Comparative efficacy and safety of mizoribine and mycophenolate mofetil for treating systemic lupus erythematosus: a retrospective cohort study

Abstract

Background: Mizoribine (MZR) is an immunosuppressive agent that selectively inhibits inosine monophosphate dehydrogenase; its actions are considerably similar to those of mycophenolate mofetil (MMF). This study aimed to clarify whether MZR can be a good treatment option for systemic lupus erythematosus (SLE) and to compare the efficacy and safety of MZR and MMF in patients with active SLE.

Methods: We retrospectively compared the efficacy, continuation rate, and safety of MZR (52 patients) and MMF (31 patients) after adjusting for stabilized inverse probability of treatment weighting based on propensity scores. The efficacy endpoints were as follows: cumulative incidence of lupus low disease activity state (LLDAS) or remission attainment and flares and change in prednisolone dose over 2 years. Drug continuation rates were defined as the time from drug initiation to discontinuation for any cause, owing to the lack of efficacy, or owing to adverse events. The safety endpoint was the frequency of adverse events.

Results: Overall, 25 (48.1%) and 13 (25.0%) patients in the MZR group and 18 (58.1%) and 15 (48.3%) in the MMF group achieved LLDAS and remission during the follow-up period, respectively; thus, the cumulative incidence of LLDAS and remission attainment of the two groups was similar after adjustment. Prednisolone dose was steadily reduced in both the groups, and the change in prednisolone dose was nearly identical between the two groups. Drug discontinuation rate due to adverse events and the frequency of all adverse events and infections were higher in the MMF group than in the MZR group, albeit without significance after adjustment.

Conclusion: MZR is as effective as MMF in controlling SLE activity. The adverse events of MZR, whose profile differs from MMF, are comparable to or less than those of MMF. MZR may be a valuable option as an immunosuppressive agent for SLE, as well as MMF.

Keywords: continuation rate; lupus low disease activity; mizoribine; mycophenolate mofetil; systemic lupus erythematosus.

Figure 1.

Algorithm for the inclusion and exclusion of the study population.

Figure 2.

The cumulative incidence of (a) LLDAS attainment, (b) remission attainment, and (c) flares in the MZR and MMF groups after adjusting for propensity score-based stabilized IPTW. CI, confidence interval; SHR, sub-distribution hazard ratio.

Figure 3.

Predicted changes in prednisolone dose in the MZR and MMF groups. Data and error bars represent means and 95% confidence intervals.

Figure 4.

(a) Drug continuation rates, (b) drug discontinuation rates due to the lack of efficacy, and (c) drug discontinuation rates due to adverse events in the MZR and MMF groups after adjusting for propensity score-based stabilized IPTW. CI, confidence interval; HR, hazard ratio.

Figure 5.

(a) The cumulative incidence of LLDAS attainment, (b) drug discontinuation rates due to the lack of efficacy, and (c) drug discontinuation rates due to adverse events in the MZR and MMF groups after adjusting for propensity score-based stabilized IPTW. The analysis was limited to moderately to severely active patients with a SLEDAI score of ⩾ 6. CI, confidence interval; HR, hazard ratio; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index 2000; SHR, sub-distribution hazard ratio.

Figure 6.

(a) The cumulative incidence of LLDAS attainment, (b) drug discontinuation rates due to the lack of efficacy, and (c) drug discontinuation rates due to adverse events in the MZR and MMF groups after adjusting for propensity score-based stabilized IPTW. The analysis was limited to patients who received no concomitant calcineurin inhibitors. CI, confidence interval; HR, hazard ratio; SHR, sub-distribution hazard ratio.