Rituximab may not be safe to use in patients with neuromyelitis optica spectrum disorder (NMOSD), according to an article recently published in Neurology, Neuroimmunology & Neuroinflammation.

“Patients with prolonged memory B-cell depletion after [rituximab], previous mitoxantrone history, [hypogammaglobulinemia (hypo-IgG)] at baseline, or obesity were at risk of developing [rituximab]-induced hypogammaglobulinemia,” the authors wrote.

A retrospective study was conducted including 169 patients previously diagnosed with NMOSD who received 1 to 27 courses of rituximab (median of 10) for at least 1 year. The longest treatment was over 15 years, with a median duration of 8 years.

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Up to 41% of the patients showcased hypo-IgG during treatment, while 34% had a total of 114 infections, out of which 8% were cataloged as severe infections. Urinary tract infection was the most common cause, followed by respiratory tract infections, herpes, and others.

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The mean dose of rituximab received in a year and overall years of treatment duration appeared to be an independent predictor of hypo-IgG, and the study suggests relapses during treatment with this drug may increase the risk of acquiring infections.

Other factors associated with hypo-IgG included a history of mitoxantrone use, body mass index of 25 kg/m2 or less, and, unsurprisingly, low baseline IgG values. As for the risk of infection, the only other related item was the score on the Expanded Disability Status Scale.

Importantly, infection rates generally were as expected in the course of the treatment and did not exhibit an independent association with suboptimal values of IgG.

Rituximab is a monoclonal antibody frequently used in proinflammatory diseases in the central nervous system such as NMOSD due to its ability to deplete B cells that express the CD20 marker. Concerns about the safety of this drug have arisen in the past, especially regarding the adverse effects the long treatment may have.

“Further studies are necessary to evaluate the clinical effect of more severe and prolonged hypogammaglobulinemia in patients with NMOSD and to identify high-risk patients for developing symptomatic hypogammaglobulinemia,” the authors concluded.


Kim S, Park N, Kim K, Hyun J, Kim H. Rituximab-induced hypogammaglobulinemia and risk of infection in neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm. Published online July 19, 2022. doi:10.1212/nxi.0000000000001179