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Hypogammaglobulinemia and severe infections in Multiple Sclerosis patients on anti-CD20 agents: A multicentre study
K Smolik1, F Camilli2, I Panzera2
1Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.
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.
Insights
Hypogammaglobulinemia (HG) is common in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder patients treated with anti-CD20 agents. IgG HG increases severe infection risk, highlighting the need for immunoglobulin monitoring.
Area of Science:
- Immunology
- Neurology
- Pharmacology
Background:
- Hypogammaglobulinemia (HG) is a recognized adverse effect of anti-CD20 monoclonal antibody therapy.
- HG is associated with an increased risk of infections in patients undergoing such treatments.
Purpose of the Study:
- To determine the frequency of HG in Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) patients treated with Ocrelizumab or Rituximab.
- To investigate the association between HG and severe infections (SI).
- To identify predictors for both HG and SI.
Main Methods:
- Retrospective, multicenter study involving 556 patients (190 male, 366 female) with a mean age of 47 years.
- Average follow-up duration was 28 months (range: 12-90 months).
Main Results:
- IgG HG was observed in 20% of patients, and IgM HG in 34%.
- Older age (≥50 years) and increased number of treatment cycles predicted IgG HG.
- Severe infections occurred at a rate of 1.8 per 100 person-years, with non-relapsing-remitting disease phenotypes and IgG HG being significant risk factors.
Conclusions:
- A substantial proportion of patients develop IgG and IgM HG during anti-CD20 therapy.
- IgG HG is linked to a higher risk of severe infections, although overall SI rates were low.
- Monitoring immunoglobulin levels is crucial for personalizing anti-CD20 treatment strategies and managing infection risk.
