Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients

Abstract

ObjectivesVaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients.MethodsWe obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine.ResultsMS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients.ConclusionHumoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

“…Nevertheless, considering that none of the TERI-treated pwMS in any of the studies 16,18,22,25-28 remained seronegative after mRNA vaccination, the suggested blunt caused by TERI may not be generalizable to the mRNA-vaccinated pwMS. Furthermore, lower antibody concentrations compared to UX people were observed in pwMS on TERI homogenously in all studies regardless of the used vaccine, but reached statistical significance only in one 28 . TERI’s mechanism of action – which involves inhibition of rapidly-dividing cells, including activated B-cells – may explain this observation.…”

“…As interpreted, this has been translated into observation of proper humoral despite blunted cellular immunization following COVID-19 vaccination among pwMS on CLAD. Furthermore, the time since the last CLAD dose theoretically affects humoral responses; This was suggested especially by Achiron et al study 26 but did not reach statistical significance, and was not confirmed by other studies 25,28,41 ; It seems the implemented guidelines 1-4 have suggested an adequate amount of post-CLAD vaccination delay to prevent blunted humoral responses, and therefore, made the probable effect unmeasurable. Additionally, although CLAD depletes the memory B-cells 42 , a preliminary study suggested its subsequent doses will not alter pre-existing humoral memory 43 ; Still, there is limited evidence that the longevity of COVID-19 vaccine-induced humoral responses is lower in pwMS on CLAD 26 .…”

“…Compared to UX people, low-certainty evidence did not confirm lower odds of anti-S1 seroconversion among pwMS on NTZ following vaccination (OR [95%CI]: 0.53 [0.24, 1.18]) (Supplementary Figure 7). All pwMS on NTZ in seven studies – including the only two studies using anti-S assays with extractable data 23,36 – seroconverted following vaccination 16,17,23,25,26,28,36 . Although relative effect was measurable in only two of them which contained seronegative UX people 26,28 .…”

“…All pwMS on NTZ in seven studies – including the only two studies using anti-S assays with extractable data 23,36 – seroconverted following vaccination 16,17,23,25,26,28,36 . Although relative effect was measurable in only two of them which contained seronegative UX people 26,28 . Unlike all the other studies, pwMS on NTZ in one study 28 showed significantly lower post-vaccination antibodies compared to UX people.…”

The Effect of Smoking on Humoral Response to COVID-19 Vaccines: A Systematic Review of Epidemiological Studies

“…Another report did not specify the enrolled population. In 17 out of 23 studies, current smokers showed significant lower antibody titre, and in a few reports, highlighted a more rapid lowering of the vaccine-elicited IgG compared with nonsmokers [19,20,[26][27][28][29][30]32,34,[36][37][38][39][40][41]43,44]. In particular, accelerated antibody decline was reported in the prospective assessments by Ferrara et al [20], Zhang et al [27], and Malavazos et al [30].…”