Mycophenolate Mofetil in the Treatment of Neuromyelitis Optica Spectrum Disorder

Abstract

IMPORTANCE Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disorder of the central nervous system. Recently, various immunosuppressant medications were introduced as therapeutic options for preventing relapse of NMOSD. However, our understanding of the effectiveness of mycophenolate mofetil (MMF) in treating patients with NMOSD is based on only a small number of studies.OBJECTIVE To evaluate the efficacy and safety of MMF treatment in patients with NMOSD. DESIGN, SETTING, AND PARTICIPANTSA 3-center retrospective review of our experiences, examining results from 59 patients with NMOSD (24 with neuromyelitis optica and 35 with a limited form of the disease) who were treated with MMF (1000-2000 mg/d). MAIN OUTCOMES AND MEASURESPatients' annualized relapse rate, disability as measured by the Expanded Disability Status Scale, and experience of adverse effects due to MMF were assessed. RESULTSOf the 59 patients, 1 with NMOSD who had to discontinue MMF use in the first month due to a rash was excluded. The remaining 58 patients were included in the drug-efficacy analysis. The median post-MMF annualized relapse rate was significantly lower than the pre-MMF annualized relapse rate (0.0 vs 1.5; P < .001). The Expanded Disability Status Scale scores also significantly decreased after MMF treatment (3.0 vs 2.5; P = .005). Thirty-five patients (60%) were relapse free, and Expanded Disability Status Scale scores were stabilized or improved in 53 patients (91%). Fourteen patients discontinued MMF treatment owing to ongoing relapse (10 patients), rash (1 patient), pregnancy (1 patient), and financial problems (2 patients), but MMF was generally well tolerated. CONCLUSIONS AND RELEVANCEIn this observational study, MMF treatment induced reduction of relapse frequency, stabilized or improved disability, and was well tolerated in patients with NMOSD.

Long-term Therapy With Interleukin 6 Receptor Blockade in Highly Active Neuromyelitis Optica Spectrum Disorder

“…While therapeutic interventions with immunosuppressive drugs can reduce the frequency of NMO relapses, 3,[7][8][9][10][11] individual patients in most studies did not respond sufficiently to treatment or experienced major adverse effects. Therefore, better preventive NMO therapies are desirable.…”

“…3 However, relapse prevention remains a challenging issue in NMO because established multiple sclerosis therapies such as interferons, natalizumab, and fingolimod have been reported to show little efficacy or even to be detrimental. [4][5][6] According to smaller case series or retrospective cohort studies, long-term immunosuppression with azathioprine 7 or mycophenolate mofetil 8 is recommended for mild NMO cases, with methotrexate being an alternative treatment option. 3,9 In patients with more severe NMO courses, rituximab 10 and mitoxantrone hydrochoride 11 have been reported to diminish the relapse frequency.…”

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

“…Theoretically, the absence of attack-related inflammation could also release repair processes such as remyelination. Indeed, several studies investigating broad or selective immunosuppression reported an improvement of disability during the course of treatment [21,81,83,84,87,92,102,121,122].…”

“…It inhibits lymphocyte proliferation by suppression of guanosine nucleotide biosynthesis and is used for psoriasis, proliferative lupus nephritis, and renal transplant rejection. Four retrospective cohorts evaluating 24-58 patients with mostly AQP4-IgG-positive NMOSD have reported beneficial outcomes of MMF therapy with or without concomitant corticosteroids [79,81,83,84]. MMF treatment for a median of 20-27 months resulted in a reduction of the ARR by 80-93 % and improvement of the median EDSS in 3/ 4 studies (not reported in 1).…”

“…MMF treatment for a median of 20-27 months resulted in a reduction of the ARR by 80-93 % and improvement of the median EDSS in 3/ 4 studies (not reported in 1). More than 90 % of patients had stable or improved disability [83,84], and 46-65 % were relapse-free [79,81,83,84]. Discontinuation rates due to disease activity or side effects were 15-25 %.…”