Hospitalisations and humoral COVID-19 vaccine response in vaccinated rituximab-treated multiple sclerosis patients.

Publisher: Elsevier B. V Country of Publication: Netherlands NLM ID: 101580247 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-0356 (Electronic) Linking ISSN: 22110348 NLM ISO Abbreviation: Mult Scler Relat Disord Subsets: MEDLINE

Original Publication: [Amsterdam] : Elsevier B. V.

Rituximab*/administration & dosage ; Rituximab*/therapeutic use ; Rituximab*/pharmacology ; Multiple Sclerosis*/immunology ; Multiple Sclerosis*/drug therapy ; Multiple Sclerosis*/blood ; COVID-19*/immunology ; COVID-19*/prevention & control ; COVID-19 Vaccines*/immunology ; COVID-19 Vaccines*/administration & dosage ; Immunologic Factors*/administration & dosage ; Immunologic Factors*/pharmacology ; Hospitalization*/statistics & numerical data; Humans ; Female ; Male ; Adult ; Middle Aged ; SARS-CoV-2/immunology ; Antibodies, Viral/blood ; Registries ; Immunity, Humoral/drug effects ; Immunity, Humoral/immunology ; Norway/epidemiology

Background: Patients with multiple sclerosis (MS) treated with anti-CD20 therapies such as rituximab may have increased risk of severe COVID-19 disease. Vaccination induces protective immunity, but humoral vaccine response is known to be attenuated in rituximab-treated MS-patients-patients, which has indicated a need for real world data on severe morbidity and mortality from COVID-19 after vaccination.
Methods: Rituximab-treated patients treated at Haukeland University Hospital were identified through the National MS Registry and invited to participate in the study by giving a consent and providing a blood sample 3 weeks or later after ordinary COVID-19- vaccination, i.e. 2 doses given with a standard interval of 3 weeks. Blood samples were analysed with Enzyme-Linked Immunosorbent assay (ELISA) to evaluate humoral vaccine response with screening test against receptor-binding domain (RBD) and confirmatory Spike IgG-specific ELISA. A haemagglutination test (HAT) was performed as a marker of neutralizing antibodies. Patient serum concentration of rituximab were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). Registry data from the Norwegian MS registry and information on hospitalization from patient records were collected and linked to laboratory results.
Results: 111 patients were included in the study. A total of 7 (6.3%) were hospitalized due to COVID-19 disease during the observation period. No patient was admitted to ICU and there were no deaths. 34.2% did not have detectable titre of SARS CoV-2 Spike IgG antibodies, 72.1% did not have a detectable titre of SARS CoV-2 RBD antibodies, and 88.2% did not have a detectable HAT titre. There was a correlation between hospitalisation and the absence of SARS CoV-2 Spike IgG antibody titre, and between hospitalisation and MS disease duration, as well as between spike IgG antibody titre and CD19 B-cell count, time since last rituximab infusion, cumulative rituximab treatment time and total IgG level in the patients.
Conclusion: A substantial proportion of rituximab-treated MS-patients-patients did not have detectable humoral vaccine responses after 2 doses of COVID-19 vaccination. Despite this, the cumulative percentage of patients hospitalized with COVID-19 disease throughout the observation period of 22 months was low, and no patients required ICU treatment. The results support that vaccinated MS-patients treated with rituximab have a protective effect against serious Covid-19 infection.
Competing Interests: Declaration of competing interest Hilde Torgauten, Therese Bredholt Onyango, Sonja Ljostveit, Erik I. Hallin, Trond T. Serkland, Silje Skrede, Nina Langeland and Rebecca Jane Cox have no declarations relevant to the field of multiple sclerosis. Stig Wergeland has received honoraria for lecturing and advice from Biogen, Janssen and Sanofi. Kjell-Morten Myhr has received unrestricted research grants to his institution and scientific advisory board, and speaker honoraria from Almirall, Biogen, Genzyme, Merck, Novartis, Roche and Teva; and has participated in clinical trials organized by Biogen, Merck, Novartis, and Roche. Øivind Torkildsen has received speaker honoraria from or and served on scientific advisory boards for Biogen, Sanofi-Aventis, Merck, Teva, Gilead and Novartis; and has participated in clinical trials organized by Biogen, Merck, Novartis, and Roche.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Keywords: Anti CD20 monoclonal antibody; COVID-19; Multiple sclerosis; Vaccine response; rituximab

4F4X42SYQ6 (Rituximab)
0 (COVID-19 Vaccines)
0 (Immunologic Factors)
0 (Antibodies, Viral)

Date Created: 20240719 Date Completed: 20240820 Latest Revision: 20240820

20240821

10.1016/j.msard.2024.105770

39029342