Insufficient mycophenolate mofetil maintenance dosage increases the relapse risk in neuromyelitis optica spectrum...

The utilization of biologic agents for neuromyelitis optica spectrum disorders (NMOSD) is constrained by high cost and limited accessibility in China. While clinical guidelines recommend mycophenolate mofetil (MMF) for relapse prevention, the factors influencing its therapeutic efficacy remain poorly characterized. This study aimed to investigate clinical predictors of relapse in patients with NMOSD treated with MMF, specifically evaluating the impact of MMF maintenance dosage and concurrent corticosteroid therapy on relapse prevention.

In this retrospective cohort study, clinical data were collected from NMOSD patients consecutively treated with MMF at the Departments of Neurology of the First Affiliated Hospital of Soochow University and the Second Affiliated Hospital of Anhui Medical University. Patients were categorized into three groups based on their maintenance dosage: low-dose (≤ 750 mg/d), medium-dose (= 1000 mg/d), and high-dose (≥ 1250 mg/d). The primary endpoint was the first relapse during treatment. Kaplan-Meier analysis was employed to compare relapse-free survival rates among groups, and Cox proportional hazards regression models were utilized to identify factors associated with relapse during follow-up.

A total of 82 NMOSD patients were included (34 males and 48 females), with a mean age of 43.6 ± 15.9 years. During the median follow-up time of 27.7 months, 39 patients (47.6%) experienced relapse. Kaplan-Meier analysis demonstrated that the relapse-free survival rate in the high-dose group was significantly higher than that in the medium-dose group and the low-dose group (log-rank test, p = 0.003). Additionally, concurrent corticosteroid use was linked to a reduced risk of relapse (p = 0.008, log-rank test). Multivariate Cox proportional hazards regression analysis indicated that compared with the high-dose group, patients in the medium-dose group (HR = 4.724, 95% CI: 1.537-14.522, p = 0.007) and low-dose group (HR = 4.758, 95% CI: 1.631-13.878, p = 0.004), as well as those who had previously received other conventional immunosuppressants (HR = 2.057, 95% CI: 1.038-4.073, p = 0.039), had a significantly increased risk of relapse. Conversely, concurrent corticosteroid use (HR = 0.417, 95% CI: 0.207-0.840, p = 0.014) emerged as a protective factor against relapse.

Suboptimal MMF maintenance dosing (≤ 1000 mg/d) significantly increases the risk of relapse in patients with NMOSD. A high-dose regimen (≥ 1250 mg/d) and concurrent corticosteroid administration, if well-tolerated, represent key strategies to mitigate relapse risk during MMF treatment.