Safety and efficacy of a third booster dose of BNT162b2 mRNA Covid-19 vaccine in patients with multiple sclerosis treated with ocrelizumab or fingolimod

ABSTRACT

Introduction: Patients with Multiple Sclerosis (pwMS) treated with Ocrelizumab (OCR) and Fingolimod (FNG) have shown a blunted humoral response to the first two doses of the BNT162b2 mRNA Covid-19 vaccine. The assessment of the safety and the humoral response to a third booster dose of the same vaccine is therefore relevant within this population. Aim(s) To investigate the safety and the humoral response to a third booster dose of the BNT162b2 mRNA Covid-19 vaccine in pwMS on OCR/FNG, comparing it with age- and sex-matched healthy controls (HCs). Method(s) Serum samples were collected from HCs and pwMS treated with OCR or FNG at the following scheduled 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. Result(s) 40 HCs and 47 pwMS (28 on OCR and 19 on FNG) were included in the study. All (100%) HCs mounted a positive (>33.8 BAU/mL) humoral response at T1 and preserved it until (T2-T3- T0b) and after (T1b) the third booster dose. At T0b only 12 (42.9%) pwMS on OCR and 6 (31.6%) on FNG were positive while, at T1b 16 (57.14%) pwMS on OCR and 16 (84.2%) on FNG, passed the threshold of positivity. Anti-TSP IgG titers in HCs were significantly higher than those of pwMS on OCR and on FNG at all time points, while no differences were found at all time points between pwMS on OCR and those on FNG. HCs showed a significant higher (relative) increase of Anti-TSP IgG levels at T1b with respect to OCR (p<.001) and FNG (p=.032) groups. The increase of Anti-TSP IgG levels in the pwMS on FNG was significantly higher than those in the OCR group (p<.001). No socio-demographic, clinical, or laboratory variables were able to predict the increase of anti-TSP IgG levels between T0b and T1b. Neither clinical relapses nor severe adverse events were reported in pwMS after each of the three doses of vaccine during the follow- up period. Conclusion(s) The administration of a third booster dose of BNT162b2 mRNA Covid-19 vaccine to OCR- and FNG-treated pwMS is able to revive the humoral response, independently of any demographic, clinical or laboratory variable, and confirms a good safety and tolerability profile, not only in terms of adverse events but also in terms of MS relapses.