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B‐cell repopulation dynamics and drug pharmacokinetics impact SARS‐CoV ‐2 vaccine efficacy in anti‐CD20 ‐treated multiple sclerosis patients
Author(s) -
Asplund Högelin Klara,
Ruffin Nicolas,
Pin Elisa,
Hober Sophia,
Nilsson Peter,
Starvaggi Cucuzza Chiara,
Khademi Mohsen,
Olsson Tomas,
Piehl Fredrik,
Al Nimer Faiez
Publication year - 2022
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.15492
Subject(s) - medicine , seroconversion , rituximab , immunology , cd20 , antibody , confidence interval , memory b cell , cohort , vaccination , b cell
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.