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.
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.
To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD).
We ...retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR).
A total of 136 patients were included: 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio HR, 2.74 1.17-6.40;
= 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 0.72-6.28;
= 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF (
= 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA.
The use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status.
That study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse.
Background:
The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined.
Objective:
The aim of ...this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network.
Methods:
Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference.
Results:
A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower (p < 0.0004) for the first quintile patients’ group.
Conclusion:
Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
Objective
The main objective was to compare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) dynamics between children and adults with MOG‐Ab–associated ...disease (MOGAD).
Methods
This retrospective multicentric, national study included 98 children and 268 adults with MOGAD between January 2014 and September 2019. Cox regression model for recurrent time‐to‐event data and Kaplan–Meier curves for time to antibody negativity were performed for the objectives.
Results
Isolated optic neuritis was the most frequent clinical presentation in both children (40.8%) and adults (55.9%, p = 0.013), and acute disseminated encephalomyelitis syndrome was more frequent in children (36.7% vs 5.6%, p < 0.001). Compared to adults, children displayed better recovery (Expanded Disability Status Scale ≥ 3.0 at last follow‐up reached only by 10 of 97 10.3% vs 66/247 26.7%, p < 0.001). In the multivariate analysis, adults were at higher risk of relapse than children (hazard ratio = 1.41, 95% confidence interval CI = 1.12–1.78, p = 0.003). At 2 years, 64.2% (95% CI = 40.9–86.5) of nonrelapsing children became MOG‐Ab negative compared to 14.1% (95% CI = 4.7–38.3) of relapsing children (log‐rank p < 0.001), with no differences observed in adults (log‐rank p = 0.280).
Interpretation
MOGAD patients differ in the clinical presentation at onset, showing an age‐related shift in the clinical features across age groups. Compared to children, adults have a higher risk of relapse and worse functional recovery. Finally, children with monophasic disease become MOG‐Ab negative earlier than relapsing children, but this is not true in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults. ANN NEUROL 2021;89:30–41
The influence of the patterns of onset of multiple sclerosis and relapses of the disease on the time course of irreversible disability is controversial.
In 1844 patients with multiple sclerosis who ...were followed for a mean (+/- SD) of 11 +/- 10 years, we determined the time of the clinical onset of the disease, the initial course (relapsing-remitting or progressive) and the subsequent course (relapsing-remitting, secondary progressive, or primary progressive), the times of relapses, the time to the onset of irreversible disability, and the time course of progressive, irreversible disability. We used three scores on the Kurtzke Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability) as measures of the severity and progression of disability: a score of 4 (limited walking ability but able to walk for more than 500 m without aid or rest), a score of 6 (ability to walk with unilateral support no more than 100 m without rest), and a score of 7 (ability to walk no more than 10 m without rest while leaning against a wall or holding onto furniture for support). We used Kaplan-Meier analyses to determine the influence of relapses on the time to the onset of irreversible disability.
The median times from the onset of multiple sclerosis to the assignment of a score of 4, a score of 6, and a score of 7 on the disability scale were longer among the 1562 patients with a relapsing-remitting onset of disease (11.4, 23.1, and 33.1 years, respectively) than among the 282 patients who had progressive disease from the onset (0.0, 7.1, and 13.4 years, respectively; P<0.001 for all comparisons). In contrast, the times from the assignment of a score of 4 to a score of 6 were similar in the two groups (5.7 and 5.4 years, P=0.74). The time course of progressive, irreversible disease among patients with the primary progressive type of multiple sclerosis was not affected by the presence or absence of superimposed relapses.
Among patients with multiple sclerosis, relapses do not significantly influence the progression of irreversible disability.
Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in ...adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included. Comprehensive epidemiological, clinical, radiological, and laboratory data were retrospectively analyzed. Additionally, we compared radiological features between ADEM MOG-Ab-positive patients, and a group of ADEM MOG-Ab-negative ones, recruited during the same period. Among the whole cohort, 13 (48.1%) were pediatric, and 14 (51.9%) were female. MOG-Ab-related disorders comprised eight ADEM, eight ON, five isolated myelitis, four with NMOSD and two patients with multiple sclerosis, at last follow-up. After a median follow-up of 17.8 months, 11 (40.7%) patients presented a relapse. The most frequent clinical phenotype at onset was encephalopathy in pediatrics (53.9%) and myelitis in adults (50%) (
p
= 0.013). There were no other differences between both groups. When comparing ADEM MOG-Ab positive and negative patients, bilateral thalamic lesions were more often found in the positive group (
p
= 0.010). Unusual presentations were identified in three patients: patchy spinal cord gadolinium-enhancing lesions, an associated teratoma, and one presented with status epilepticus. MOG-Ab-related disorders shared common clinical and prognostic features, but encompass a spectrum wider than recently reported.
Background
The Big Multiple Sclerosis Data (BMSD) network (
https://bigmsdata.org
) was initiated in 2014 and includes the national multiple sclerosis (MS) registries of the Czech Republic, Denmark, ...France, Italy, and Sweden as well as the international MSBase registry. BMSD has addressed the ethical, legal, technical, and governance-related challenges for data sharing and so far, published three scientific papers on pooled datasets as proof of concept for its collaborative design.
Data collection
Although BMSD registries operate independently on different platforms, similarities in variables, definitions and data structure allow joint analysis of data. Certain coordinated modifications in how the registries collect adverse event data have been implemented after BMSD consensus decisions, showing the ability to develop together.
Data management
Scientific projects can be proposed by external sponsors via the coordinating centre and each registry decides independently on participation, respecting its governance structure. Research datasets are established in a project-to-project fashion and a project-specific data model is developed, based on a unifying core data model. To overcome challenges in data sharing, BMSD has developed procedures for federated data analysis.
Future perspectives
Presently, BMSD is seeking a qualification opinion from the European Medicines Agency (EMA) to conduct post-authorization safety studies (PASS) and aims to pursue a qualification opinion also for post-authorization effectiveness studies (PAES). BMSD aspires to promote the advancement of real-world evidence research in the MS field.
Multiple sclerosis is often diagnosed in patients who are planning on having children. Although multiple sclerosis does not negatively influence most pregnancy outcomes, less is known regarding the ...effects of fetal exposure to novel disease-modifying therapies (DMTs). The withdrawal of some DMTs during pregnancy can modify the natural history of multiple sclerosis, resulting in a substantial risk of pregnancy-related relapse and disability. Drug labels are typically restrictive and favour fetal safety over maternal safety. Emerging data reporting outcomes in neonates exposed to DMTs in utero and through breastfeeding will allow for more careful and individualised treatment decisions. This emerging research is particularly important to guide decision making in women with high disease activity or who are treated with DMTs associated with risk of discontinuation rebound. As increasing data are generated in this field, periodic updates will be required to provide the most up to date guidance on how best to achieve multiple sclerosis stability during pregnancy and post partum, balanced with fetal and newborn safety.
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