In individuals with an autoimmune disease, such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and hypogammaglobulinemia, treatment with rituximab is associated with risk for a severe infectious event (SIE), according to findings from a single-center, retrospective cohort study conducted at the University Hospital of Toulouse in France.

Results of the analysis were published in International Immunopharmacology.

The chimeric anti-CD20 monoclonal antibody rituximab is a widely prescribed agent for the treatment of autoimmune disease. Rituximab has been shown to induce a rapid, often complete, prolonged depletion of circulating B cells. Between 5% and 56% of patients treated with the agent, however, report the development of hypogammaglobulinemia (ie, gamma globulin level of ≤6 g/L).

The researchers sought to describe the following:

  • The risk for an SIE in the setting of an autoimmune disease other than rheumatoid arthritis following initiation/continuation of rituximab and after a diagnosis of hypogammaglobulinemia;
  • The SIE that developed; and
  • All possible factors linked to development of the SIE.

Read more about ANCA-associated vasculitis

Study inclusion criteria included and age of18 years or more, having received 1 or more doses of rituximab within the year following diagnosis of hypogammaglobulinemia, and having rituximab prescribed for an autoimmune disease, including AAV, multiple sclerosis (MS), and neuromyelitis optica spectrum disorder (NMOSD).

The main study outcome was the occurrence of an SIE within 2 years of the initial rituximab infusion, prescribed after a hypogammaglobulinemia diagnosis. An SIE was defined as “any infectious event that required hospitalization for more than 24 [hours] and/or resulted in patient death.”

One hundred twenty-one participants were enrolled in the study and divided into 3 groups:

  • AAV group: n=48
  • MS/NMOSD group: n=48
  • Other autoimmune disease group: n=25

Results of the study showed that 21.5% (26 of 121) of the patients experienced 1 or more SIE during follow-up. Among these participants, 38.5% were rituximab-naive at initial rituximab infusion and 61.5% were rituximab-pretreated individuals.

Cumulative 2-year incidence rates were 27.6% (95% CI, 15.7-40.9) in the AAV group, 12.7% (95% CI, 5.1-23.9) in the MS/NMOSD group, and 30.6% (95% CI, 13.1-50.3) in the other autoimmune disease group. The median gamma globulin level at initial rituximab infusion was 5.3 g/L in the SIE cohort and 5.6 g/L in the no-SIE cohort (P =.04).

Per regression analysis, the risk for SIE increased as follows:

  • Charlson Comorbidity Index of 3 or greater: odds ratio (OR), 2.77; 95% CI, 1.01 to 7.57
  • Lung disease: OR, 3.20; 95% CI, 1.27 to 7.99
  • Gamma globulin less than 4 g/L: OR, 3.39; 95% CI, 1.02 to 11.19
  • Concomitant corticosteroid treatment: OR, 4.13; 95% CI, 1.63 to 10.44
  • Prior cyclophosphamide exposure: OR, 2.69; 95% CI, 1.10 to 6.61
  • Lymphocyte count of less than 1000 cells/μL: OR, 2.86; 95% CI, 1.12 to 7.21
  • Absence of pneumococcal vaccination: OR, 3.50; 95% CI, 1.41 to 8.70

“These findings may help to inform clinical decision when considering a treatment with rituximab in immunosuppressed patients with autoimmune disease,” the researchers noted. “These results must be confirmed in a multicentric prospective independent cohort of expertise center and randomized trials,” they concluded.


Boumaza X, Lafaurie M, Treiner E, et al. Infectious risk when prescribing rituximab in patients with hypogammaglobulinemia acquired in the setting of autoimmune diseases. Int Immunopharmacol. Published online June 3, 2023. doi:10.1016/j.intimp.2023.110342