Extended report ▶ Supplementary appendix A is published online only in ﬁle 1. To view this ﬁle please visit the journal online (http://ard.bmj. com). 1Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre,The University of Manchester, Manchester, UK 2Centre for Clinical Epidemiology, Lady Davis Institute – Jewish General Hospital, McGill University, Montreal, Canada 3Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Canada Correspondence to Dr W G Dixon, Arthritis Research UK Epidemiology Unit, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK; will.dixon@manchester.ac.uk Accepted 2 January 2011 Published Online First 1 February 2011 956 The inﬂuence of systemic glucocorticoid therapy upon the risk of non-serious infection in older patients with rheumatoid arthritis: a nested case–control study W G Dixon,1,2 A Kezouh,2 S Bernatsky,3 S Suissa2 ABSTRACT Background Glucocorticoid therapy is strongly associated with an elevated risk of serious infections in patients with rheumatoid arthritis (RA). The association between glucocorticoids and common non-serious infections (NSI) is not well studied. Methods A cohort of 16 207 patients with RA aged over 65 years was assembled using administrative data from Quebec. Glucocorticoid and disease-modifying antirheumatic drug (DMARD) therapy were identiﬁed from drug dispensing records. NSI cases were deﬁned as ﬁrst occurrence of a community physician billing code for infection or community-dispensed anti-infectives. A nested case–control analysis was performed considering drugs dispensed within 45 days of the index date, adjusting for age, sex, markers of disease severity, DMARD and comorbidity. Results For 13 634 subjects, a NSI occurred during 28 695 person-years of follow-up, generating an incidence rate of 47.5/100 person-years. The crude rate of NSI in glucocorticoid-exposed and unexposed person time was 52.4 and 38.8/100 person-years, respectively. Glucocorticoid therapy was associated with an adjusted RR of 1.20 (95% CI 1.15 to 1.25). A dose response was seen, the adjusted RR increasing from 1.10 (<5 mg prednisolone/day) to 1.85 for doses greater than 20 mg/day. All glucocorticoid risk estimates (including <5 mg/day) were higher than that seen for methotrexate (adjusted RR 1.00; 0.95 to 1.04). Conclusion Glucocorticoid therapy is associated with an increased risk of NSI. The magnitude of risk increases with dose, and is higher than that seen with methotrexate, although residual confounding may exist. While the RR is low at 1.20, the absolute risk is high with one additional infection seen for every 13 patients treated with glucocorticoids for 1 year. Glucocorticoid therapy was introduced as a treat- ment for patients with rheumatoid arthritis (RA) nearly 60 years ago.1 Approximately one third of patients with RA are current users, and two thirds of patients have ever used steroids.2 Although glu- cocorticoid therapy improves the symptoms of active RA3 and modiﬁes disease progression,4 there have long been concerns about safety. One of the major risks associated with glucocorticoid therapy is infection, along with others including cardiovas- cular disease, diabetes and osteoporosis.5 The association between glucocorticoid therapy and serious infection (generally deﬁned as infection leading to hospitalisation, intravenous antibiotics, signiﬁcant loss of function or disability or death) is now well established in observational studies.6–15 Randomised clinical trials are often too small and thus underpowered to detect risks of serious infec- tions. The risk of infection is dose-dependent,10 11 13 although it is not clear if there is a threshold below which glucocorticoid therapy is safe. Comparisons with the risk associated with other traditional disease-modifying antirheumatic drugs (DMARD) suggest glucocorticoid therapy has a higher RR.6–12 To date, little research has explored the associa- tion between glucocorticoid therapy and non-seri- ous infection (NSI) in patients with RA. Although these events are not life-threatening, the burden of NSI is high. Non-serious respiratory infections account for 300–400 general practice consultations annually per 1000 registered patients in the UK.16 Even a modest increase in the RR of NSI with glu- cocorticoid therapy could therefore represent a large increase in the absolute or attributable risk and a signiﬁcant health burden. Our primary aim was to test the hypothesis that systemic glucocorticoid therapy is associated with an increased risk of NSI in patients with RA com- pared with patients with RA not treated with glu- cocorticoids using a nested case–control analysis. Secondary aims were to estimate the attributable risk associated with glucocorticoids, explore any dose-dependent risk and to compare the glucocor- ticoid-associated risk with the risk associated with other DMARD treatments. METHODS A cohort study and nested case–control analysis was conducted to examine the inﬂuence of sys- temic glucocorticoid therapy upon the risk of NSI in patients with RA. Ethical approval was obtained from the McGill University Institutional Review Board. Study base Patients with RA were assembled from the admin- istrative databases of the Régie de l’assurance mala- die du Québec (RAMQ) and the Ministry of Health’s Maintenance et Exploitation des Données pour l’Étude de la Clientèle Hospitalière (MEDECHO). The RAMQ is responsible for administering uni- versal healthcare services for the province of Québec, Canada. It contains three databases linked by an individual’s unique health insurance number: a demographic database, a medical services data- base and a prescription database. The demographic Ann Rheum Dis 2011;70:956–960. doi:10.1136/ard.2010.144741