Rituximab-Induced Hypogammaglobulinemia and Infection Risk in Multiple Sclerosis

Reduced immunoglobulin G (IgG) levels were reported for almost a quarter of patients with multiple sclerosis (MS) treated with rituximab with a potential interaction between IgG level and the risk for infection, according to study findings published in Neurology Neuroimmunology & Neuroinflammation.

The objective of the current study was to investigate the incidence of hypogammaglobulinemia and infections in patients with MS who were treated with rituximab in the MS center of Marseille, France.

The prospective, observational study included 188 patients (mean age, 43.4 years; 118 women) with MS who were treated with rituximab. The median follow-up after the first rituximab infusion was 3.5 years (range 1–5.8 years), and the median number of rituximab infusions was 5 (range 1–9 infusions).

Reduced levels of IgG <6 g/L were documented in 14 patients (7.4%) before the first infusion of rituximab and in 44 patients (23.4%) after treatment initiation.

After the first rituximab infusion, 133 of 188 patients (70.8%) had symptomatic infections (5.9%) and 11 of 188 patients (5.9%) had 13 severe infections. After 4 years, 24.4% of patients (95% CI 18.0–33.1) were free of any infection and 92.0% (95% CI 87.1–97.1) had not experienced a severe infection.

There was a clear association between IgG levels with risk for infection, as high IgG level was associated with a 14% decreased risk for infection (hazard ratio, 0.86; 95% CI, 0.75-0.98; P =.029), with no predictive value of age, expanded disability status scale, or interaction.

The risk of reduced IgG level <6 g/L increased with age (hazard ratio, 1.36, 95% CI 1.06–1.75; P =.016) but was not associated with sex or history of immunosuppressive treatment.

Study limitations included the observational design, lack of a control group, and short observation time.

“[T]he present findings highlight the need to regularly monitor Ig levels in PwMS [patients with multiple sclerosis] receiving B-cell depleting therapy to potentially reduce the risk of infection,” concluded the researchers.


Perriguey M, Maarouf A, Stellmann JP, et al. Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with rituximab. Neurol Neuroimmunol Neuroinflamm. Published online, November 23, 2021. doi: 10.1212/NXI.0000000000001115