Systematic review and meta-analysis of the low-dose versus high-dose cyclophosphamide regimen for induction treatment in lupus nephritis patients, evidence update 2010–2023

Abstract

Introduction

Lupus nephritis is a common complication in patients with systemic lupus erythematosus. Cyclophosphamide in induction treatment has a good efficacy profile, but greater toxicity.

Objective

To perform a systematic review and meta-analysis, updating the literature that compares the efficacy and safety of cyclophosphamide at high and low doses.

Materials and methods

PRISMA-P methodology, PROSPERO register number CRD42023485477, only randomized clinical trials were included from 2010 to October 2023, in patients over 16 years of age with lupus nephritis class III, IV, V, or V + III, V + IV. Complete response, partial response, relapses, infections, leukopenia, and amenorrhoea were measured, the RR was estimated for a 95% CI, based on the Mantel-Haenszel method, and heterogeneity by I² and Q test.

Results

415 articles were found, only three were included with 406 patients, 217 for the high dose group and 189 low doses. There were no statistically significant differences with respect to complete response (RR = 0.77, 95% CI 0.60–1.01, p = 0.06), partial response (RR = 0.88, 95% CI 0.67–1.16, p = 0.35), relapses (RR = 2.16, 95% CI 0.18–24.7, p = 0.52) and infections (RR = 0.68, 95% CI 0.45–1.04, p = 0.08), while leukopenia and amenorrhoea were significantly uncommon in the low dose group (RR = 0.41, 95% CI 0.22–0.77, p = 0.01) and (RR = 0.40, 95% CI 0.25–0.64, p = 0.002).

Conclusions

The use of low-dose cyclophosphamide is as effective as the high-dose regimen and the probability of leukopenia and amenorrhoea is lower.