Rituximab Superior in Reducing Relapse Risk for NMOSD Patients


The risk of relapse was higher with treatment of mycophenolate mofetil in patients with neuromyelitis optica spectrum disorder and other first-line immunosuppressants, compared to treatment with rituximab.

Romain Marignier, MD, PhD

Romain Marignier, MD, PhD

Results from a study of patients with neuromyelitis optica spectrum disorder (NMOSD) suggest that first-line treatment with rituximab is more effective in suppressing clinical activity, independent of the antibody status, compared with mycophenolate mofetil (MMF) and other first-line immunosuppressants. Notably, this study provides Class III evidence that rituximab is superior to MMF to reduce the risk of relapse in patients with NMOSD.

The NOMADMUS study group researchers, including Hélène Zephir, MD, PhD, found a higher risk of relapse among MMF-treated patients than those treated with rituximab (hazard ratio [HR], 2.74; 95% CI, 1.17—6.40; P = .020) after adjusting for age at disease onset, sex, antibody status, disease duration, adjusted relapse rate (ARR) before treatment, corticosteroid, and relapse location.

The multicenter, retrospective cohort study included a total of 136 patients with NMOSD whose disease onset ranged from April 1993 to May 2017. Patients included in the study had a diagnosis of NMOSD according to the Wingerchuk 2015 criteria and positive for anti-AQP4 or anti-MOG antibodies, initiation of immunosuppressive treatment as a first-line therapy within 3 years after disease onset, and at least 1-year follow-up (whether the treatment was stopped or not).

Those excluded from the study included patients with seronegative NMOSD and those who previously received immunosuppressive therapies that are specifically used for multiple sclerosis (MS).

Medical records such as date of disease onset (first attack), initiation of the first-line immunosuppressive treatment, end of follow-up or withdrawal of treatment, demographic variables, serologic status, reasons for stopping, and serious infectious events (SIEs) were all recorded. Researchers used defined attack and relapse as new central nervous system symptoms, as well as disease onset defined as the first neuromyelitis optica (NMO) relapse.

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The occurrence of relapse after initiating the first-line immunosuppressive treatment was measured as the primary outcome, while ARR was measured as the secondary outcome. ARR was calculated from the initiation of the first-line immunosuppressive treatment to the end of follow-up or withdrawal of treatment. Additional safety outcomes such as SIEs were recorded and defined as an infection requiring hospitalization, injectable anti-infective therapy, or leading to death.

Among the 136 patients with NMOSD included in the study, 62 (45.6%) were treated with rituximab, 42 (30.9%) with MMF, 23 (16.9%) with azathioprine, 6 (4.4%) with cyclophosphamide, and 3 (2.2%) with mitoxantrone.

The 1-year and 3-year proportions of relapse free patients treated with rituximab, MMF, and azathioprine were 85.5% (95% CI, 79.6—92) and 72.2% (95% CI, 63.9–81.6%), respectively. While the risk of relapse was significantly higher among MMF-treated patients, there was no significant difference between rituximab-treated patients and azathioprine-treated patients (HR, 2.13; 95% CI, 0.72–6.28; P = .17).

Overall, ARR before treatment (excluding the first relapse) was higher than ARR after treatment (0.91 [95% CI, 0.69—1.19] vs 0.18 [95% CI, 0.12–0.27]; P <.001) for the whole population.

Among those treated with rituximab, 1 SIE were present in 5 of the 62 patients and 1 patient presented 2 SIEs during the follow-up (3 bacteremia, 2 pneumonia, and 1 urinary tract infection). Additionally, 5 of the 42 MMF-treated patients had at least 1 SIE, 2 presented with 2 SIEs and 1 presented with 3 SIEs (6 urinary tract infections, 2 pneumonia, 1 cellulitis). Researchers found no SIEs in patients treated with azathioprine, cyclophosphamide, or mitoxantrone.

“The results of this French multicenter, retrospective cohort study suggest that (1) the initiation of any first-line immunosuppressive therapy was associated with a decrease in clinical activity of the disease, (2) the risk of relapse for MMF-treated patients is significantly higher than that for patients treated with RTX, independent of serologic status, and (3) RTX was not associated with a higher risk of serious infection compared with MMF,” the Zephir et al. concluded.


Poupart J, Gioivannelli J, Deschamps R, et al. Evaluation of efficacy and tolerability of first-line therapies in NMOSD. Neurology. 2020;94:1-12. doi:10.1212/WNL.0000000000009245.

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