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

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.