An overview of pivotal trials and real-world evidence for CD20-depleting therapy in multiple sclerosis : Immunotherapy with rituximab, ocrelizumab, and ofatumumab.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system leading to demyelination and neurodegeneration of brain tissue. For a long time, research focused on T cells as the primary mechanism of disease. Driven by reports on the clinical results of B cell-depleting therapies, this therapeutic approach has come into focus in the last decade, and new highly effective treatments have been developed and are now complementing the therapeutic landscape. This review provides an overview of the development of B cell-depleting therapies and shows the advantages and disadvantages of current developments. In addition, we discuss basic considerations for CD20-depleted MS patients in the face of the COVID-19 pandemic.

SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis Treated with Fingolimod: Protective Humoral Immune Responses May Develop after the Preferred Third Shot.

Evidence suggests limited development of protective IgG responses to mRNA-based vaccines in sphingosine-1-phosphate receptor (S1PR)-modulator treated individuals with multiple sclerosis (MS). We studied the extent of the humoral immune response after the preferred third mRNA SARS-CoV-2 vaccine in S1PR-modulator treated people with MS (pwMS) and insufficient IgG responses after the standard immunization scheme. Eight pwMS that were treated with fingolimod received a third homologous SARS-CoV-2 mRNA vaccine dose, either the Moderna's mRNA-1273 or Pfizer-BioNTech's BNT162b2 vaccine. We quantified the serum levels of IgG antibodies against the receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered protective. After the third vaccination, we found clinically relevant IgG titers in four out of eight individuals (50%). We conclude that the humoral immune response may reach protective levels after the third preferred dose of the homologous SARS-CoV-2 mRNA vaccine. Vaccine shots in S1PR-modulator treated pwMS ahead of schedule may be a strategy to overcome insufficient humoral immune responses following the standard vaccination scheme.