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[Formula presented] [Formula presented] Fig. 1. Impact des anti-CD20 sur le risque de COVID-19 severeCopyright © 2023
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Introduction Les traitements anti-CD20 (rituximab-ocrelizumab) sont associés à une augmentation du risque de formes sévères de COVID-19 chez les patients vivants avec une sclérose en plaques (pvSEP), mais on ignore si cette association est due à un biais de confusion en lien avec le handicap neurologique préexistant et si l'impact de ces traitements dépend ou non de la forme progressive ou récurrente-rémittente de la maladie. L'objectif était d'évaluer l'impact des thérapies anti-CD20 sur la sévérité du COVID-19 chez les patients atteints de SEP rémittentes (pvSEP-R) et progressive (pvSEP-P), au sein de la cohorte rétrospective COVISEP (pvSEP avec COVID-19). Méthodes Les critères d'inclusion étaient : pvSEP;COVID-19;traitement de fond de haute efficacité (fingolimod-natalizumab-rituximab-ocrelizumab) pour les pvSEP-R;âge<70 ans et score EDSS≤8 pour les pvSEP-P (ces caractéristiques correspondent au profil des pvSEP-R et pvSEP-P susceptibles de recevoir un traitement anti-CD20). L'impact des anti-CD20 sur la sévérité du COVID-19 (≥hospitalisation avec oxygénothérapie) a été évalué séparément chez pvSEP-R et pvSEP-P par régression logistique pondérée par score de propension. Des analyses en sous-groupes prévues a priori ont été réalisées selon le statut vaccinal, le sexe, le score EDSS et l'âge. Résultats Au total, 971 pvSEP-R (43 % sous anti-CD20) et 429 pvSEP-P (52,7 % sous anti-CD20) ont été analysés. Chez les pvSEP-R, les anti-CD20 étaient associés à un surrisque de COVID-19 sévère (OR 5,29 IC95% [2,81;9,95]), retrouvé aussi chez les patients vaccinés (8,74 [1,12;68,23]). Chez les pvSEP-P, les anti-CD20 n'était pas associés au COVID-19 sévère (1,28 [0,76;2,15]). Dans les analyses en sous-groupe chez les pvSEP-P, le surrisque était retrouvé chez les pvSEP-P avec EDSS <6 (3,89 [1,39;10,9]) et <54 ans (3.00 [1,14;7,94]) (figure 1). Conclusion Les anti-CD20 augmentent le risque de COVID-19 sévère chez les pvSEP-R, y compris chez les patients vaccinés. En revanche, ces traitements ne sont pas associés à un surrisque de COVID-19 sévère chez les patients pvSEP-P. Le handicap neurologique et l'âge interagissent négativement avec l'exposition aux anti-CD20 sur le risque de COVID-19 sévère chez les pvSEP-P. Mots clés Sclérose en plaques , COVID-19 , Traitement anti-CD20 Déclaration de liens d'intérêts E Januel rapporte le remboursement de frais d'inscription en congrès, de voyage et d'hébergement par Sanofi Genzyme, aucun en rapport avec le présent travail. C. Louapre a reçu des fonds de voyage et/ou des honoraires de conférencier de Biogen, Novartis, Roche, Sanofi, Teva et Merck Serono, aucun en rapport avec le présent travail. C. Papeix a reçu des fonds de voyage et/ou des honoraires de conférencier de Novartis, Biogen, Teva, Roche, Merck et Biogen Idec, aucun en rapport avec le présent travail. Les autres auteurs ne signalent aucun conflit d'intérêt.
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Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets.Copyright © 2023
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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.
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Introduction: Since the beginning of the COVID-19 pandemic, national and international registries of COVID-19 in patients with multiple sclerosis (MS) identified the most important risk factors for developing a severe form of COVID-19, mainly defined by oxygen-dependent pneumonia, and in the most severe cases the need for ventilation or death. Objective(s): to provide an overview of what we have learned about COVID-19 in patients with MS over the past 2 years Results: Although the majority of patients who died from COVID- 19 were patients with high neurological disability or other severe co-morbidities, anti-CD20 therapy was rapidly identified as a factor associated with worse prognosis of COVID-19, unlike other MS disease modifying therapies. A recent analysis of the COVISEP registry (2635 COVID-19 cases in patients with MS) with propensity scores found that this deleterious effect of anti-CD20 was predominant in the relapsing-remitting group only. This higher risk of severe COVID-19 associated with anti-CD20 therapy has led to prioritising patients on anti-CD20 for access to anti-COVID treatments, either pre-exposure or in case of infection. Anti-CD20 therapy has also been associated with a decreased humoral response after infection and an increased risk of postvaccination infection. With new Omicron variant subtypes and the advent of vaccination, the symptoms of COVID-19 and their severity have been largely modified, with severe forms becoming rarer. Conclusion(s): Overall, the therapeutic decision strategy for MS has been little changed in the era of COVID-19, given the major benefit of high efficacy therapies in relapsing remitting MS, but therapeutic choices in progressive patients must weigh the increased risk of severe COVID-19 in patients with higher disability against the modest therapeutic efficacy of approved or off-label treatments for progressive MS.
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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.
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Background: Outcomes of coronavirus disease 2019 (COVID- 19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibodyassociated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. Objectives: The objective was to describe the clinical characteristics and outcomes of COVID-19 in patients with neuromyelitis optica and associated disorders and to identify the factors associated with COVID-19 severity. Methods: We conducted a multi-center, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020 and June 30th, 2020. Main outcome was COVID-19 severity score assessed on a 7-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). Results: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower EDSS score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]). Conclusions: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19, however we recommend to maintain preventive measures to limit the risk of contamination with SARS-CoV-2 in this immunocompromised population.
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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.