Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide

Background. Long-term intravenous cyclophosphamide (IVC) in combination wit h corticosteroids is standard therapy for proliferative lupus nephritis, bu t it has limitations. There are few data on long-term remission rates, pred ictors of relapse, and the ability to achieve a second remission with curre ntly recommended IVC regimens. Methods. A cohort of 85 patients with proliferative lupus glomerulonephriti s (focal N = 33, diffuse N = 52) treated with IVC was assembled in three in stitutions. Timing and predictors of remission, relapse, and re-remission w ere evaluated with Kaplan-Meier analyses and Cox models. Results. The median time to remission was 10 months, whereas an estimated 2 2% of patients had not remitted after 2 years. The median time to relapse a mong 63 patients who had achieved remission was 79 months. In multivariate models, adverse predictors of remission were a delay in the initiation of t herapy from the time nephritis was clinically diagnosed [hazard ratio (HR) 0.58, P = 0.063] and a higher amount of proteinuria (HR 0.86 per 1 g/24 hou rs, P = 0.014). Predictors of earlier relapse for patients entering remissi on included a longer time to remission (HR 1.029 per month, P = 0.025), a h istory of central nervous system involvement (HR 8.41, P = 0.002), and Worl d Health Organization histology (P = 0.01). Among the 23 patients who relap sed during follow-up, the median time to re-remission was 32 months, and wi th three exceptions, all patients took substantially longer time to remit t he second time compared with their first remission (P = 0.01). The time to re-remission was longer in patients who had taken longer to remit the first time (HR 0.979 per month, P = 0.16), in patients who had relapsed earlier after the first remission (HR 1.071 per month, P = 0.002), and in those wit h evidence of chronicity in the original kidney biopsy (P = 0.015). Conclusions. Prolonged courses with a cumulative risk of toxicity are neede d to achieve remission in many first-treated patients and in most patients treated for a second time. The optimal management of patients with identifi ed adverse predictors of response needs further study.