Low-Dose Mycophenolate Mofetil for Treatment of Neuromyelitis Optica Spectrum Disorders: A Prospective Multicenter Study in South China

Abstract

Objective: To evaluate the efficacy and safety of low-dose mycophenolate mofetil (MMF, 1,000 mg/day) treatment of neuromyelitis optica spectrum disorders (NMOSDs).Methods: This study was a multicenter, open, prospective, follow-up clinical trial. The data include retrospective clinical data from the pretreatment phase and prospective data from the post-treatment phase. From September 2014 to February 2017, NMOSD patients seropositive for aquaporin 4-IgG (AQP4-IgG) were treated with low-dose MMF.Results: Ninety NMOSD patients were treated with MMF for a median duration of 18 months (range 6–40 months). The median annual recurrence rate (ARR) decreased from 1.02 before treatment to 0 (P < 0.0001) after treatment, and the Expanded Disability Status Scale (EDSS) score decreased from 4 to 3 (P < 0.0001). The EDSS score was significantly lower (P = 0.038) after the first 90 days of treatment. The serum AQP4-IgG titer decreased in 50 cases (63%). The median Simple McGill pain score (SF-MPQ) was reduced in 65 patients (88%) with myelitis from 17 (range 0–35) to 11 (range 0–34) after treatment (P < 0.0001). The median Hauser walking index (Hauser Walk Rating Scale) was reduced from 2 (range 1–9) before treatment to 1 (range 0–7) after treatment (P < 0.0001). Adverse events were documented in 43% of the patients, and eight patients discontinued MMF due to intolerable adverse events. Fourteen (16%) of the total patients discontinued MMF after our last follow-up for various reasons and switched to azathioprine or rituximab.Conclusion: Low-dose MMF reduced clinical relapse and disability in NMOSD patients in South China. However, some patients still suffered from adverse events at this dosage.Clinical Trial Registration: www.ClinicalTrials.gov, identifier : NCT02809079.

Efficacy and Safety of Mycophenolate Mofetil Therapy in Neuromyelitis Optica Spectrum Disorders: A Systematic Review and Meta-Analysis

“…In addition, MMF has been substituted when treatment with AZA showed suboptimal responses or patients cannot tolerate the side effects of AZA. [24,22] Huang et al compared the e cacy and safety of MMF with RTX, AZA, CYP, and cyclosporine A (CyA) and found that MMF was superior to AZA and CYP but inferior to RTX and CyA. However, MMF had the highest tolerability among all IS in the study.…”

“…The proportion of steroid use ranged from 0% [21] to 100% [16,22,23]. In four studies [16,22,23,18], 177 patients (22.2%) had been taking oral corticosteroid at the time of MMF treatment. Two studies [21,24] were conducted with 160 patients (20.0%) who did not receive corticosteroid during MMF treatment.…”

“…The e cacy of MMF treatment determined by changes in ARR and EDSS is shown in Table 2. The median follow-up duration ranged from 13.5 months [22] to 95 months [21], with less than 24 months in 8 studies and 24 months or more in 7 studies. ( Table 1) [24,16,13,19] reporting ARR and 3 studies [24,16,13] reporting EDSS reported values by mean and SD, and therefore were included in the meta-analysis.…”

Efficacy and safety of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis

“…The efficacy of MMF treatment determined by changes in ARR and EDSS is shown in Table 2. The median follow-up duration ranged from 13.5 25 to 95 months 24 , with less than 24 months in 8 studies and 24 months or more in 7 studies ( Table 1). All studies gave neither detail of the MRI findings nor evaluated it as a treatment outcome.…”

Current immunotherapies for multiple sclerosis and neuromyelitis optica spectrum disorders: the similarities and differences

“…Anti-CD20, attacks B-cells and plasmoblasts NMOSD [159] , RRMS [160,161] , PPMS [162] Azathioprine 2-3 mg/(kg•day) , po Inhibits purine nucleotide synthesis; activates mitochondrial apoptotic pathway; activated T-cell apoptosis [163,164] NMOSD [159,165,166] , RRMS [167] Mycophenolate mofetil CellCept 1000-3000 mg/day, po Blocks guanine nucleotide production; inhibits lymphocyte proliferation [168,169] NMOSD [170][171][172] DMD: disease-modifying drug; IFN: interferon; sc: subcutaneous; iv: intravenous; im: intramuscular; po: per os; RRMS: relapsingremitting multiple sclerosis; SPMS: secondary progressive multiple sclerosis; PPMS: primary progressive multiple sclerosis; MHC: major histocompatibility complex; NMOSD: neuromyelitis optica spectrum disorders 14 mg, 20.2% DMF [135] Placebo, GA and mycophenolate mofetil, and is probably the best choice at present [184][185][186][187] . Rituximab is a human-mouse chimeric monoclonal antibody against CD20, which is a regulatory factor for the early activation and differentiation of B-cells.…”