Hypogammaglobulinemia and severe infections in Multiple Sclerosis patients on anti-CD20 agents: A multicentre study

Abstract

Background

Hypogammaglobulinemia (HG) is a known side effect of treatment with anti-CD20 monoclonal antibodies, and it is associated with the risk of infections.

Objectives

Aim of this retrospective multicentre study was to assess the frequency of HG in Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder patients treated with Ocrelizumab or Rituximab and its association with the occurrence of severe infections (SI). Furthermore, predictors of HG and SI were sought.

Methods

We included 556 patients (190M, 366F, mean age: 47 years) with a mean follow-up of 28 months (range 12-90 months).

Results

IgG HG occurred in 20% and IgM HG in 34% of patients. At multivariable analysis, the risk of IgG HG was influenced by an older age (≥50 years) (OR 1.64, 95%CI: 1.06-2.54, p=0.027), and by the number of treatment cycles (OR: 1.20, 95%CI: 1.09-1.33, p<0.001).

A total of 25 SI occurred (100 person-years rate: 1.8), with a disease phenotype other than relapsing-remitting (OR 1.50, 95%CI: 1.02-2.20; p=0.039) and IgG HG (OR 2.65, 95%CI: 1.15-6.12; p=0.022) increasing its risk.

Conclusions

IgG and IgM HG occurred in a considerable proportion of patients. IgG HG increased the risk of SI, which were, nevertheless, relatively infrequent. Our results highlight the importance of monitoring immunoglobulin levels during treatment with anti-CD20 agents, to personalize treatment strategies.