[Immunological foundations of neurological diseases]. / Immunologische Grundlagen neurologischer Erkrankungen.

BACKGROUND: Neurodegenerative diseases represent an increasing challenge in ageing societies, as only limited treatment options are currently available. OBJECTIVE: New research methods and interdisciplinary interaction of different disciplines have changed the way neurological disorders are viewed and paved the way for the comparatively new field of neuroimmunology, which was established in the early 1980s. Starting from neurological autoimmune diseases, such as multiple sclerosis, knowledge about the involvement of immunological processes in other contexts, such as stroke or traumatic brain injury, has been significantly expanded in recent years. MATERIAL AND METHODS: This review article provides an overview of the role of the immune system and the resulting potential for novel treatment approaches. RESULTS: The immune system plays a central role in fighting infections but is also able to react to the body's own signals under sterile conditions and cause inflammation and subsequent adaptive immune responses through the release of immune mediators and the recruitment and differentiation of certain immune cell types. This can be beneficial in initiating healing processes; however, chronic inflammatory conditions usually have destructive consequences for the tissue and the organism and must be interrupted. CONCLUSION: It is now known that different cells of the immune system play an important role in neurological diseases. Regulatory mechanisms, which are mediated by regulatory T cells or Th2 cells, are usually associated with a good prognosis, whereas inflammatory processes and polarization towards Th1 or Th17 have a destructive character. Novel immunomodulators, which are also increasingly being used in cancer treatment, can now be used in a tissue-specific manner and therefore offer great potential for use in neurological diseases.

[Ofatumumab in the treatment of multiple sclerosis - A summary of preclinical and clinical data]. / Ofatumumab in der Behandlung der Multiplen Sklerose ­ Eine Übersicht der präklinischen und klinischen Daten.

BACKGROUND: B-cell targeted therapies are highly effective in multiple sclerosis (MS). Most of these therapies are administered intravenously at long intervals. Ofatumumab, an anti-CD20 antibody that is administered subcutaneously at low doses on a monthly basis due to its high affinity to the target structure, became available for the treatment of MS in 2021. METHODS: An overview of practice-relevant immunological and clinical data on ofatumumab is provided. RESULTS: The high affinity of ofatumumab to the target structure allows low dose and low volume administration, with the release and absorption profile after subcutaneous application allowing for high concentrations in the lymph nodes and gradual depletion of B-cells. Rapid onset of action is achieved as well as B-cell repletion within a few months in case of discontinuation of therapy. Long-term data show stable IgG levels over up to four years and high efficacy with respect to relapse rate, progression, and cognition. According to current study data, the effect compared to teriflunomide is greater the earlier therapy is initiated. Ofatumumab has a specific B-cell depletion pattern. CD20 expressing B-cell progenitor cells in the bone marrow are preserved and therefore also the inducibility and differentiation of plasma cells. The formation of a humoral immunological memory is therefore possible. Four-year study data showed no abnormalities in the rate of severe infections or malignancies. CONCLUSIONS: Ofatumumab is an innovative B-cell targeted therapy. It is highly effective with a good safety and tolerability profile, well controllable and maintains immunocompetence against pathogens.

Neutralizing antibody titers over 12 months after SARS-CoV-2 mRNA vaccine booster in patients with relapsing multiple sclerosis continuously treated with ofatumumab.

Booster vaccinations against SARS-CoV-2 are recommended 6-12 months after the last dose or infection in elderly and high-risk groups. The present analysis aims to evaluate whether an interval shorter than 12 months is required in multiple sclerosis patients receiving ofatumumab. Neutralizing antibody status over 1 year in patients receiving booster vaccination in the non-interventional, multicenter KYRIOS study under continued ofatumumab treatment was analyzed. Fifteen patients were included. At the time of the first booster vaccination, ten patients were seropositive for neutralizing antibodies, four patients were seronegative, and for one patient, no baseline levels were available. All patients who were seropositive at baseline showed >2-fold increase in neutralizing antibody titers after the first booster and two patients (20%) showed a >10-fold increase. Among seronegative patients, three (75%) had a >10-fold increase in neutralizing antibody titers. Seropositivity was maintained in almost all patients until month 12. One initially seronegative patient had less than 2-fold increase in neutralizing antibody titers after the booster vaccination and can be considered a non-responder. Most patients with continued ofatumumab treatment are able to maintain permanent seropositivity and therefore presumably constant protection against severe courses of COVID-19 if repeated booster vaccinations are applied.