LUPUS nephritis (LN) is a severe complication of systemic lupus erythematosus, requiring effective treatment strategies to manage renal involvement. The impact of glucocorticoid dosing on treatment outcomes, such as complete response (CR), serious infections, and mortality, is critical for optimizing patient care. A study that involved a systematic review and meta-analysis of randomized controlled trials (RCTs) that investigated these effects, providing insights into the balance between efficacy and safety of glucocorticoid regimens in LN treatment.
Researchers conducted a systematic review and meta-analysis of the control arms of RCTs involving patients with biopsy-proven LN. The included studies utilised glucocorticoids combined with mycophenolic acid analogues or cyclophosphamide. Key parameters, such as starting glucocorticoid dose, tapering methods, and the use of glucocorticoid pulses, were analysed. The outcomes were assessed at 6 and 12 months, including CR rates, serious infections, and mortality. The meta-analysis included proportions, meta-regression, and subgroup analyses to identify dose-response relationships. The analysis incorporated 50 RCT arms involving 3,231 patients with LN.
Results showed that starting on oral prednisone at 25mg/day without pulses predicted a CR rate of 19.5% (95% CI 7.3-31.5). Increasing the starting dose to 60mg /day without pulses improved CR rates to 34.6% (95% CI 16.9-52.3). The predicted rate of serious infections was 3.2% (95% CI 2.4–4.0) for a 25 mg/day dose, increasing to 12.1% (95% CI 9.3–14.9) with a 60 mg/day dose. Mortality rates were 0.2% (95% CI 0.0–0.4) for the lower dose and 2.7% (95% CI 0.0–5.3) for the higher dose. The addition of glucocorticoid pulses increased the rates of CR and mortality but did not significantly affect the rate of serious infections. A dose-response relationship was observed, showing higher initial glucocorticoid doses were associated with better renal outcomes but at the cost of increased risks of serious infections and death.
The study results show that higher doses of glucocorticoids during initial therapy improve renal response rates but significantly increase the risks of infections and mortality. These findings underscore the need for carefully tailored glucocorticoid regimens to maximize therapeutic benefits while minimizing adverse effects in LN management.
Aleksandra Zurowska, EMJ
Reference
Figueroa-Parra G et al. Impact of Glucocorticoid Dose on Complete Response, Serious Infections, and Mortality During the Initial Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis of the Control Arms of Randomized Controlled Trials. ACR. 2024. [Epub ahead of print].
