William Dixon, Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, University of Manchester, Manchester, Stopford Building, Manchester M13 9PT, UK; will.dixon{at}manchester.ac.uk

Abstract

Objectives To explore the relationship of serious infection risk with current and prior oral glucocorticoid (GC) therapy in elderly patients with rheumatoid arthritis (RA).

Methods A case-control analysis matched 1947 serious infection cases to five controls, selected from 16207 RA patients aged ≥65 between 1985–2003 in Quebec, Canada. Adjusted odds ratios for infection associated with different GC patterns were estimated using conventional models and a weighted cumulative dose (WCD) model.

Results The WCD model predicted risks better than conventional models. Current and recent GC doses had highest impact on current risk. Doses taken up to 2.5 years ago were also associated with increased risk, albeit to a lesser extent. A current user of 5mg prednisolone had a 30%, 46% or 100% increased risk of serious infection when used continuously for the last 3 months, 6 months or 3 years, respectively, compared to a non-user. The risk associated with 5mg prednisolone taken for the last 3 years was similar to that associated with 30mg taken for the last month. Discontinuing a two-year course of 10mg prednisolone six months ago halved the risk compared to ongoing use.

Conclusions GC therapy is associated with infection risk in older patients with RA. The WCD model provided more accurate risk estimates than conventional models. Current and recent doses have greatest impact on infection risk, but the cumulative impact of doses taken in the last 2–3 years still affects risk. Knowing how risk depends on pattern of GC use will contribute to an improved benefit/harm assessment.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl

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Footnotes

  • Contributors WGD and MA conceived and designed the study; SS and SB acquired the data; MEB, MA and MPS analysed the data; WGD, MA and MEB interpreted the data and drafted the article; DWR, SS, SB and MPS contributed to interpretation of the data and critical revision of the manuscript for important intellectual content. All researchers had access to all the data in the study. WGD is the guarantor.

  • Funding The database acquisition was funded by a grant to SS from the Canadian Institutes of Health Research (CIHR) and the Canadian Foundation for Innovation. The analyses were supported by the CIHR grant MOP-81275 (PI: MA). WGD was supported by an MRC Clinician Scientist Fellowship (G0902272).

  • Competing interests None.

  • Ethical approval The McGill University Institutional Review Board approved the study.

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

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