Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of ...developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities.
To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity.
The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020.
COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms.
The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 not hospitalized with no limitations on activities to 7 death) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes.
A total of 347 patients (mean SD age, 44.6 12.8 years, 249 women; mean SD disease duration, 13.5 10.0 years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 95% CI, 1.4-2.5), EDSS (OR for EDSS ≥6, 6.3 95% CI. 2.8-14.4), and obesity (OR, 3.0 95% CI, 1.0-8.7) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01).
In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.
Introduction
Natalizumab, a therapy for relapsing–remitting multiple sclerosis (RRMS), is associated with a risk of progressive multifocal leukoencephalopathy (PML). Over the last several years, ...practitioners have used off-label extended interval dosing (EID) of natalizumab to reduce PML risk, despite the absence of a large-scale efficacy evaluation.
Methods
We conducted a retrospective, multicenter cohort study among adults with RRMS receiving stable standard interval dosing (SID), defined as a ≥ 12-month consecutive period of ≥ 11 natalizumab infusions/year in France. We compared the 12-month risk difference of remaining relapse-free (primary endpoint) between patients who switched to EID (≤ 9 natalizumab infusions) and those who remained on SID, with a noninferiority margin of − 11%. We used propensity score methods such as inverse probability treatment weighting (IPTW) and 1:1 propensity score matching (PSM). Secondary endpoints were annualized relapse rate, disease progression, and safety.
Results
Baseline characteristics were similar between patients receiving EID (
n
= 147) and SID (
n
= 156). The proportion of relapse-free patients 12 months postbaseline was 142/147 in the EID (96.6%) and 144/156 in the SID group (92.3%); risk difference (95% CI) 4.3% (− 1.3 to 9.8%);
p
< 0.001 for non-inferiority. There were no significant differences between relapse rates (0.043 vs. 0.083 per year, respectively;
p
= 0.14) or Expanded Disability Status Scale mean scores (2.43 vs. 2.72, respectively;
p
= 0.18); anti-JC virus index values were similar (
p
= 0.23); and no instances of PML were reported. The comparisons using IPTW (
n
= 306) and PSM (
n
= 204) were consistent.
Conclusion
These results support the pertinence of using an EID strategy for RRMS patients treated with natalizumab.
Clinical Trials
gov identifier (NCT04580381).
Background:
Counseling on pregnancy is still challenging, particularly regarding the use of disease-modifying treatments (DMTs). We are lacking long-term outcomes in children exposed to DMTs.
...Objectives:
This study aimed to set up a French pregnancy registry for women with multiple sclerosis (MS) and related disorders nested within the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort.
Methods:
Prospective, observational, multicentric, epidemiological study in France. Neurological visits are organized according to routine practice. Data are collected on the OFSEP minimal datasheet. Auto-questionnaires on pregnancy are completed by patients at Months 5–6 and 8 during pregnancy, and Months 3, 6, and 12 postpartum. A specific survey on analgesia is completed by anesthesiologists. Pediatric data are collected from the child’s health book, where visits on Day 8, Month 9, and 24 are mandatory. Parents complete neurodevelopmental questionnaires at Year 1, Years 2 and 6.
Results:
The RESPONSE study started in August 2019. On 7 April 2023, 515 women were included. Baseline demographics are presented.
Conclusions:
RESPONSE will provide rich information on the global management of pregnancy in France and prospective data on children until the age of 6 years, exposed or not to a DMT, including data on neurodevelopment that can be compared to the general population.
Study funding:
EDMUS and ARSEP Foundation, Biogen, Roche.
Les vaccins ont été soupçonnés de déclencher la sclérose en plaques (SEP) ou les poussées. Avec l’enrichissement des thérapeutiques, des questions se posent sur les risques infectieux ou l’efficacité ...vaccinale.
Etablir des recommandations sur les vaccinations et la SEP. Proposer des documents d’informations aux patients et professionnels de santé sur le calendrier vaccinal adapté aux situations thérapeutiques dans la SEP.
Le Groupe Français pour les Recommandations dans la Sclérose en Plaques (France4MS) a fait une revue systématique des articles issus de PubMed et d’autres bases documentaires publiés entre Janvier 1975 et Juin 2018, selon la méthode de consensus formalisé RAND/UCLA. Vingt-deux experts ont contribué à la rédaction de la revue détaillée et un groupe de 110 professionnels de santé multidisciplinaires a validé la version finale de la synthèse des recommandations.
Les vaccins ne sont pas associés à un risque accru de survenue d’une SEP, y compris les vaccins contre l’hépatite B et le papillomavirus humain ; ils ne sont pas associés à un risque accru de poussée (données insuffisantes pour la fièvre jaune). Il est recommandé de vérifier le statut vaccinal dès le diagnostic et avant introduction de traitements immunoactifs ; d’appliquer le calendrier vaccinal ; de toujours proposer la vaccination contre la grippe saisonnière.
En cas d’immunosuppression, il est recommandé d’informer des risques infectieux et d’appliquer les recommandations du Haut Conseil pour la Santé Publique ; d’appliquer à l’entourage immédiat le calendrier vaccinal, la vaccination contre la grippe et la varicelle ; les vaccins vivants atténués sont contre-indiqués ; les autres vaccins peuvent être proposés, mais leur efficacité pourrait être réduite selon le traitement.
Les professionnels de santé et les patients devraient être informés des recommandations mises à jour sur les vaccinations et la SEP. Ces recommandations pratiques seront diffusées par la SFSEP.
Les infections virales, bactériennes ou fongiques sont soupçonnées de déclencher la sclérose en plaques (SEP) et de favoriser les poussées de la maladie et sont susceptibles d’être favorisées par les ...traitements immuno-actifs. Des questions se posent donc sur le bilan infectieux et sur le traitement préventif de ces infections à effectuer avant leur initiation.
Établir des recommandations sur les infections et la SEP. Proposer des documents d’informations aux patients et aux professionnels de santé sur le bilan infectieux minimal à réaliser chez un patient SEP et avant l’instauration d’un traitement immuno-actif dans la SEP.
Le Groupe Français pour les Recommandations dans la Sclérose en Plaques (France4MS) a fait une revue systématique des articles issus de PubMed et d’autres bases documentaires publiés entre janvier 1975 et juin 2020, selon la méthode de consensus formalisé RAND/UCLA. Vingt-trois experts ont contribué à la rédaction de la revue détaillée et un groupe de 108 professionnels de santé multidisciplinaires a validé la version finale de 36 recommandations.
Il est recommandé chez les patients SEP d’effectuer une bilan infectieux minimal et de vérifier le statut vaccinal, dès le diagnostic et de le renouveler au cours du suivi et avant d’instaurer un traitement immuno-actif. Un dépistage et un traitement préventif des infections virales (groupe Herpes virus, HPV, JCV, HCV, HBV), bactériennes (Mycobactéries) et fongiques (cryptocoque) est recommandé avant l’instauration de certains traitements immuno-actifs de la SEP.
Au moment du diagnostic de SEP et en amont du choix de la stratégie thérapeutique, il est recommandé de procéder à une mise à jour du calendrier vaccinal des patients SEP en référence au calendrier vaccinal du HCSP et aux recommandations de la SFSEP. Avant l’instauration d’un traitement immunosuppresseur il est recommandé d’informer des risques infectieux et de rechercher un déficit immunitaire constitutif ou acquis. Les professionnels de santé et les patients devraient être informés des recommandations mises à jour sur les infections et la SEP.
Background:
Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study.
Objective:
To confirm the efficacy and safety of ...MD1003 in progressive MS in a double-blind, placebo-controlled study.
Methods:
Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5–7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6–7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits.
Results:
A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo.
Conclusion:
MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated.
Even prior to the introduction of criteria defining the radiologically isolated syndrome (RIS), longitudinal clinical data from individuals with incidentally identified T2 lesions suggestive of ...multiple sclerosis (MS) were described. Healthy individuals who do not exhibit signs of neurological dysfunction may have a brain MRI performed for a reason other than suspicion of MS that reveals unexpected anomalies highly suggestive of demyelinating plaques given their size, location, and morphology. These healthy subjects lack a history or symptomatology suggestive of MS and fulfill formal criteria for RIS, a recently described MS subtype that shares the phenotype of at-risk individuals for future demyelinating events. European or North American observational studies have found that up to 30–45% of patients presenting with RIS will present with neurological symptoms, either acute or progressive. The median time to clinical conversion differs between studies. The presence of asymptomatic lesions in the cervical cord indicated an increased risk of progression, either to relapsing or to progressive MS. The consortium studying the epidemiology of RIS worldwide (RISC) presented their first retrospective cohort last year. The mean age at RIS diagnosis was 37.2 years with a mean clinical follow-up time of 4.4 years. The observed 5-year conversion rate to the first clinical event was 34%. Of the converters within this time period, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age, sex (male), and lesions within the cervical or thoracic spinal cord were identified as significant predictors for the development of a first clinical event. Despite progress into the characterization of RIS subjects and into our understanding of risk factors for initial symptom development, the natural course of such cases and risk-profiles for a seminal neurological event, from prospectively acquired data, remain unclear. A prospective study is mandatory to increase our knowledge about these asymptomatic patients and individual therapeutic initiatives cannot be given until a prospective clinical study demonstrates benefit of introducing a disease modifying treatment for this very early stage of a chronic demyelinating disease. Two therapeutic phase III trials using oral disease modifying therapies are on going in Europe and in US.
INTRODUCTIONRituximab (RTX) has been proven effective in managing refractory generalized myasthenia gravis (MG), and its use is increasing worldwide. MG stabilization may initially require oral ...corticosteroid (CS) therapy, but its long-term side effects require the shortest duration of treatment. We studied the clinical effectiveness and usefulness of corticosteroids associated with RTX compared to RTX alone on MG remission.METHODSIn a monocentric retrospective cohort in the Nice University Hospital, we compared naïve MG patients treated with RTX as first-line therapy alone (G1) or associated with CS (G2). After the RTX induction, we evaluated efficacy with the Osserman score (OS) and the requirement for any rescue therapy (IVIg or plasmapheresis).RESULTSSixty-eight patients were treated with RTX, of which 19 (27.94%) benefited from an association with at least 0.5 mg/kg of corticosteroids. RTX-CS patients were more severe than RTX alone (OS for G1: 74.1 and G2: 64.94, p = 0.044). However, OS at 3 (83.44 and 83.12, p = 0.993), 6 (88.69 and 86.36, p = 0.545), 9 (82.91 and 85.73, p = 0.563), and 12 months (86.6 and 88.69, p = 0.761) from the treatment induction were similar. Rescue therapy following RTX induction was significantly higher for the RTX-CS (20.41% and 47.37%, p = 0.037). Regarding safety, adverse event rates were similar in the two groups (0% and 14.29%, p = 0.178).CONCLUSIONWe suggest that RTX alone is as effective as RTX-CS in MG patients, indicating that avoiding steroids could reduce side effects, decrease rescue therapies, and not affect MG outcomes.
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