Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

Anat Achiron; Mathilda Mandel; Sapir Dreyer-Alster; Gil Harari; David Magalashvili; Polina Sonis; Mark Dolev; Shay Menascu; Shlomo Flechter; Rina Falb; Michael Gurevich

doi:10.1177/17562864211012835

Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

Ther Adv Neurol Disord. 2021 Apr 22:14:17562864211012835. doi: 10.1177/17562864211012835. eCollection 2021.

Authors

Affiliations

¹ Multiple Sclerosis Center, Sheba Medical Center and The Laura Schwarz-Kipp Research of Autoimmune Diseases, Sackler School of Medicine, Tel-Aviv University, Israel, 2 Derech Sheba, Ramat-Gann, 52621, Israel.
² Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, Israel.
³ School of Public Health, University of Haifa, Israel.
⁴ Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gann, and Sackler School of Medicine, Tel-Aviv University, Israel.

Abstract

Background and aims: The National Multiple Sclerosis Society and other expert organizations recommended that all patients with multiple sclerosis (MS) should be vaccinated against COVID-19. However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. We aimed to characterize humoral immunity in mRNA-COVID-19 MS vaccinees treated with high-efficacy DMTs.

Methods: We measured SARS-CoV-2 IgG response using anti-spike protein-based serology (EUROIMMUN) in 125 MS patients vaccinated with BNT162b2-COVID-19 vaccine 1 month after the second dose. Patients were either untreated or under treatment with fingolimod, cladribine, or ocrelizumab. A group of healthy subjects similarly vaccinated served as control. The percent of subjects that developed protective antibodies, the titer, and the time from the last dosing were evaluated.

Results: Protective humoral immunity of 97.9%, 100%, 100%, 22.7%, and 3.8%, was observed in COVID-19 vaccinated healthy subjects (N = 47), untreated MS patients (N = 32), and MS patients treated with cladribine (N = 23), ocrelizumab (N = 44), and fingolimod (N = 26), respectively. SARS-CoV-2 IgG antibody titer was high in healthy subjects, untreated MS patients, and MS patients under cladribine treatment, within 29.5-55 days after the second vaccine dose. Only 22.7% of patients treated with ocrelizumab developed humoral IgG response irrespective to normal absolute lymphocyte count. Most fingolimod-treated MS patients had very low lymphocyte count and failed to develop SARS-COV-2 antibodies. Age, disease duration, and time from the last dosing did not affect humoral response to COVID-19 vaccination.

Conclusions: Cladribine treatment does not impair humoral response to COVID-19 vaccination. We recommend postponing ocrelizumab treatment in MS patients willing to be vaccinated as a protective humoral response can be expected only in some. We do not recommend vaccinating MS patients treated with fingolimod as a protective humoral response is not expected.

Keywords: COVID-19; SARS-COV-2 IgG; humoral immune response; mRNA vaccine; multiple sclerosis.