JAMA: Oral mizoribine with glucocorticoids safe and effective for treatment initiation in lupus nephritis

A new study published in the Journal of American Medical Association showed that when taken with glucocorticoids for induction treatment of active lupus nephritis, oral mizoribine was well tolerated and noninferior to intravenous cyclophosphamide.

Intravenous cyclophosphamide is commonly used to treat lupus nephritis, however it has significant side effects. An option to induction treatment for lupus nephritis might be oral mizoribine. There are not many extensive, long-term clinical trials with mizoribine, though. Thus, to evaluate the safety and effectiveness of oral mizoribine against IV cyclophosphamide as induction treatment for Chinese patients with lupus nephritis, Zheyi Dong and colleagues carried out this investigation.

The patients with class III, III+V, IV, IV+V, or V lupus nephritis between the ages of 18 and 70 were recruited from 40 Chinese facilities for this clinical study. A 24-hour urine protein level of 1.0 g or more and a systemic lupus erythematosus disease activity index of 8 or higher were prerequisites for inclusion. The trial concluded on March 14, 2019, with the first patient being enrolled on November 29, 2014. 52 weeks was the follow-up period.

Analysis of the data took place between September 4, 2019, and January 21, 2020. For 52 weeks, oral glucocorticoids were administered together with oral mizoribine (50 mg, three times a day) or cyclophosphamide (6 intravenous doses at 0.5-1.0 g/m2 body surface area, with a maximum dosage of 1.0 g/d).

A total of 250 patients in all were randomized, and 243 of them received treatment (120 patients [49.4%] received cyclophosphamide, and 123 patients [50.6%] received mizoribine). The relative risk ratio (mizoribine vs. cyclophosphamide) was 0.861, and the overall remission rate at 52 weeks was 66.1% (76 of 115 patients) for the mizoribine group and 76.8% (86 of 112 patients) for the cyclophosphamide group.

Mizoribine was not inferior to cyclophosphamide, as shown by the 2-sided 95% CI's lower limit being higher than the noninferiority margin of 0.726. Kidney function and other immunological parameter changes were mostly comparable among the groups.

Upper respiratory tract infections were the most common adverse event in both groups, with the frequency of any treatment-related treatment-emergent adverse events being 80.5% in the mizoribine group and 78.7% in the cyclophosphamide group. Overall, this study found that induction treatment with oral mizoribine in conjunction with glucocorticoids seems to be both safe and effective for Chinese patients with lupus nephritis.

Reference:

Dong, Z., Luo, P., Sun, S., Ni, Z., He, Y., Huang, X., Liu, Z., Wu, Z., Zhang, X., Liao, Y., Zhao, J., Lin, H., Zhang, X., Fu, R., Ding, G., Xu, Y., Wang, L., Xiao, Y., Shi, S., … Chen, X. (2025). Mizoribine or cyclophosphamide for lupus nephritis: A randomized clinical trial. JAMA Network Open, 8(3), e250648. https://doi.org/10.1001/jamanetworkopen.2025.0648