B-cell repopulation dynamics and drug pharmacokinetics impact SARS-CoV-2 vaccine efficacy in anti-CD20-treated multiple sclerosis patients

Eur J Neurol. 2022 Nov;29(11):3317-3328. doi: 10.1111/ene.15492. Epub 2022 Jul 20.

Abstract

Background and purpose: Recent findings document a blunted humoral response to SARS-CoV-2 vaccination in patients on anti-CD20 treatment. Although most patients develop a cellular response, it is still important to identify predictors of seroconversion to optimize vaccine responses.

Methods: We determined antibody responses after SARS-CoV-2 vaccination in a real-world cohort of multiple sclerosis patients (n = 94) treated with anti-CD20, mainly rituximab, with variable treatment duration (median = 2.9, range = 0.4-9.6 years) and time from last anti-CD20 infusion to vaccination (median = 190, range = 60-1032 days).

Results: We find that presence of B cells and/or rituximab in blood predict seroconversion better than time since last infusion. Using multiple logistic regression, presence of >0.5% B cells increased probability of seroconversion with an odds ratio (OR) of 5.0 (95% confidence interval [CI] = 1.0-28.1, p = 0.055), whereas the corresponding OR for ≥6 months since last infusion was 1.45 (95% CI = 0.20-10.15, p = 0.705). In contrast, detectable rituximab levels were negatively associated with seroconversion (OR = 0.05, 95% CI = 0.002-0.392, p = 0.012). Furthermore, naïve and memory IgG+ B cells correlated with antibody levels. Although retreatment with rituximab at 4 weeks or more after booster depleted spike-specific B cells, it did not noticeably affect the rate of decline in antibody titers. Interferon-γ and/or interleukin-13 T-cell responses to the spike S1 domain were observed in most patients, but with no correlation to spike antibody levels.

Conclusions: These findings are relevant for providing individualized guidance to patients and planning of vaccination schemes, in turn optimizing benefit-risk with anti-CD20.

Keywords: B-cell depletion; SARS-CoV-2; multiple sclerosis; rituximab; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • B-Lymphocytes* / cytology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19* / prevention & control
  • Humans
  • Immunoglobulin G
  • Interferon-gamma
  • Interleukin-13
  • Multiple Sclerosis* / drug therapy
  • Rituximab / pharmacokinetics
  • Rituximab / therapeutic use
  • SARS-CoV-2
  • Vaccination
  • Vaccine Efficacy

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin G
  • Interleukin-13
  • Rituximab
  • Interferon-gamma