Effect of cladribine on COVID-19 serology responses following two doses of the BNT162b2 mRNA vaccine in patients with multiple sclerosis

Abstract

Background multiple sclerosis (MS) patients are treated with immunomodulatory treatments that can influence their ability to develop a protective antibody response to the SARS-CoV-2 vaccine. Vaccine efficacy is important for treatment decision and for patients’ reassurance. The main objective is to assess antibody response to SARS-CoV-2 vaccine in MS patients treated with cladribine. Methods Serology response was tested in 97 participants, 67 MS patients and 30 healthy controls (HCs), using two independent methods, 2–3 weeks following the second dose of the BNT162b2 vaccine. Results HCs (n=30) and MS patients treated with cladribine (n=32) had 100% positive serology response against the SARS-CoV-2 spike protein following the second vaccine dose (mean S1/S2-IgG and RBD-IgG:284.5±104.9, 13041±9411 AU/mL and 226.3±121.4, 10554±11405 AU/mL respectively). Comparable findings were observed for untreated MS patients, and interferon beta-1a-treated MS patients (mean S1/S2-IgG: 282.1±100.1, 276.9±94.31 AU/mL respectively). No correlation was found between lymphocyte counts, treatment duration, or time between cladribine dose and vaccination, and serology response or antibody titers. Conclusion and relevance Cladribine treated MS patients are able to produce antibodies to the SARS-CoV-2 mRNA vaccine. In the era of the COVID-19 pandemic, it is reassuring and important for both patients and physicians and will allow to develop consensus guidelines.

Longitudinal humoral response in MS patients treated with cladribine tablets after receiving the second and third doses of SARS-CoV-2 mRNA vaccine

“…In order to find the long-term vaccine specific serology response in MS patients treated with cladribine tablets we analyzed blood samples 6 and 9-12 months following the second vaccine dose. This study follows our recent report on serology responses 2-3 weeks following second vaccine in patients treated with cladribine tablets ( Brill et al, 2021 ). Thirty-five out of 36 MS patients treated with cladribine tablets and 100% (46/46) of HCs had a positive serology response 6 months after the second vaccine dose.…”

“…To date, several reports show that the majority of MS patients treated with cladribine tablets have positive serology response after receiving two doses of the mRNA vaccine. Nevertheless, it is still unclear whether IgG levels are comparable to HCs ( Capone et al, 2021 , Brill et al, 2021 , Tortorella et al, 2022 , Grothe et al, 2021 , Maniscalco et al, 2022 ).…”

“…Cladribine tablets (Mavenclad), a purine analogue selectively target lymphocytes and causes marked reduction of B cells and a modest reduction in T and NK cells ( Beutler, 1992 , Baker et al, 2017 , Stuve et al, 2019 ). We and others have shown that MS patients treated with cladribine tablets develop a humoral response to two doses of the mRNA SARS-CoV-2 vaccines ( Capone et al, 2021 , Brill et al, 2021 , Tortorella et al, 2022 ). However, only a few studies have examined the effect of cladribine tablets on a long-term humoral response after the second vaccination and data on the response following the third booster vaccine dose is limited ( Achiron et al, 2021 ).…”

Immune responses to SARS‐CoV‐2 vaccination in multiple sclerosis: a systematic review/meta‐analysis

“…1 ). 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 …”

Vaccination and immunotherapies in neuroimmunological diseases

“…Cladribine is a synthetic analogue of deoxyadenosine that is incorporated into DNA, leading to apoptosis and depletion of B cells and T cells, including non-proliferating cells 40 , 41 . No dedicated studies, other than in the context of SARS-CoV-2 vaccination, have been conducted to examine vaccination responses during oral cladribine treatment 42 , 43 . Whether oral cladribine affects immunological memory acquired from previous vaccinations has also not been assessed but patients who are treated with cladribine seem to be capable of mounting an intact cellular response to SARS-CoV-2 mRNA vaccines 44 , 45 .…”