Association of CYP2C19 polymorphism with cyclophosphamide-induced toxicity in systemic lupus erythematosus and lupus nephritis: A systematic review and meta-analysis

Abstract

Background

Cyclophosphamide (CYC) is a key immunosuppressive agent used for the treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN). However, its use is often limited by variability in efficacy and toxicity, potentially influenced by genetic polymorphisms. This systematic review and meta-analysis aimed to evaluate the association between the CYP2C19 polymorphism and cyclophosphamide-induced toxicity in SLE and LN patients.

Methods

Literature search was performed using PubMed and Web of Science databases in accordance with PRISMA guidelines. Studies were included if they evaluated cyclophosphamide therapy in SLE or LN patients, assessed genetic polymorphisms, and reported toxicity outcomes. Meta-analysis was performed using inverse variance weighted fixed effect and random effect, publication bias was checked using funnel plot and risk of bias was assessed using ROBINS E tool.

Results

Out of 1,713 identified articles, a total of 5 studies were eligible for meta-analysis which studied CYP2C19*2 genetic Polymorphism and CYC induced toxicity. It showed a significant association with protective effect (OR = 0.28, 95% CI: 0.099–0.845, p = .021). Funnel plots suggested potential publication bias in CYP2C19*2 studies, while the risk of bias assessment revealed some concerns regarding confounding and outcome measurement.

Discussion

This meta-analysis supports the utility of CYP2C19*2 genotyping in predicting CYC induced toxicity in SLE and LN patients. Small sample sizes, confounding factors, and variability in outcome assessment were found to be the key limitations. Larger, multi ethnic studies with standardized toxicity assessments are recommended to validate these findings and explore these pharmacogenetic markers for optimizing CYC therapy.