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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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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.