Low Dosage and Long-Term Use of Cyclophosphamide Improve the Survival of Patients with Systemic Lupus Erythematosus

Abstract Background: Cyclophosphamide (CTX) is an alkylating agent used in the treatment of systemic lupus erythematosus (SLE) for its potent immunosuppression effect. Many aspects of the use of CTX in SLE have been previously studied. However, its relation to mortality in SLE had rarely been mentioned. Thus we investigate the effect of cyclophosphamide on organ involvements and the overall and cause-specific mortality of SLE patients. Methods: Information about CTX prescription were taken from medical records in the Jiangsu Lupus database that was set up to collect data from SLE patients since their first admission during 1999-2009 in Jiangsu province, China. Follow- up studies were carried out in 2010 and 2015 to check the survival status of the patients. Cox regression models were used to estimate hazard ratio (HR) and 95% CI. Kaplan-Meier model was used to assess the effect of CTX on mortality between organ involvements and non-involvements. Results: There were 221 deaths observed out of 2446 SLE patients. CTX users showed a lower mortality of SLE (8.4%) with adjusted HR (95% CI) of 0.74 (0.56-0.97), as compared to non-users. A decreased in overall mortality of SLE in low daily dosage of CTX, with adjusted HR (95% CI) of 0.54 (0.36-0.81) and a significant dose-response pattern ( P = 0.004) between overall mortality of SLE and long-term use of CTX with adjusted HR (95% CI) 0.53 (0.35-0.80) were observed. In cause-specific mortality analyses, protective effective of CTX was found to be insignificant. However, CTX could eliminate the differences in mortality between organ involvement and non-involvement, including renal, neuropsychiatric, cardiopulmonary, gastrointestinal and hematological involvements. Conclusion: Low daily dosage and long-term use of CTX lowers the risk of overall mortality of SLE. CTX might improve the survival of patients with renal, neuropsychiatric, cardiopulmonary, gastrointestinal and hematological involvements.