ABSTRACT
Background and goals: The goal of this study was to assess the rate of self-reported side effects, need for medical assistance and hospitalizations after a third COVID-19 vaccination in people with multiple sclerosis (pwMS) with or without disease-modifying treatments. We also wanted to investigate if SARS-CoV2 antibody levels correlate with side effects. Method(s): Participants enrolled in the vaccination trial Nevrovax were invited to complete a questionnaire on side effects after the third dose of SARS-CoV-2 vaccination. SARS-CoV2 antibodies were measured in BAU/mL after 3 weeks or longer after vaccination. The results were linked to data from the Norwegian Immunization Registry. Statistical analyses were performed using SPSS Stastistics version 26. Group comparisons were analyzed using independent samples t-tests and chi-square tests with a significance level of 0.05. Result(s): In total 606 pwMS (77.4% female, mean age 48.3 years) were included in this study. At the time of immunization, 61.7% of all pwMS were treated with anti-CD20 monoclonal antibodies and 19%with sphingosine 1-phosphate receptor modulators. Mean time to follow up from third dose to answering the questionnaire was 29.9 days.586 patients received an mRNAvaccine (257 BNT162b2 and 344 mRNA1273 as dose 3) while 20 received a viral vector vaccine-AZD1222 (One as dose 3). Data on vaccine type of dose 3 was missing in 4 patients. Side effects were reported by 66.2% of all pwMS. Mean age of patients with and without side effects were 47.0and 50.7 years, respectively (p < 0.01). We found a higher rate of side effects among women (68.8%) than men (59.1%) (p=0.047), and a higher rate among those using anti-CD20 therapy (73.3%) (p<0.05). Blood samples of SARS-CoV2 antibodies were obtained in 547 patients. There were no significant difference in antibody levels in patients with side effects (mean 1185 BAU/ mL) and patients without side effects (mean 1174 BAU/mL), p= 0.66. 16 pwMS (2.6%) sought medical help after vaccination. No pwMS needed hospitalization. Conclusion(s): Our results demonstrate that a third dose of SARSCov2 vaccines are safe in pwMS using different DMTs. Rate and severity of side effects vary with both treatment and demographic factors. SARS-CoV2 IgG levels did not correlate with side effects. There were no hospitalizations after vaccination with a 3rd dose.
ABSTRACT
Introduction: Expert organizations worldwide recommend that all patients with multiple sclerosis (MS) should be vaccinated against acute respiratory syndrome coronavirus 2 disease of 2019 (COVID- 19). However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. There is increasing evidence of altered protective humoral immunity after mRNA-COVID-19 vaccines among patients treated with fingolimod, rituximab and ocrelizumab. However, the role of cellular immunity is still unknown. Appropriate knowledge regarding the development of protective immunity is of paramount importance in respect to medical, political and public health measures to aid the fight against the COVID-19 pandemic. Objectives and Aims: We aimed to characterize humoral and cellular immunity after mRNA-COVID-19 vaccines in patients with MS treated with high-efficacy DMTs (NEVROVAX). Methods: All patients treated with alemtuzumab, natalizumab, fingolimod, rituximab or cladribine, and vaccinated with BNT162b2- or mRNA-1273-COVID-19 vaccine were invited. We assessed protective humoral immunity by measuring acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG response using anti-spike protein-based serology in all included patients before, and 3-6 weeks after full vaccination (NEVROVAX-HUMORAL). Cellular immunity was investigated using high dimensionality multiparameter analyses in 50 pre-selected individuals (10 patients in each treatment group;NEVROVAX-CELLULAR) and in all patients not developing protective humoral immunity in the former group (NEVROVAX-EXTENSION). Results and Conclusions: Over 900 patients were invited and, to date, more than 300 patients have been included in our study. Preliminary results show altered protective humoral immunity in MS patients treated with rituximab and fingolimod. Continuous analysis of cellular immunity is conducted in these patients. The percentage of vaccinated inhabitants in Norway is still under 10%. We expect to complete all analyses by September 2021 and will present our results during ECTRIMS 2021.
ABSTRACT
Background: Both induction therapy, like oral cladribine, and B-cell depletion therapy, like rituximab, are highly effective disease modulatory treatments (DMTs) in relapsing multiple sclerosis (MS). The high economic costs of the registered DMTs may limit availability of treatment and strain health budgets worldwide. Oral cladribine is a recently approved DMT in Europe, while rituximab is used off-label, especially in Norway and Sweden. Large observational studies indicate good tolerance and treatment effects in MS and studies from other diseases indicate a good safety profile. However, to our knowledge, no phase three studies have compared rituximab with any established highly effective DMT. Formal safety data is also lacking for rituximab treatment in MS. Objectives: To perform a prospective randomized open-label blinded endpoint multicenter non-inferiority study. The primary objective is to test whether rituximab is non-inferior to oral cladribine for treatment of relapsing MS. Methods: In total 264 MS patients with relapsing MS will be recruited from 11 Norwegian centers and followed for 96 weeks. Inclusion criteria are having a relapsing MS diagnosis, age 18-65 years, at least one clinical relapse or one new T2 lesion on MRI within the last year and willingness to use contraception during the study period. Exclusion criteria are contraindications to either treatment, previous use of either or a similar treatment, or treatment with fingolimod or natalizumab (due to risk of rebound activity) within the last six months. The study participants will be treated with either cladribine or rituximab according to current guidelines. Results: The primary endpoint is difference in number of new or enlarging T2 lesions between the two groups from rebaseline at 12 weeks to the end of the study at 96 weeks. Furthermore, we will study clinical course, blood samples and MRI biomarkers to provide tools for personalized MS treatment. Finally, the health economic consequences of these treatment options will be evaluated. At the time of abstract submission, 55 patients have been included across three study sites. The Covid19 outbreak unfortunately resulted in a temporary halt in inclusion from March to May 2020, but the study has now been reopened. End of study is estimated to fall 2023. Conclusions: This study will guide clinicians and patients in future treatment choices for MS. The results will provide valuable knowledge concerning treatment strategies and can potentially have a huge impact on the costs of future MS treatments.