Vaccination characteristics.

Vaccination characteristics.

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Background: Few data exist on how ofatumumab treatment impacts SARS-CoV-2 booster vaccination response. Methods: KYRIOS is an ongoing prospective open-label multicenter study on the response to initial and booster SARS-CoV-2 mRNA vaccination before or during ofatumumab treatment in relapsing MS patients. The results on the initial vaccination co...

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... mRNA vaccines by BioNTech/Pfizer were administered as the booster, with an average of 26 weeks after the second dose both in booster cohort 1 and booster cohort 2. The mean time between booster vaccination and the start of ofatumumab in booster cohort 1 was 0.87 months. In booster cohort 2, ofatumumab was started on average 1.87 months before booster vaccination (Table 2). Cohort 3 included 20 patients from the AMA-VACC study treated with DMF, GA, IFN or TF, of whom 18 patients received a booster vaccination. ...

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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...
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... These results underscore the importance of booster vaccination in ofatumumab-treated patients, as it enhances the immune response regardless of their treatment status during the initial vaccination. 54 While the end of the pandemic has significantly reduced the immediate risk of SARS-CoV-2 in the population, it remains crucial to continue analyzing the rates of severe COVID-19 disease and vaccine responses which can have broader implications for responding to other viral infections and enhancing future vaccination strategies. ...
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Targeting B cells through monoclonal antibodies against CD20 has emerged as a highly effective strategy in managing disease activity in patients with relapsing forms of multiple sclerosis. This efficacy was initially demonstrated with rituximab and further affirmed with ocrelizumab. Ofatumumab is the first fully human IgG1 monoclonal antibody (mAb) approved for the treatment of MS. It is characterized by its convenient self-administered regimen of once-monthly subcutaneous injections. Its human antibody nature contributes to a significantly lower risk of immunogenicity compared to rituximab. Clinical trials have consistently shown its effectiveness in significantly reducing annualized relapse rates, MRI-detected lesion activity, and disability progression when compared to teriflunomide, a standard therapy for MS. Additionally, ofatumumab exhibits a manageable tolerability profile, with adverse events primarily comprising infections and injection-related reactions. This review describes ofatumumab pharmacology, core clinical trial data and clinical efficacy in addition to safety issues.
... Die erhaltene Fähigkeit zur Induktion und Ausdifferenzierung von Plasmazellen und die stabilen IgG-Spiegel dürften auch bei Impfungen eine Rolle spielen. Die Antikörper-Immunantwort auf eine SARS-CoV-2-Boosterimpfung war in der KYRIOS-Studie selbst unter stabiler Ofatumumab-Therapie hoch und unterschied sich nicht wesentlich von einer Boosterimpfung vor Ofatumumab-Therapie. Drei von vier zuvor seronegativen Patienten konnten durch eine Boosterimpfung eine Serokonversion erreichen [28]. Dass die Boosterimpfung auch bei Patienten mit Erstimpfung während Ofatumumab-Behandlung zu einem weiteren Anstieg der neutralisierenden Antikörpertiter führte, deutet auf die Entwicklung eines humoralen immunologischen Gedächtnisses hin. ...
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Zusammenfassung Hintergrund B-Zell-gerichtete Therapien sind hochwirksam bei Multipler Sklerose (MS). Die meisten dieser Therapien sind in langen Intervallen intravenös zu applizieren. Seit 2021 ist aber auch Ofatumumab zur Behandlung der MS zugelassen, ein Anti-CD20-Antikörper, der aufgrund hoher Affinität zur Zielstruktur niedrig dosiert und monatlich subkutan verabreicht wird. Methoden Es wird eine Übersicht über aktuelle praxisrelevante immunologische und klinische Daten zu Ofatumumab gegeben. Ergebnisse Die hohe Affinität von Ofatumumab zur Zielstruktur erlaubt eine niedrige Dosierung in kleinem Volumen, wobei das Freisetzungs- und Resorptionsverhalten nach subkutaner Applikation hohe Konzentrationen in den Lymphknoten und eine graduelle B-Zell-Depletion ermöglicht. Ein schneller Wirkeintritt ist ebenso gegeben wie eine B-Zell-Repletion innerhalb weniger Monate bei Therapieabbruch. Langzeitdaten zeigen über bis zu vier Jahre stabile IgG-Spiegel und eine nachhaltig hohe Wirksamkeit hinsichtlich Schubrate, Progression und Kognition, wobei der Vorteil gegenüber Teriflunomid in den klinischen Studien größer war, je früher die Therapie begonnen wurde. Ofatumumab zeigt ein spezifisches B-Zell-Depletionsmuster. CD20-exprimierende B-Zell-Vorläuferzellen im Knochenmark bleiben erhalten und damit auch die Induzierbarkeit und Ausdifferenzierung von Plasmazellen. Die Ausbildung eines humoralen immunologischen Gedächtnisses ist daher möglich. Vierjahres-Studiendaten zeigten keine Auffälligkeiten in der Rate schwerer Infektionen oder maligner Erkrankungen. Schlussfolgerung Ofatumumab ist eine innovative B-Zell-gerichtete Therapie. Es ist hochwirksam bei guter Sicherheit und Verträglichkeit und gut steuerbar bei erhaltener Immunkompetenz gegenüber Pathogenen.
... Ofatumumab treatment interruption is not necessary for the purpose of SARS-CoV-2 mRNA vaccination. 3,4 However, data are still lacking on the sustainability of the immune response and the necessary frequency of booster vaccinations in MS patients treated with ofatumumab. It is important that booster vaccinations are able to maintain adequate immune response (i.e., seropositivity) under continued ofatumumab therapy, as treatment interruption is associated with an increased risk of relapses and disease progression. ...
... Results on the immune responses 1 month after initial vaccination and 1 month after booster vaccination during continued ofatumumab treatment have already been published. 3,4 New data are now available from the KYRIOS study on the maintenance of the immune response over 12 months after booster vaccination. ...
... Details on the design of the KYRIOS study and patient characteristics have been published previously. 3,4 Here, we report neutralizing antibody status over 1 year in patients who received only their booster vaccination in the KYRIOS study under continued ofatumumab treatment. These patients are a subgroup of cohort 2 and had been initially vaccinated outside of the KYRIOS study either during treatment with other DMT than ofatumumab or without receiving DMT. ...
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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.
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OBJECTIVE: The study aims to show the efficacy/effectiveness and safety of vaccinations in patients with multiple sclerosis. MATERIALS AND METHODS: This systematic review was conducted following the guidelines of the Cochrane Collaboration and the meta-analysis of observational studies in epidemiology (MOOSE). RESULTS: At the end of the review process, 133 studies were included; the bibliographic search was conducted on PubMed/Medline and Scopus, combining free text and words. CONCLUSIONS: In general, vaccinations do not seem to aggravate multiple sclerosis (MS) or increase the probability of relapse, particularly for inactivated vaccines and, in general, for the rest of the vaccines. However, it is advisable, especially for vaccines with a live attenuated virus, to carefully evaluate the risks and benefits of these vaccinations ; as regards the effectiveness in relation to the drug taken, there is great variability in response. In particular, vaccinations are less effective in patients undergoing therapy with anti-CD20 and S1P modulators. At the same time, a small response is likely to be better than none. Whenever possible, vaccinations should be offered and recommended to patients with multiple sclerosis.