Humoral and cellular immunity in convalescent COVID-19 people with multiple sclerosis treated with ofatumumab

Adamec, Ivan; Rogić, Dunja; Penz, Monika-Gabriele; Braun, C; Habek, Mario

doi:10.1016/j.jneuroim.2021.577788

Cited by 12 publications

(7 citation statements)

References 24 publications

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“…One patient had ofatumumab dosing temporarily interrupted because of low IgM. None of the three patients without circulating B cells developed detectable antibodies to SARS-CoV-2 [ 40 ]. Conversely, all three patients tested for SARS-CoV-2 had T-cell responses detected by interferon-γ ELISpot assay.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

et al. 2022

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Introduction The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. Methods COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. Results As of 25 September 2021, 245 of 1703 patients (14.3%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients were hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19–affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious ( n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. Conclusion COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-022-00341-z.

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Section: Discussionmentioning

confidence: 99%

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

et al. 2022

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“…The report of a patient followed in the ASCLEPIOS-extension study who was 42 months under ofatumumab showed effective IgM and IgG response against the spike protein following COVID-19 infection despite complete B cell depletion ( 13 ). Another case series of four patients documented strong T cell response in patients without titer against the spike protein following COVID-19 infection ( 14 ). Data derived from the phase 3 study ALITHIOS which investigated ofatumumab vs. teriflunomide in MS documented that 245 of 1703 patients (14.3%) reported a COVID-19 disease of whom 44.1% had a mild and 46.5% a moderate course ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

Faissner

Heitmann²,

Plaza-Sirvent³

et al. 2022

Front. Immunol.

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ObjectiveThe pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood.MethodsWe here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls.ResultsWe show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1).InterpretationIn summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.

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“…However, this patient had a 28-week break in the intake of OFA caused by lower IgM levels. The level of CD19 before infection was 6.4% [ 9 ].…”

Section: Discussion/conclusionmentioning

confidence: 99%

Immunocompetence after SARS-CoV-2 Infection in a Patient with Multiple Sclerosis Treated with Ofatumumab: A Case Report

Jasińska

2022

Case Rep Neurol

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Ofatumumab is the first fully human anti-CD20 monoclonal antibody that, on March 26, 2021, was approved by the EMA to treat patients with relapsing multiple sclerosis. This paper aimed to present a case confirming the ability to produce and maintain anti-SARS-CoV-2 antibodies in a patient treated with ofatumumab for over 4 years. The course of the infection was moderate, and the patient did not require hospitalization. Antibody measurements were performed five times post-COVID-19 infection. The first test was performed in the fourth month (131 days), and the last, over 1 year after the infection. To date, only 2 cases have been published describing the ability of a patient treated with the same drug to produce antibodies against SARS-CoV-2, although the observation was conducted over a shorter period. In our case study, we have 15-month follow-up data. The patient was not vaccinated and additionally received suppressive steroid therapy due to the relapse. We observed an increase in antibodies up to 10 months from the infection. The case under analysis suggests that patients treated with ofatumumab, despite complete peripheral B-cell depletion, can produce and maintain a long-lasting immune response.

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Humoral and cellular immunity in convalescent COVID-19 people with multiple sclerosis treated with ofatumumab

Cited by 12 publications

References 24 publications

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

Immunocompetence after SARS-CoV-2 Infection in a Patient with Multiple Sclerosis Treated with Ofatumumab: A Case Report

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