Table 3 Effect of current glucocorticoid therapy upon non-serious infection (billing code or anti-infective prescription), stratiﬁed by mode of administration (oral only, injection only, oral or injection) and dose Cases (n=13 634) Controls (n=68 170) Crude RR (95% CI) RR, adjusted for age and sex only (95% CI) RR, adjusted for age and sex and DMARD (95% CI) Oral glucocorticoid exposure 37.9 within past 45 days Average daily dose of glucocorticoid therapy <5 mg PEQ 3.2 5–9.9 mg 17.8 10–14.9 mg 9.5 15–19.9 mg 2.7 ≥20 mg 4.7 Systemic glucocorticoid 2.2 injection within past 45 days Any glucocorticoid: oral or injection 39.2 32.5 3.1 17.1 7.9 2.1 2.3 1.8 33.7 1.28 (1.23 to 1.33) 1.28 (1.23 to 1.33) 1.28 (1.23 to 1.34) 1.13 (1.01 to 1.25) 1.15 (1.09 to 1.20) 1.33 (1.25 to 1.42) 1.41 (1.25 to 1.58) 2.33 (2.11 to 2.56) 1.18 (1.04 to 1.34) 1.13 (1.01 to 1.25) 1.15 (1.09 to 1.20) 1.33 (1.25 to 1.42) 1.41 (1.25 to 1.58) 2.33 (2.11 to 2.56) 1.18 (1.04 to 1.34) 1.28 (1.23 to 1.33) 1.28 (1.23 to 1.33) 1.13 (1.02 to 1.26) 1.15 (1.10 to 1.21) 1.34 (1.26 to 1.44) 1.40 (1.25 to 1.58) 2.27 (2.06 to 2.50) 1.18 (1.04 to 1.34) 1.29 (1.24 to 1.34) Numbers are percentages unless otherwise stated. *Adjusted for all a priori confounders listed in table 2. DMARD, disease-modifying antirheumatic drug; PEQ, prednisolone equivalent dose. Table 4 Crude and aRR of non-serious infection, by current DMARD use Extended report Adjusted RR* (95% CI) 1.20 (1.15 to 1.25) 1.10 (0.99 to 1.22) 1.10 (1.04 to 1.16) 1.25 (1.17 to 1.34) 1.26 (1.12 to 1.42) 1.85 (1.68 to 2.05) 1.07 (0.94 to 1.22) 1.19 (1.14 to 1.24) Cases (n=13 634) Controls (n=68 170) aRR, model 1 (95% CI) aRR, model 2 (95% CI) Current DMARD use Methotrexate Sulfasalazine Leﬂunomide CQ/HCQ Azathioprine Cyclophosphamide Gold Anti-tumour necrosis factor therapy Others 33.3 2.4 0.3 29.4 1.9 1.7 7.1 0.1 1.8 33.0 3.0 0.3 30.7 1.5 0.7 6.5 0.1 1.7 0.98 (0.94 to 1.03) 0.81 (0.72 to 0.91) 1.07 (0.76 to 1.49) 0.91 (0.87 to 0.96) 1.13 (0.99 to 1.31) 2.86 (2.05 to 3.99) 1.13 (1.04 to 1.23) 1.41 (0.83 to 2.39) 1.08 (0.93 to 1.25) 1.00 (0.95 to 1.04) 0.79 (0.70 to 0.89) 1.00 (0.71 to 1.39) 0.93 (0.89 to 0.98) 1.05 (0.91 to 1.22) 2.14 (1.51 to 3.03) 1.08 (0.99 to 1.18) 1.48 (0.87 to 2.52) 1.07 (0.92 to 1.25) Numbers are percentages unless otherwise stated. aRR, adjusted RR, comparing current drug use with no current drug use; CQ/HCQ, chloroquine/hydroxychloroquine; DMARD, disease- modifying antirheumatic drug; model 1, adjusted for all other drugs in the table and glucocorticoids; model 2, model 1 plus further adjusted for all other a priori confounders listed in table 2. DISCUSSION Exposure to current oral glucocorticoid therapy was associated with a 20% increased risk of infection. The magnitude of this increased risk was slightly higher than that seen with metho- trexate. This risk can be expressed as a number needed to harm, in which for every 13 patients treated with glucocorticoid ther- apy over a 1-year period (assuming a constant hazard), there was one additional NSI. Whereas the risk appeared greater with any current oral glucocorticoid therapy compared with none, there was a dose–response relationship, and the risk was clearly greater at daily doses above 20 mg PEQ per day (aRR 1.85, 1.68 to 2.05). These results replicate the ﬁndings of another Canadian administrative database study, which found an aRR of 1.15 (1.11 to 1.19) for mild (ie, non-serious) infections comparing oral glucocorticoid therapy with no glucocorticoid or DMARD therapy.7 Allowing for some differences between the studies, this near-identical result adds weight to the observed associa- tion, although similar biases in the two studies cannot be ruled out. Many studies of serious infection exist, with RR estimates for all-site serious infection ranging from 1.5 to 2.5.6–10 Similar estimates exist for site-speciﬁc11 12 and organism-speciﬁc13 14 20 serious infection. Although the magnitude of RR is not as high with non-serious compared with serious infections, the baseline rate of NSI is much greater. This means that, despite the lower RR for NSI, the actual number of additional cases attributed to glucocorticoid therapy is greater for non-serious compared with serious infection. Ann Rheum Dis 2011;70:956–960. doi:10.1136/ard.2010.144741 The strengths of this study include its size. We were able to identify over 13 000 patients with an infection in a patient population of over 16 000 patients. Although this meant that individual subjects were selected more than once as controls, this is necessary within nested case–control analyses to avoid the introduction of bias.21 The administrative setting meant that there was no selection bias, as we were able to study the whole population over 65 years. Indeed, this older population is at higher background risk of infection and is of particular clinical interest. Limitations do exist in this administrative database study. Patients with RA were identiﬁed using billing codes, intro- ducing the possible misclassiﬁcation of patients with other musculoskeletal diseases. The additional requirement for a DMARD prescription should, however, minimise this problem. Glucocorticoid exposure was ascertained from dispensary data. Once dispensed, it is possible that patients were non-adherent. This could include patients not taking medication that was dis- pensed, or alternatively taking cached medication. Such patient decisions may be inﬂuenced by disease activity. Any resultant misclassiﬁcation of the exposure could be differential in either direction and could bias the result either towards or away from the null. We have considered the inﬂuence of only current glu- cocorticoid exposure upon the risk of NSI. Although more com- plex methods exist to model the relationship ﬂexibly between time-varying dose and outcome, our analysis methodology matches that of previous studies, thereby making the results more comparable. Furthermore, it makes biological sense that 959