Extended report glucocorticoid therapy more than 45 days before an infection would have much less inﬂuence upon infection risk than recent or current therapy. The low RR of 1.20 is in the range of values that might rea- sonably be explained by bias.22 Clinicians may prescribe anti- infectives at different thresholds to patients under treatment with glucocorticoid or DMARD therapy. For example, a patient with a sore throat and mild temperature may be more likely to receive anti-infectives if immunosuppressed. This would increase the relative proportion of cases exposed to glucocor- ticoid and DMARD therapy, and might explain some of the observed effect. We cannot assess whether this explains the whole effect, although it seems unlikely. Another concern is confounding by disease severity, in which patients with high disease activity and thus at higher risk of infection9 are more likely to be prescribed glucocorticoid therapy. Disease severity is not measured directly in RAMQ, so we used surrogate mark- ers that were available, including the number of rheumatologist visits in the preceding 6 months and concomitant NSAID use. Because these are imperfect surrogates, residual confounding will exist. We can, nonetheless, explore whether different lev- els of disease severity in glucocorticoid-exposed and unexposed patients can wholly explain the observed relationship (ie, reduce the aRR from 1.2 to 1) using the ‘rule-out approach’.23 Assuming a baseline prevalence of ‘high disease severity’ of 20% in the whole cohort and a RR of NSI of 1.27 for this confounder,9 dis- ease severity cannot explain the observed aRR of 1.20. Even if we assume a doubling of NSI for the 20% of patients with ‘high disease severity’, this unmeasured confounder would have to be nearly four times more common in glucocorticoid-exposed patients to explain fully the observed aRR of 1.2. However, while theoretically possible, no binary measure of disease severity has yet been reported with such a strong association. Finally, there may be confounding by contraindication, in which a patient with high comorbidity is considered too ‘high risk’ for traditional DMARD therapy and is instead prescribed glucocor- ticoid therapy. We attempted to adjust for this in the analysis. The results of the dose-dependent analysis suggest that the increased risk of NSI exists at a daily dose of 5–10 mg PEQ. It may even be present at doses less than 5 mg, although this result was inconclusive (aRR 1.10, 0.99 to 1.22). It is interesting to com- pare the effect sizes between oral glucocorticoid therapy and methotrexate. At any dose, glucocorticoid therapy was associ- ated with a higher RR of NSI compared with that seen with methotrexate. This is important to note as some clinicians see steroids as the ‘safer choice’ for older patients. The preferential prescription of glucocorticoid therapy over methotrexate may therefore be misguided with respect to infections, even at low doses. Any comparison between the two drugs must, of course, take account of all adverse drug reactions and not just NSI. Nonetheless, patients treated with glucocorticoid therapy have repeatedly been shown to have higher rates of serious infec- tion than patients treated with methotrexate in observational studies.6 9–12 Older patients are also at high risk of other glu- cocorticoid-associated adverse events such as osteoporosis and cardiovascular disease. The comparative safety of glucocorticoid and DMARD therapy, in particular in older patients and patients with existing comorbidity, warrants careful consideration. In summary, we have shown that glucocorticoid therapy is associated with a modest relative, but high attributable, risk of NSI. While some of this association may be explained by residual confounding, clinicians should nonetheless consider carefully the risks of glucocorticoid therapy in older patients, even at low doses. Funding WGD was partly supported by a travel award from the Dickinson Trust Scholarship Fund, Central Manchester Foundation Trust. The database acquisition was funded by a grant to SS from the Canadian Institutes of Health Research (CIHR) and the Canadian Foundation for Innovation (CFI). Contributors Study design: WGD, SS; data acquisition: SS, SB; manuscript preparation: WGD, SB, SS; statistical analysis: AK. Ethics approval This study was conducted with the approval of the McGill University Institutional Review Board. Provenance and peer review Not commissioned; externally peer reviewed. REFERENCES 1. Hench PS, Kendall EC, Slocumb CH, et al. Effects of cortisone acetate and pituitary ACTH on rheumatoid arthritis, rheumatic fever and certain other conditions. 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