ABSTRACT
Background: The COVID-19 pandemic continues to challenge neurologists in counselling patients with multiple sclerosis (pwMS) regarding SARS-CoV-2,disease-modifying treatment (DMT) and vaccination. Objective(s): To characterize and describe predictors ofCOVID-19 outcomein pwMS in a nationwide population-based study. Method(s): We included pwMS with a PCR-confirmed diagnosis of COVID-19 established between January 1st, 2020 and December 31st, 2021. COVID-19 course was classified as either mild, severe or fatal. Impact of DMT, specifically antiCD20 monoclonal antibodies (ocrelizumab or rituximab), and vaccinationon COVID-19 outcome was determined by multivariable models adjusted for a-priori-risk (determined by a cumulative risk score comprising age and comorbidities). Result(s): Of 228 pwMS with COVID-19 (mean age 43.0 years [SD 12.6], 72.4% female, median EDSS 1.5 [range 0-8.5], 73.1% on DMT [15% on antiCD20]), 90.3% had a mild course and 9.7% a severe course with 3.1% dying from COVID-19. A-priori-risk robustly predicted COVID-19 severity (R20.714;p<0.001). Adjusting for a-priori-risk, antiCD20 treatment was associated with increased COVID-19 severity (odds ratio [OR] 3.1;95% CI: 1.2-11.8;change inR20.092;p=0.002), but exposure to any other DMT was not. In the registry, 27 patients were fully vaccinated (21 BioNtech-Pfizer, 3 Moderna, 3 Astra-Zeneca;21 on DMT, 4 on antiCD20) withSARS-CoV-2infection occurring after a median 4 months from vaccination (range 1-9). COVID-19 course was mild in 100% of vaccinated pwMS compared to only 86% in the unvaccinated group. Conclusion(s): In a population-based MS cohort, COVID-19 course is primarily predicted byage and comorbidities (explaining about 70% of variance). AntiCD20 treatment is associated with a moderately increased risk, while reassuringly vaccination provides protection from severeCOVID-19. All pwMS should be vaccinated and DMT decisions should then be focused on treating MS rather than the pandemic.
ABSTRACT
Introduction: Booster vaccination against SARS-CoV-2 is recommended for patients with multiple sclerosis (pwMS), usually six months after the last vaccination. Objectives and aims: To investigate humoral response after SARS-CoV-2 booster vaccination in pwMS compared to healthy controls (HC), as well as the role of the third vaccination in the primarily seronegative and therefore more vulnerable group of treated pwMS (S1PMs, anti-CD20 mAbs). Method(s): In this prospective multicenter study on 292 pwMS and 46 HC, who had all received two vaccinations, SARS-CoV-2 IgG response was measured in the month before and 2-4 months after booster vaccination. PwMS were categorized as follows: untreated (N-DMT, n=32), receiving disease-modifying therapy (DMT) with expected humoral response (er-DMT: interferon-beta preparations, glatiramer acetate, dimethyl fumarate, teriflunomide, natalizumab, cladribine, alemtuzumab;n=120) or no expected humoral response (nr-DMT: S1PMs, CD20mAb;n=140). Result(s): PwMS on nr-DMT had significantly lower median antibody levels before (12.1 U/ml [0.4-2500]) and after booster vaccination (305 U/ml [0.4-2500]) in comparison to other groups (p<0.001). We did not find differences in antibody levels after homologous (n=281;2500 [0.4-2500]) and heterologous (n=57;2500 [0.4-2500]) vaccination regime regardless of the DMT group. The DMT group (= -0.16;95% CI -34.88, -5.08;p=0.009) were associated with antibody levels after booster vaccination, while time to revaccination(6 months [1-13]) was not. After booster vaccination, seropositivity was reached in 75.8% and 82.2% of pwMS on anti-CD20 mAbs and S1PMs, respectively. Complete B-cell depletion significantly decreased the probability of seroconversion even after the third vaccination (OR 0.14;p=0.021), whereas time interval to last DMT intake and time to revaccination did not. Twenty-three patients reported a SARSCoV- 2 infection (3 N-DMT, 10 er-DMT, 10 nr-DMT), one being asymptomatic and the rest having a mild course. Conclusion(s): Humoral response to SARS-CoV-2 booster vaccination in pwMS is excellent. While reduced by S1PMs and CD20mAb, protective response is still expected in the majority of patients.
ABSTRACT
Background and aims: Booster vaccination against SARSCoV- 2 is recommended for everyone approximately six months after the last vaccination, including for patients with multiple sclerosis (pwMS). Methods: In this prospective single-center study on 171 pwMS and 38 healthy controls (HC), who had all received two vaccinations, SARS-CoV-2 IgG response was measured in the month before and 2-4 months after booster vaccination. PwMS were categorized as follows: untreated (N-DMT, n=17), receiving DMT with expected humoral response (er-DMT: all but S1PM and CD20mAB;n=65) or no expected humoral response (nr-DMT: S1PM, CD20mAb;n=89). Results: Absolute antibody levels (median 253.5 U/ml [range 0.4-2500]) before booster vaccination were similar between HC (516 [49.5-2500]), N-DMT (648 [0.4-2345]) and er-DMT (858.5 [25.6-2500]), while nr-DMT had significantly lower antibody levels (32.8 [0.4-2500];p<0.001). After booster vaccination, the absolute antibody levels were as follows: HC (2500 [2190-2500]), N-DMT (2500 [32.2-2500]), er-DMT (2500 [1951-2500]), and nr-DMT (548 [0.4-2500];p<0.001). We did not find differences in antibody levels after homologous (n=96;2500 [0.4-2500]) and heterologous (n=53;2500 [0.4- 2500]) booster vaccination. Time to revaccination (6 months [1-10] was not associated with antibody level. Four of 13 (30.8%, all CD20mAb) seronegative pwMS remained seronegative after booster vaccination. Seven patients reported a SARS-CoV-2 infection (1 N-DMT, 6 nr-DMT). Efficacy rate for preventing hospitalization or death was 100% in all groups. Conclusion: Humoral response to SARS-CoV-2 booster vaccination in pwMS is excellent. While reduced by immunosuppressive DMT, protective humoral response is still expected in the majority of patients.
ABSTRACT
Background and aims: Social distancing measures during the Covid-19 pandemic reduced access to health care and concerns were raised over the safety of immunosuppressive disease modifying treatments (DMT) for multiple sclerosis (MS). Here, we aimed to investigate changes in DMT prescription before and during the pandemic in a large and well-characterized real-world cohort of MS patients. Methods: From the Vienna MS database (VMSD) we extracted MS patients who were initiated on a new DMT (both treatment-naïve and switching) between January 1st 2017 and December 31st 2021. Two time periods were defined: 1) the preCovid-19 era (January 1st 2017 to March 15th 2020, i.e. the day of the first lockdown in Austria) and the Covid-19 era (March 16th 2020 to December 31st 2021). Average annualized DMT prescription rates were descriptively compared between the two periods. Results: The average annualized number of prescriptions in the preCovid-19 era was 90.3/year and dropped to 74.8/year (-17.2%) in the Covid-19 era, driven by a marked reduction to 41.7/year (-54%) in the first nine months of the Covid-19 era, partly offset by a rise to 101 in 2021. Use of alemtuzumab (-64%), antiCD20 (-49%), cladribine (-46%), and S1PM (-38%) was reduced, while natalizumab increased by 24%. Lower efficacy treatments remained stable. Conclusion: The pandemic coincides with a drop in DMT prescription, most markedly for immunosuppressive highefficacy treatments, strongly suggesting the pandemic as the causal factor. If and how much this affects long-term outcome is yet to be determined. (Figure Presented).
ABSTRACT
Objective: To evaluate feasibility of remote visits in people with MS (pwMS). Background: Disease monitoring in multiple sclerosis (MS) includes periodic visits to treating neurologists (MSologists) for a clinical and paraclinical examinations. In light of the recent Coronavirus pandemic, there is an urgent need to develop and implement strategies for remote patient monitoring using telemedicine. Design/Methods: We randomized 45 pwMS into three groups that determined the modality of their next scheduled visit: (i) regular outpatient visit, (ii) a visit over the phone or (iii) a visit by means of video chat. Baseline disease characteristics included clinical information (EDSS, treatment, disease duration) and patient reported outcomes (Multiple Sclerosis Impact Scale, MSIS). As the primary endpoint, non-inferiority of telemedical visits (groups ii and iii) was determined based on mean scores on the TMPQ (Telemedicine Physician Satisfaction Questionnaire: min: 17 and max: 85 points) at follow up compared to regular visits (group i). The secondary endpoint consisted of physician satisfaction with the single visits based on the PPSM (Patient and Physician Satisfaction) score (min: 6 and max: 36 points). Results: 42 pwMS completed this study. The mean (SD) age was 34 (8) years, median EDSS was 0 (range: 0-6). The mean (SD) disease duration was 6 (2.4) years. Satisfaction with the telemedical visits (groups ii and iii) was non-inferior compared to regular visits (group i). Mean (SD) TMPQ scores were 73 (4.3) in the regular visit group, 79 (3.9) in the telephone visit group, and 76 (3.7) in the video chat group. Physician satisfaction was similar for all three groups. PPSM scores were 32 (3.3) in the regular visit group, 32 (2.7) in the telephone visit group, and 34 (1.8) in the video chat group. Conclusions: In this randomized controlled trial, single tele-visits for pwMS were not inferior to regular visit determined by patient and physician satisfaction.
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Background: Vaccination against SARS-CoV2 is unanimously recommended for patients with multiple sclerosis (MS), although some disease-modifying treatments (DMT) might limit immune response. However, data informing on differences in efficacy and safety of available vaccines in MS patients are scarce. Objective: To compare magnitude and success rate of humoral immune response and safety of SARS-CoV-2 vaccines in patients with MS and healthy individuals. Methods: In this multicenter prospective observational study on 467 MS patients and 124 healthy controls, SARS-CoV-2 IgG response was measured using anti-spike protein-based serology 3 months after the first dose. The primary endpoint was defined as the proportion of patients developing protective antibodies, secondary endpoints included antibody titer, efficacy and safety parameters. Results: Preliminary analyses show that 89.9% of MS patients developed protective levels of anti-SARS-CoV-2 IgG antibodies compared to 97.6% in healthy controls. Positivity rate in patients on immunosuppressive DMT (sphingosine 1 receptor modulators [S1PM], antiCD20 monoclonal antibodies [CD20mAb], cladribine) was significantly lower (63.8%, p<0.001) than in patients without DMT (91.7%) or on immunomodulatory DMT (92.9%;interferon beta, glatiramer acetate, dimethyl fumarate, teriflunomide). Specifically, seroconversion was lowest under CD20mAb (55.2%) followed by S1PM (75%). Detailed analyses reporting antibody titer levels and role of vaccine type, as well as influence of baseline lymphocyte count, time interval from last DMT dosing, vaccine efficacy and safety parameters will be reported at ECTRIMS 2021. Conclusions: Humoral response to SARS-CoV2 vaccines in MS patients is generally excellent. While reduced by immunosuppressive DMT, most importantly by B-cell depleting CD20mAb, protective humoral response is still expected in the majority of patients.
ABSTRACT
Background: The COVID-19 pandemic challenges neurologists in counselling patients with multiple sclerosis (pwMS) with respect to their risk for and by SARS-CoV-2 and in guiding disease-modifying treatment (DMT). Objective: To characterize the prevalence, severity and overall mortality of SARS-CoV-2 infections in pwMS specifically associated with different DMT in a nationwide population-based study. Methods: We included patients aged ≥18 years with a confirmed diagnosis of MS and a diagnosis of COVID-19 established between January 1, 2020 and April 30, 2021. We classified COVID-19 course as either mild, severe or fatal. Impact of DMT and specifically immunosuppressants (alemtuzumab, cladribine, fingolimod, ocrelizumab or rituximab) on probability of severe or fatal COVID-19 was determined by multivariable models, adjusted for a-priori-risk estimated by a recently developed score (comprising age, comorbidities, and degree of disability). Results: Of 171 MS patients with COVID-19 (mean age 43.2 years [SD 13.4], 71% female), 86.0% had a mild course, 9.4% a severe course and 3.5% died from COVID-19. A-priori-risk significantly predicted COVID-19 severity (R2 0.814;p<0.001) and mortality (R2 0.664;p<0.001). Adjusting for this a-priori-risk, neither exposure to any DMT nor exposure to specific immunosuppressive DMT were significantly associated with COVID-19 severity (odds ratio [OR] 1.6;p=0.667 and OR 1.9;p=0.426) or mortality (OR 0.5;p=0.711 and 2.1;0.233). Conclusions: In a population-based MS cohort, COVID-19 severity and mortality were independent of exposure to DMT and immunosuppressive DMT when accounting for other already known risk factors. This provides reassuring evidence that COVID-19 risk can be individually anticipated in MS and-except for a very small proportion of high-risk patients-treatment decisions should be focused on treating MS rather than the pandemic.