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Importance Despite the increased use of rituximab therapy in neuromyelitis optica spectrum disorder (NMOSD), the overall efficacy and safety of long-term rituximab treatment in a large group of patients is uncertain. Furthermore, the identification of a predictor of rituximab response is an important issue for assessing the individual risk-benefit of therapy and making treatment decisions. Objective To assess the long-term clinical efficacy and safety of rituximab treatment in patients with NMOSD and the influence of fragment c gamma receptor 3A ( FCGR3A ) polymorphisms on rituximab response. Design, Setting, and Participants A retrospective review of 100 patients with relapsing NMOSD treated with rituximab for at least 6 months, from February 1, 2006, to January 31, 2015, at the institutional referral center. After induction therapy, a single infusion of rituximab (375 mg/m 2 ) as maintenance therapy was administered whenever a reemergence of CD27 + memory B cells among peripheral blood mononuclear cells occurred. Using an allele-specific polymerase chain reaction–based method, the gene polymorphisms FCGR3A -V158F were assessed. Main Outcomes and Measures The primary end point was annualized relapse rate; disability (Expanded Disability Status Scale score), safety of rituximab treatment, event of insufficient memory B-cell depletion following rituximab, and time to retreatment of rituximab were secondary end points. Results By January 31, 2015, a total of 100 patients received repeated rituximab treatment during a median of 67 months. Of these patients, 41 had more than 5 years’ follow-up and 24 had more than 7 years’ follow-up. The annualized relapse rate was reduced significantly by 96% (mean [SD] annualized relapse rate of prerituximab vs postrituximab, 2.4 [2.0] vs 0.1 [0.6]) and disability improved or stabilized in 96% of patients. Rates of adverse events were generally stable. The FCGR3A -F allele was associated with a risk of relapse while receiving rituximab treatment (additive model, P P = .04; maximum, P = .03) and insufficient memory B-cell depletion (additive model, P = .03; recessive model, P = .03; maximum, P = .03). Conclusions and Relevance Repeated rituximab treatment for NMOSD was observed in an increasing number of patients and increasing duration of exposure and maintained good efficacy and a safety profile consistent with previous reports. The finding of a relationship between FCGR3A genetic polymorphisms and rituximab response suggests the importance of individualized rituximab treatment strategies in NMOSD.

This study examines the safety and efficacy of bortezomib in patients with highly relapsing neuromyelitis optica spectrum disorder.

Importance IgG4-related disease, which is newly recognized, is characterized by lymphoplasmacytic infiltration with increased IgG4-secreting plasma cells. Although a favorable response to steroids has previously been reported, the durations of follow-up to confirm the long-term benefits and clinical courses were limited. We describe long-term favorable response of oral methotrexate in a patient with IgG4-related pachymeningitis who was resistant to steroid therapy. Observations A patient in his mid-60s with pathologically proven IgG4-related pachymeningitis who was resistant to steroid therapy and experienced an exacerbation of symptoms 4 times is described. Low-dose oral methotrexate induced significant clinical and radiological improvement, with sustained remission of the disease over 2 years without complications. Conclusions and Relevance The long-term favorable response to oral methotrexate in the current patient suggests that methotrexate is a useful alternative treatment option in patients with IgG4-related pachymeningitis who are resistant to steroid therapy or who experience adverse effects from steroids.

Importance A previous 2-year analysis of repeated rituximab treatment in patients with neuromyelitis optica (NMO) revealed significant improvements in relapse rates and disability. We report the findings from the longest follow-up of rituximab treatment in NMO, which provide reassurance regarding the long-term efficacy and safety of rituximab in NMO. Objective To report the results of rituximab treatment in patients with relapsing NMO or NMO spectrum disorder (NMOSD) for a median of 60 months. Design, Setting, and Participants Retrospective case series in an institutional referral center for multiple sclerosis, including 30 patients with relapsing NMO or NMOSD. Interventions After induction therapy, a single infusion of rituximab (375 mg/m 2 ) as maintenance therapy was administered whenever the frequency of reemerging CD27 + memory B cells in peripheral blood mononuclear cells, as measured with flow cytometry, exceeded 0.05% in the first 2 years and 0.1% thereafter. Main Outcomes and Measures Annualized relapse rate (ARR), disability (Expanded Disability Status Scale score), change in anti–aquaporin 4 antibody, and safety of rituximab treatment. Results Of 30 patients, 26 (87%) exhibited a marked reduction in ARR over 5 years (mean [SD] pretreatment vs posttreatment ARR, 2.4 [1.5] vs 0.3 [1.0]). Eighteen patients (60%) became relapse free after rituximab treatment. In 28 patients (93%), the disability was either improved or stabilized after rituximab treatment. No serious adverse events leading to discontinuation were observed during follow-up. Conclusions and Relevance Repeated treatment with rituximab in patients with NMOSD over a 5-period, using an individualized dosing schedule according to the frequency of reemerging CD27 + memory B cells, leads to a sustained clinical response with no new adverse events.

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.To evaluate the efficacy and safety of MMF treatment in patients with NMOSD.A 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).Patients' annualized relapse rate, disability as measured by the Expanded Disability Status Scale, and experience of adverse effects due to MMF were assessed.Of 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.In this observational study, MMF treatment induced reduction of relapse frequency, stabilized or improved disability, and was well tolerated in patients with NMOSD.