Humoral response and safety of the third booster dose of BNT162b2 mRNA COVID-19 vaccine in patients with multiple sclerosis treated with ocrelizumab or fingolimod

Abstract

Background The assessment of the safety and the humoral response to a third booster dose of the BNT162b2 mRNA COVID-19 vaccine is relevant in patients with Multiple Sclerosis (pwMS) treated with Ocrelizumab (OCR) or Fingolimod (FNG). Methods Serum samples were collected from Healthy controls (HCs) and pwMS treated with OCR or FNG at the following time-points: before the first of two vaccine doses (T0); 8 (T1), 16 (T2), 24 (T3) weeks after the first dose; within 8 weeks before (T0b) and after (T1b) the booster dose. IgG antibodies to SARS-CoV-2 trimeric spike protein (Anti-TSP IgG) were quantified and expressed as binding antibody units (BAU)/mL. Results 40 HCs, 28 pwMS on OCR and 19 on FNG were included. At T0b 12 (42.9%) pwMS on OCR and 6 (31.6%) on FNG were still positive while, at T1b 16 (57.14%) pwMS on OCR and 16 (84.2%) on FNG, passed the threshold of positivity. The increase of Anti-TSP IgG levels at T1b was higher for: (i) HCs with respect to OCR (p < 0.001) and FNG (p = 0.032) groups; (ii) pwMS on FNG compared with pwMS on OCR (p < 0.001). No socio-demographic, clinical or laboratory variables were able to predict the anti-TSP IgG increase between T0b and T1b. Neither clinical relapses nor severe adverse events were reported in pwMS after each dose of vaccine. Conclusions The third booster dose of BNT162b2 mRNA vaccine to OCR- and FNG-treated pwMS revives the humoral response, independently of any clinical variable, and manifests a good safety and tolerability profile.

Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study

“…Regarding the effects of the first booster dose of vaccine, at T3 we observed a strong upregulation of the humoral response in both treated and untreated patients, although the humoral responses observed in patients treated with anti-CD20 (OCR) and FTY remained significantly lower than those observed in untreated patients ( Table 3 and 4 ). Yet, the first booster dose significantly increased anti-S levels even in most patients taking these immunosuppressive therapies, in line with other studies ( 14 ). For example, in anti-N negative patients under OCR and FTY, median anti-S antibody levels were, respectively, 40.5 and 28.6-fold higher at T3 than at T1.…”

The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

“…Therefore, ways to improve/optimize vaccination responses will be beneficial ( Sullivan et al, 2022 *). Although, repeated boosting can increase the titres of SARS-CoV-2 specific-antibodies in some people ( Tallantyre et al, 2022a , Milo et al, 2022 , Capuano et al, 2022 , Achtnichts et al, 2022 ), uninterrupted S1PR modulator treatment is currently often associated with a blunted vaccination response ( Pitzalis et al, 2021 , Tallantyre et al, 2022a , Louapre et al, 2022 *), ( Meyer-Arndt et al, 2022 , Akgün et al, 2022 *), ( Scn et al, 2022 ). A long-period of fingolimod discontinuation, to allow recovery of lymphocytes, may increase the chance of a vaccine-induced antibody response, but risks disease breakthrough that can occur within a few weeks of discontinuation ( Barry et al, 2019 , Achtnichts et al, 2022 ).…”

Serology results after COVID vaccine in multiple sclerosis patients treated with fingolimod

“…We also showed a strong relationship between antibody development and age and duration of treatment, as well as between antibody titer and age and duration of treatment. Therefore, we cannot afford not to recommend vaccination in MS patients treated with fingolimod, especially as research has shown that the third booster dose (mRNA vaccine in the study) revives the humoral response independently of any clinical variables [49] . Further studies on this topic are needed to support our results, especially regarding the influence of the duration of treatment on antibody development and titer (scarce data at present), although one study supports our point and also shows a relationship between treatment duration and vaccine response [50] , ideally with a larger sample size and a measurement of cellular immunity.…”