ABSTRACT
Introduction: Nowadays, mandatory vaccination in patients with multiple sclerosis (MS) is widely recommended. Regarding COVID19, the absence of specific warnings led to the proposal of vaccination in patients with inflammatory diseases of the central nervous system. However global vaccination hesitancy remains and potential effect of COVID19 vaccination on disease activity needs to be assessed. Objective(s): We aimed to evaluate if COVID19 vaccination or infection increased the risk of clinical conversion to multiple sclerosis or evidence of disease activity (EDA) in a cohort of RIS subjects. Method(s): This multicentric observational study is based on the RISC cohort. Data regarding COVID19 infection and vaccination has been collected between January 2020 and December 2021. We compared the occurrence of clinical conversion to MS and EDA in patients according to their vaccination status. The same analysis was conducted by comparing patients according to their history of COVID19 infection. Result(s): 217 subjects with known vaccination status were included (Mean age: 44yrs, F/M sex ratio 2.7). 80% of subjects had a complete vaccination and 20% were incompletely or not vaccinated. Both groups did not differ regarding the main demographical data and known risk factors of conversion to MS. No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (2.4% versus 2.5%, p = 0.9747). We did not observe any statistical difference regarding the rate of EDA in both groups. 20% of subjects had a history of COVID-19 infection. The rate of clinical conversion to MS in the infected compared to the noninfected group did not show any difference The global conversion rate to MS in the whole RISC cohort in 2021 was 2.64%, which is comparable with the observed rates during the four previous years (5.75%, 2.55%, 4.79%, and 4.85% per year respectively). Conclusion(s): Our study suggests that COVID19 vaccination does not increase the risk of clinical conversion to MS in RIS subjects and supports that immunization can be safely proposed for these patients.
ABSTRACT
Introduction: Natalizumab (NTZ) is a widely used second-line treatment for multiple sclerosis (MS), administered with a fourweeks infusion interval. Extending the interval between two infusions could reduce the economic costs of this therapy, the incidence of rare side effects such as progressive multifocal leukoencephalopathy and improve the patients' quality of life with less frequent day-hospitalizations. Aim(s): At the Fondation Rothschild Hospital in Paris, for sanitary reasons during COVID-19 lockdown, patients were systematically switched to a 6-weeks NTZ extended-interval dosing (EID) from April 2020 to the present day. In this monocentric retrospective study, we aimed at evaluating the clinical and radiological efficacy of NTZ EID compared to the 4 weeks standard-interval dosing (SID) in adult patients with active MS. Method(s): We screened the local pharmacy database for NTZ administration and included all adult patients diagnosed with MS and treated with NTZ for at least 6 months with a SID, before being treated with an EID for at least 12 months. Data about disease activity, treatments received, MRI and clinical data were retrospectively collected from the local French MS observatory (OFSEP) database. The primary outcomes were the incidence of MS attacks, new MRI lesions or the presence of gadoliniumenhancing lesions during NTZ SID or EID. Result(s): A total of 49 patients were included for final analysis. 21 (42.9%) were male, with a median MS duration from the first symptom to NTZ introduction of 60 [30, 110] months. Patients were treated for a median time of 34.6 [15.1, 72.4] months by a SID, followed by a median time of 18.6 [14.7, 20.6] months by an EID. The mean EDSS before EID was 2.0 [1.5, 3.0] and 1.5 [0.0, 2.8] during EID. During natalizumab SID, one patient (2%) presented a new MS attack, 5/45 patients (11%) had new MRI lesions, with gadolinium enhanced lesions in 1/45 (2%) patient. This did not differ significantly during natalizumab EID where no MS attack were observed (p = 1), new MRI lesions were present in 1/41 (2%) patient and no gadolinium-enhancing lesion was found. Patients were followed for a median time of 130 [78, 205] months in total. Conclusion(s): We did not observe more clinical attacks or MRI activity signs when extending the interval between NTZ infusions from 4 to 6 weeks. Data from randomized controlled trials are needed to allow better consideration of side-effects and safety.
ABSTRACT
Introduction: SARS-CoV-2 seroconversion rate after COVID-19 may be influenced by disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMO-SD). Objectives: To investigate the seroprevalence and the quantity of SARS-CoV-2 antibodies in a cohort of patients with MS or NMO-SD. Aims: To improve our knowledge of the impact of different DMTs on the immune response to SARS-COV2. Methods: Blood samples were collected in patients diagnosed with COVID-19 between February 19, 2020 and February 26, 2021. SARS-CoV-2 antibody positivity rates and Ig levels (anti-S IgG titer, anti-S IgA index, anti-N IgG index) were compared between DMTs groups. Multivariate logistic and linear regression models were used to estimate the influence of DMTs and other confounding variables on SARS-CoV-2 serological outcomes. Results: 119 patients (115 MS, 4 NMO, mean age: 43.0 years) were analyzed. Overall seroconversion rate was 80.6% within 5.0 (SD 3.4) months after infection. 20/21 (95.2%) patients without DMT and 66/77 (85.7%) patients on DMTs other than anti-CD20 had at least one SARS-CoV-2 Ig positivity, while this rate decreased to only 10/21 (47.6%) for patients on anti-CD20 (p < 0.001). Patients on anti-CD20 had a lower anti-S IgG titer (mean [SD], 1.4 [1.6]) relative to patients on other DMTs (2.4 [1.1]) or no DMT (2.7 [0.8] (p<0.001 by ANOVA). Being on anti-CD20 was associated with a decreased odd of positive serology (OR, 0.06 [95%CI, 0.01-0.59], p=0.01) independently from time to COVID-19, total IgG level, age, sex and COVID-19 severity. Time between last anti-CD20 infusion and COVID-19 was longer (mean [SD], 3.7 [2.0] months) in seropositive patients compared to seronegative patients (mean [SD], 1.9 [1.5] months, p=0.04). Serological data at 6 months follow-up after inclusion will be available and presented during the congress. Conclusions: SARS-CoV-2 antibody response was decreased in patients with MS or NMO-SD treated with anti-CD20 therapies. Monitoring long-term risk of reinfection and specific vaccination strategies in this population may be warranted.
ABSTRACT
Background and aims: Patient satisfaction and quality of life improvement is important to ensure persistence with treatment. In PRO-MSACTIVE (NCT03589105) phase IV study, evaluating ocrelizumab (OCR), patients with active relapsing multiple sclerosis (RMS) were administered selfreported patient reported outcomes (PROs) questionnaires. We report the interim analysis of PROs data. Methods: In PRO-MSACTIVE, patients receive OCR infusions for a 48-weeks treatment period. Efficacy and safety were assessed and several PROs questionnaires were self-administered prior to the administration of OCR: MS symptom severity scale (SymptoMScreen), Modified Fatigue Impact Scale (MFIS), EuroQol 5-Dimension Questionnaire (EQ-5D-5L with VAS), Work Productivity and Activity Impairment scale (WPAI:SHP), Multiple Sclerosis International Quality of Life Questionnaire (MusiQoL) and Treatment Satisfaction Questionnaire (TSQM-14). Results: PRO-MSACTIVE has enrolled 422 patients in France (female 73.7%;mean (SD) age 39.7 years (10.5);25.1% naïve of previous DMT;mean (SD) baseline EDSS 2.80 (2.04)). This interim analysis included data at W48 from 335 patients who have completed their treatment period before COVID-19 lockdown. Improvement from baseline total mean (SD) scores were observed for SymptoMScreen (-1.3 (8.8)), MFIS (-2.9 (13.47)), EQ-5D-5L with VAS health state score (+4.07 (17.02)), WPAI:SHP activity impairment (-5.31 (23.65)), MusiQoL (+1.52 (11.0)) and TSQM-14 (+8.13 (21.39)). TSQM-14 total mean (SD) score improved from 59.7 (19.69) to 68.55 (20.03). The largest improvements from baseline were observed for MusiQoL on the psychological wellbeing, coping and activities of daily living domains. EDSS score was improved (<-0.5) or stable (-0.5;+0.5) for 85.4% of patients. Conclusion: In PRO-MSACTIVE, patients with active RMS reported improvement in PROs from baseline to W48.
ABSTRACT
Background: Risk factors associated with the severity of COVID- 19 in patients with multiple sclerosis (MS) begin to be identified from several cohort studies. Disease modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objectives: The objective was to describe the clinical characteristics and outcomes in patients with COVID-19 and to identify the factors associated with COVID-19 severity. Methods: This multicenter, retrospective, observational cohort study (COVISEP registry, NCT04355611) included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020 and July 14, 2020. The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1: not hospitalized, no limitations on activities, to 7: death;cutoff at 3: hospitalized, not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Score (EDSS), comorbidities, COVID-19 characteristics and outcome. Univariate and multivariate logistic regression models were used to estimate the influence of collected variables on COVID-19 outcome. Results: A total of 405 patients (mean age: 44.7 years, female/male: 293/112, mean disease duration: 13.4 years) were analyzed. Seventy-eight patients (19.3%) had a COVID-19 severity score ≥ 3, and 12 patients (3.0%) died from COVID-19. Median EDSS was 2.0 (range: 0-9.5), 326 patients (80.5%) were on DMT. There was a higher proportion of patients with COVID-19 severity score ≥ 3 among patients with no DMT relative to patients on DMTs (39.2% versus 14.4%, p<0.001). Multivariate logistic regression models determined that age (OR for 10 years: 1.8, 95% CI: 1.4-2.4), EDSS (OR for EDSS ≥ 6: 4.5, 95% CI: 2.0-10.0) were independent risk factors for COVID-19 severity score ≥ 3 (hospitalization or higher severity) while immunomodulatory treatment (interferon or glatiramer acetate) was associated with lower risk of COVID-19 severity score ≥ 3 (OR: 0.2, 95% CI: 0.05-0.8). EDSS was associated with the highest variability of COVID-19 severe outcome (R2= 0.18), followed by age (R2= 0.06) and immunomodulatory treatment (R2= 0.02). Conclusions: EDSS and age were independent risk factors of severe COVID-19, while exposure to immunomodulatory DMTs (interferon and glatiramer acetate) were independently associated with lower COVID-19 severity. We did not find an association between other DMTs exposure (including immunosuppressive therapies) and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of MS patients during the COVID- 19 pandemic.