Background Arguments against glucocorticoid (GC) use are dominated by fear of adverse effects, mainly based on experience with long-term and/or high-dose GC. Whether this concern is relevant for the lengths of treatment and doses in the EULAR recommendations for GC therapy in RA (1) remains to be clarified.
Objectives To assess: the risk of adverse effects of GC therapy in randomized controlled trials (RCTs) of GC in RA; the risk of Adverse Events (AE)-associated withdrawals; and withdrawal due to any cause.
Methods A systematic literature search followed by evidence synthesis and meta-analysis of RCTs, where the compared interventions included any difference in GC dosing, independent of type of administration, type of GC, or study duration. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. The quality of the evidence (a measure of confidence in the estimates) was assessed as recommended by the GRADE Working Group (2). Outcomes comprised those found most worrisome by EULAR Rheumatologists and patients (3).
Results Of 2821 references identified 524 were reviewed in detail and 59 (66 randomized comparisons with a total of 4831 patients) were found eligible for inclusion. Median study duration: 24 weeks (range: 1-104); median prednisone equivalent dose difference (more vs. less) of 6.2 mg/day (IQ range 2.0 -13.9). The empirical evidence suggests, with varying confidence in the estimates, that the risks of the most worrisome adverse effects are not increased (Table). Renal dysfunction was increased; however confidence in the estimate was low due to (i) few incidences observed (the number of patients did not reach the optimal information size) and (ii) the indirectness as some studies used concomitant cyclosporine therapy.
Conclusions This meta-analysis of trials does not support the notion of an increased risk for a wide range of side effects traditionally associated GC, when the GC is used at low to moderate doses over a median of 24 weeks. Patients receiving more GC were less likely to withdraw from studies compared to controls.
Acknowledgements This study was supported by a grant from Danish Medicines Agency, MundiPharma, and unrestricted grants from The Oak Foundation.
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Disclosure of Interest S. Tarp Grant/Research support from: MundiPharma, E. Bartels Grant/Research support from: Mundipharma, J. Kirwan Grant/Research support from: Nitec, Mundipharma, Horizon, D. Furst Grant/Research support from: NItec,Pfizer, M. Boers Grant/Research support from: Nitec, MundiPharma, Horizon, T. Woodworth: None Declared, H. Bliddal Grant/Research support from: MundiPharma, B. Danneskiold-Samsøe: None Declared, L. Kristensen Grant/Research support from: NorPharma, S. Thirstrup: None Declared, M. Rasmussen: None Declared, R. Christensen Grant/Research support from: MundiPharma