scholarly journals Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies

2021 ◽  
Author(s):  
Maria Pia Sormani ◽  
Irene Schiavetti ◽  
Matilde Inglese ◽  
Luca Carmisciano ◽  
Alice Laroni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Cumulative Incidence ◽  
Vaccine Dose ◽  
Ministry Of Health ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Antibody Levels ◽  
The Impact

Background. Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to mRNA-based SARS-CoV-2 vaccines, while the degree of such responses is unimpaired and similar in pwMS treated with other disease modifying therapies (DMTs), or untreated. However, the nature of the SARS-CoV-2 vaccine-induced immune response is based also on cellular immunity and there is emerging evidence that anti-SARS-CoV-2 specific CD4 and CD8 T cell responses can be detected after vaccination also in patients with low antibody levels. In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection and to identify correlates of reduced protection in frail vaccinated pwMS on different DMTs. Methods. We designed a long term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) , a prospective multicenter cohort study enrolling pwMS scheduled for SARS-CoV-2 vaccination with mRNA vaccines and tested for SARS-CoV-2 antibodies before and after the second vaccine dose. These patients were followed with periodic phone calls up to a mean time of 6 months, and all the SARS-CoV-2 breakthrough infections were registered. The impact of DMTs on cumulative incidence of breakthrough Covid-19 cases was presented by Kaplan-Meier curves. A multivariable logistic model was run to assess factors associated to a higher risk of breakthrough infections. Findings. 1705 pwMS (81.6% BNT162b2 and 18.4% mRNA-1273) had a full vaccination cycle (2 vaccine doses, 21/28 days apart). Of them, 1509 (88.5%) had blood assessment 4 weeks after the second vaccine dose. During follow-up, 23 breakthrough Covid-19 infections (cumulative incidence: 1.5%, SE=0.3%) were detected after a mean of 108 days after the second dose (range, 18-230). Of them, 9 were on ocrelizumab, one on rituximab, 4 on fingolimod, 6 on dimethyl-fumarate, one on teriflunomide, and 2 were untreated. Just two cases (a woman on ocrelizumab and a man on teriflunomide) required hospitalization. The probability to be infected was associated only with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.63, p=0.007); an antibody level of 660 U/mL was calculated as the cut-off for higher risk of infection. Interpretation. Our data show that the risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response. Funding. FISM [2021/Special-Multi/001]; the Italian Ministry of Health grant Progetto Z844A 5x1000. Italian Ministry of Health: Ricerca Corrente to IRCCS Ospedale Policlinico San Martino.

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

2021 ◽  
Vol 14 ◽  
pp. 175628642110128
Author(s):  
Anat Achiron ◽  
Mathilda Mandel ◽  
Sapir Dreyer-Alster ◽  
Gil Harari ◽  
David Magalashvili ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Humoral Immunity ◽  
Lymphocyte Count ◽  
Healthy Subjects ◽  
Vaccine Dose ◽  
Humoral Response ◽  
High Efficacy ◽  
Disease Modifying Therapies ◽  
Disease Modifying

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.

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Maristella Pitzalis ◽  
Maria Laura Idda ◽  
Valeria Lodde ◽  
Annalisa Loizedda ◽  
Monia Lobina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Smoking Status ◽  
Humoral Response ◽  
Disease Modifying Therapies ◽  
Significant Difference ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Humoral Responses ◽  
The Impact

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.

scholarly journals Effect of different disease-modifying therapies on humoral response to BNT162b2 vaccine in Sardinian multiple sclerosis patients

2021 ◽  
Author(s):  
Maristella Pitzalis ◽  
Maria Laura Idda ◽  
Valeria Lodde ◽  
Annalisa Loizedda ◽  
Monia Lobina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Smoking Status ◽  
Humoral Response ◽  
Disease Modifying Therapies ◽  
Significant Difference ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Humoral Responses ◽  
The Impact

Objectives: Vaccination 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. Methods: We 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. Results: MS 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. Conclusion: Humoral 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.

scholarly journals Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US

Neurology ◽  
2018 ◽  
Vol 91 (19) ◽  
pp. e1778-e1787 ◽  
Author(s):  
Kristen M. Krysko ◽  
Jennifer Graves ◽  
Mary Rensel ◽  
Bianca Weinstock-Guttman ◽  
Gregory Aaen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effect ◽  
Pediatric Patients ◽  
Dimethyl Fumarate ◽  
Short Term ◽  
Pediatric Multiple Sclerosis ◽  
Disease Modifying Therapies ◽  
The Us ◽  
Disease Modifying

ObjectiveTo characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age.MethodsThis is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric MS Centers. DMT use, including duration, dose, and side effects, was analyzed. Newer DMTs were defined as agents receiving Food and Drug Administration approval or with increased use in adult MS after 2005.ResultsAs of July 2017, 1,019 pediatric patients with MS (n = 748) or CIS (n = 271) were enrolled (65% female, mean onset 13.0 ± 3.9 years, mean follow-up 3.5 ± 3.1 years, median 1.6 visits per year). Of these, 78% (n = 587) with MS and 11% (n = 31) with CIS received DMT before 18 years of age. This consisted of at least one newer DMT in 42%, including dimethyl fumarate (n = 102), natalizumab (n = 101), rituximab (n = 57), fingolimod (n = 37), daclizumab (n = 5), and teriflunomide (n = 3). Among 17%, the initial DMT prescribed was a newer agent (36 dimethyl fumarate, 30 natalizumab, 22 rituximab, 14 fingolimod, 2 teriflunomide). Over the last 10 years, the use of newer agents has increased, particularly in those ≥12 years and to lesser extent in those <12 years. The short-term side effect profiles of newer DMTs did not differ from those reported in adults.ConclusionNewer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management.

scholarly journals Protecting people with multiple sclerosis through vaccination

2020 ◽  
Vol 20 (6) ◽  
pp. 435.1-445
Author(s):  
Saúl Reyes ◽  
Mary Ramsay ◽  
Shamez Ladhani ◽  
Gayatri Amirthalingam ◽  
Neena Singh ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Patient Education ◽  
Current Literature ◽  
Morbidity And Mortality ◽  
Disease Modifying Therapies ◽  
Specific Advice ◽  
Disease Modifying ◽  
Cost Efficient ◽  
To Receive

Vaccination is one of the most effective and cost-efficient methods for protecting people with multiple sclerosis (MS) from infections. However, use of vaccines has often been problematic because of misguided concerns that they may exacerbate the disease and/or that some disease-modifying therapies may influence the immune response to immunisations and/or their safety. People with MS risk higher morbidity and mortality from vaccine-preventable infections. It is, therefore, important to address any patient’s reluctance to accept vaccination and to provide clear guidance for clinicians on which vaccinations to consider proactively. We have reviewed the current literature and provide recommendations regarding vaccines in adults with MS, including specific advice regarding vaccination safety in patients receiving—or going to receive—disease-modifying therapies, vaccination during pregnancy, pretravel counselling and patient education.

scholarly journals Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 88 (6) ◽  
pp. 525-532 ◽  
Author(s):  
Julia Button ◽  
Omar Al-Louzi ◽  
Andrew Lang ◽  
Pavan Bhargava ◽  
Scott D. Newsome ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
First Year ◽  
Time Interval ◽  
Inclusion Criteria ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Retinal Atrophy ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis

Objective:To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT).Methods:A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell + inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression.Results:The effects of glatiramer acetate (GA; n = 48), natalizumab (NAT; n = 46), and interferon-β-1a subcutaneously (IFNSC; n = 35) and intramuscularly (IFNIM; n = 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFNSC- and GA-treated patients exhibited 0.37 μm/y (p < 0.001) and 0.14 μm/y (p = 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFNSC group, GCIP thinning was 1.53 μm/y faster during the first year of therapy vs during the time interval afterwards (p < 0.001).Conclusions:Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials.

Switching first-line disease-modifying therapy after failure: impact on the course of relapsing–remitting multiple sclerosis

2009 ◽  
Vol 15 (1) ◽  
pp. 50-58 ◽  
Author(s):  
A Gajofatto ◽  
P Bacchetti ◽  
B Grimes ◽  
A High ◽  
E Waubant
Keyword(s):  
Multiple Sclerosis ◽  
Initial Therapy ◽  
First Line ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background Options for non-responders to relapsing–remitting multiple sclerosis (RRMS) first-line disease-modifying therapies (DMT) are limited. We explored whether switching first-line DMT is effective. Methods Patients with RRMS who first received interferon-beta (IFNB) or glatiramer acetate (GA) were classified in three categories: DMT change because of suboptimal response, DMT change because of other reasons, and no DMT change during follow-up. Outcomes included annualized relapse rate (ARR) and relapse-free proportions. Results We identified 597 patients who initiated first-line DMT. For patients who did not change DMT ( n = 240), pre-DMT and on-DMT median ARR were 0.50 and 0 ( P < 0.0001). At 24 months, 76% (95%CI = 69–81%) of patients who did not change DMT were relapse-free. Of the 155 who switched because of suboptimal response, 101 switched to another first-line DMT. Median ARR pre-DMT, on first DMT and second DMT were: 0.50, 0.55, and 0.25 for switchers from IFNB to GA (IFNB/GA, n = 12) (pre-DMT versus first DMT: P = 0.92; first versus second DMT: P = 0.31); 0.90, 0.50, and 0 for switchers from GA to IFNB (GA/IFNB, n = 18; P = 0.19; P = 0.01); 0.50, 0.68, and 0 for switchers from an IFNB to another IFNB (IFNB/IFNB’, n = 71; P = 0.34; P = 0.02). Estimated relapse-free proportion after 24 months of treatment was 42% (95%CI=15–66%) during the period on IFNB versus 53% (95%CI = 17–80%) on GA for IFNB/GA ( P = 0.21); 12% (95%CI = 0–40%) on GA versus 87% (95%CI = 59–97%) on IFNB for GA/IFNB ( P = 0.001); and 41% (95%CI = 29–52%) on initial IFNB versus 67% (95%CI = 53–79%) on subsequent IFNB for IFNB/IFNB’ ( P = 0.0001). Conclusions Switching first-line DMT in patients with RRMS failing initial therapy may be effective in many cases.

scholarly journals P.051 Patient-reported adverse events on Multiple Sclerosis disease-modifying therapies in an urban tertiary MS clinic

2016 ◽  
Vol 43 (S2) ◽  
pp. S33-S33
Author(s):  
ZJ Liao ◽  
L Lee ◽  
K Carr
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Real Life ◽  
Retrospective Chart Review ◽  
First Line ◽  
Disease Modifying Therapies ◽  
Multiple Sclerosis Disease ◽  
Patient Reported ◽  
Disease Modifying ◽  
The Impact

Background: Disease-modifying therapies (DMT) have been shown to reduce relapses and delay disability in individuals with relapsing-remitting multiple sclerosis (MS). However, these medications can cause adverse events (AE) leading to poor adherence. To better understand their clinical utility, this study examined real-life experiences with DMT in a tertiary MS clinic. Methods: A retrospective chart review (1999-2015) was conducted to evaluate the prevalence of AE and discontinuation rates of Health Canada approved DMT. Results: 445 MS patients who have used at least one DMT in their lifetime were reviewed. Among first-line injectable therapies, interferon beta (IFNβ) 1-α IM users (49.6%) were most likely to report an AE. Flu-like reactions and injection site reactions were the most commonly reported AE. Among first-line oral therapies, BG-12 users (58.5%) were most likely to report an AE. The most common AE were flushing and gastrointestinal upset. DMT that were most frequently discontinued as a result of AE were IFNβ 1-α SC (39.3%), IFNβ 1-α IM (36.8%) and BG-12 (34.6%). Conclusions: The prevalence of AE and discontinuation rate were congruent. In comparison with recent literature, this study demonstrated lower prevalence of AE but equivocal or higher discontinuation rates. This discrepancy could represent a more realistic depiction of the impact that DMT AE have on patients.

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