DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Infarctus cérébral associé à une fibrillation atriale (nouvelles approches diagnostiques)

La documentation de la fibrillation atriale (FA) paroxystique est difficile. Les objectifs de l étude sont de déterminer la prévalence de la FA associée à un infarctus cérébral (IC) ainsi que les modalités diagnostiques optimales de la FA et d évaluer la pertinence des facteurs ou scores prédictifs de la FA retardée. Les patients naïfs de FA admis dans l Unité Neuro-Vasculaire de Nice en phase aigüe d un IC ont bénéficié d un Holter ECG continu durant toute l hospitalisation. La prévalence de la FA a été comparée à différentes modalités d utilisation variant en durée et timing. La pertinence diagnostique des facteurs ou scores prédictifs de la FA occulte a été déterminée par la méthode de comparaison des courbes ROC. 300 patients ont bénéficiés d un Holter prolongé (âge:62,5+-15,5 ans; sexe ratio:1,4 ; NIHSS initial:7,0+-7,9). 17,3% patients ont été nouvellement diagnostiqués en FA. La relation entre durée de l enregistrement ECG continu et rentabilité diagnostique n est pas linéaire. 91% des nouveaux diagnostics sont obtenus dans les 4 premiers jours. Le timing de mise en place du Holter est optimal à l admission comparé à un timing aléatoire (p131 pg/ml), les propriétés diagnostiques du BNP plasmatique sont : sensibilité 98,1%IC95%[89,7-99,7], spécificité 71,3%IC95%[65,3-76,9], valeur prédictive négative 99,4%IC95%[96,9-99,9]. Le Holter ECG continu, précoce et prolongé permet d augmenter le taux de détection de la FA occulte. Il doit être débuté immédiatement à l admission et prolongé au-moins 4 jours. L excellente valeur prédictive du BNP plasmatique pourrait permettre d exclure la FA retardée après un IC dès l admission du patient. Un BNP <= 131 pg/ml permettrait d exclure une FA occulte après un IC. Pour les autres patients, un Holter ECG précoce et prolongé d au-moins 4 jours devrait être proposé.NICE-BU Médecine Odontologie (060882102) / SudocSudocFranceF

Only Follow-up of Memory B Cells Helps Monitor Rituximab Administration to Patients with NeuroMyelitis Optica Spectrum Disorders

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40120-018-0101-4">https://link.springer.com/article/10.1007/s40120-018-0101-4</a></p><p></p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study

BACKGROUND: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating rare disease, often accompanied by high treatment burden and with an unmet need for more efficacious and well tolerated treatments. Zilucoplan is a subcutaneous, self-administered macrocyclic peptide complement C5 inhibitor. We aimed to assess safety, efficacy, and tolerability of zilucoplan in patients with acetylcholine receptor autoantibody (AChR)-positive generalised myasthenia gravis. METHODS: RAISE was a randomised, double-blind, placebo-controlled, phase 3 trial that was done at 75 sites in Europe, Japan, and North America. We enrolled patients (aged 18-74 years) with AChR-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America disease class II-IV), a myasthenia gravis activities of daily living (MG-ADL) score of least 6, and a quantitative myasthenia gravis score of at least 12. Participants were randomly assigned (1:1) to receive subcutaneous zilucoplan 0·3 mg/kg once daily by self-injection, or matched placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in MG-ADL score in the modified intention-to-treat population (all randomly assigned patients who received at least one dose of study drug and had at least one post-dosing MG-ADL score). Safety was mainly assessed by the incidence of treatment-emergent adverse events (TEAEs) in all patients who had received at least one dose of zilucoplan or placebo. This trial is registered at ClinicalTrials.gov, NCT04115293. An open-label extension study is ongoing (NCT04225871). FINDINGS: Between Sept 17, 2019, and Sept 10, 2021, 239 patients were screened for the study, of whom 174 (73%) were eligible. 86 (49%) patients were randomly assigned to zilucoplan 0·3 mg/kg and 88 (51%) were assigned to placebo. Patients assigned to zilucoplan showed a greater reduction in MG-ADL score from baseline to week 12, compared with those assigned to placebo (least squares mean change -4·39 [95% CI -5·28 to -3·50] vs -2·30 [-3·17 to -1·43]; least squares mean difference -2·09 [-3·24 to -0·95]; p=0·0004). TEAEs occurred in 66 (77%) patients in the zilucoplan group and in 62 (70%) patients in the placebo group. The most common TEAE was injection-site bruising (n=14 [16%] in the zilucoplan group and n=8 [9%] in the placebo group). Incidences of serious TEAEs and serious infections were similar in both groups. One patient died in each group; neither death (COVID-19 [zilucoplan] and cerebral haemorrhage [placebo]) was considered related to the study drug. INTERPRETATION: Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study. FUNDING: UCB Pharma

The radiologically isolated syndrome: revised diagnostic criteria

International audienceThe radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the central nervous system within individuals lacking symptoms typical of multiple sclerosis. The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfill 3-4 of 4 criteria for 2005 dissemination in space [DIS] and subjects fulfilling only 1 or 2 lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. 747 subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled 1 or 2 2017 DIS criteria (designated as Group 1 and Group 2, respectively), and 496 (66.4%) fulfilled 3 or 4 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS Group and were more likely to develop new T2 lesions over time (p < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to multiple sclerosis. At five years, the cumulative probability for a clinical event was 29.0% for Groups 1-2 compared to 38.7% for 2009-RIS (p = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at five years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (p < 0.001). The 2009-RIS subjects or Group 1-2 with at least 2 of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria