Objectives:
We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin ...oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis.
Material and Methods:
We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0.
Results:
Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p = 0.007 and p = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0–4.0)) compared to SM patients (2.0, (1.0–3.0)), p = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01–1.95, p = 0.046).
Conclusion:
SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.
Background:
Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021.
Objectives:
We ...aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022.
Methods:
This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity.
Results:
Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave (p < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.25–1.64 per 10 years), male sex (OR = 2.01, 95% CI = 1.51–2.67), obesity (OR = 2.36, 95% CI = 1.52–3.68), cardiac comorbidities (OR = 2.36, 95% CI = 1.46–3.83), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = 1.43–3.06 for EDSS 3–5.5 and OR = 4.53, 95% CI = 3.04–6.75 for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = 1.85–3.87) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = 0.60–0.69) or off (RR = 0.32, 95% CI = 0.30–0.33) anti-CD20.
Discussion:
In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status.
Background:
In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression.
Objective:
We aimed to develop and validate a dynamic ...score to guide the early decision to switch from first- to second-line therapy.
Methods:
Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs).
Results:
From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09–0.22) for the waiting group and 0.40 (95% CI 0.32–0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30–0.46) and 0.44 (95% CI 0.37–0.52), respectively.
Conclusions:
By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.
Malgré le nombre important de traitements antiépileptiques, un tiers des patients ne sont pas libre de crise. Le pérampanel est un anti-épileptique récent prometteur de par son nouveau mécanisme ...d’action.
L’objectif de notre étude était d’évaluer l’efficacité et la tolérance du pérampanel chez des patients épileptiques pharmacorésistants et plus particulièrement chez ceux ayant un retard mental et/ou une comorbidité psychiatrique.
Nous avons étudié de manière rétrospective les patients qui ont débuté le pérampanel entre le 1er mai 2014 et le 3 juin 2015. Nous avons recueilli en août 2017 les caractéristiques démographiques et cliniques des patients, de leur épilepsie, ainsi que l’efficacité, la tolérance et la poursuite du traitement pour tous les patients. Puis, nous les avons comparé entre les groupes avec et sans retard mental et/ou comorbidité psychiatrique.
Cent un patients ont été inclus : l’âge moyen était de 41.2 ans, 37.6 % avaient un retard mental et 49.5 % un trouble psychiatrique. Après un suivi de plus de 2 ans, 46.5 % des patients prenaient toujours du pérampanel, 40.6 % étaient répondeurs (diminution de plus de 50 % des crises), dont 5.9 % étaient libres de crise. Il n’y avait pas de différence significative entre les groupes en termes d’efficacité, de tolérance et de taux de rétention du traitement.
Peu d’études de vie courante ont évalué l’efficacité et la tolérance du pérampanel chez des patients ayant une épilepsie pharmacorésitante sévère, avec un suivi aussi long. L’efficacité du traitement semble se poursuivre à long terme, même chez les patients ayant un retard mental ou un trouble psychiatrique.
Le pérampanel semble être un traitement efficace puisque plus d’un tiers des patients reste répondeur même après 2 ans de suivi et près de la moitié des patients le poursuivent.
Abstract Purpose The purpose of this study was to evaluate the effectiveness and safety of PER as add-on treatment in patients with severe refractory epilepsy with a particular focus on patients with ...learning disability and/or psychiatric comorbidity. Method We pooled retrospective data from adult patients with refractory epilepsy prescribed perampanel from a tertiary center in France between 1st May 2014 and 3rd June 2015. Data collection was done on February 2016. Results One hundred and one patients were included (mean age: 41.2 years, 37.6% with learning disability and 49.5% with psychiatric comorbidity). Mean retention was 8.1 months (range: 14 days to 17 months). On final evaluation, a > 50% reduction in seizure frequency was reached in 41.6% of patients, and 7 patients (6.9%) became seizure-free. Sixty-three patients (62.4%) experienced adverse effects. The most common adverse effects were irritability, asthenia, aggression, and sedation. Efficacy, retention of treatment, and safety were equally similar in patients with learning disability or psychiatric comorbidity as for those without. The only significant difference was in percentage of seizure-free patients: 11.1% in the group without learning disability compared with 0% in the group with (p = 0.043). Conclusion Adjunctive PER can achieve clinically meaningful improvement, or even seizure freedom, in more than one-third of patients suffering from severe refractory epilepsies. It seems similarly safe and effective in the subgroup of these patients with learning disability or with psychiatric comorbidity. However, the rate of psychiatric side effects is high,; of note, we asked both patient and caregivers at each visit especially focusing on psychiatric side effects. Patients, caregivers, and families should be informed of potential psychiatric/behavioral risks associated with taking perampanel especially during the initial titration period.
Summary
Objective
To pool observational data on the routine use of perampanel to obtain information on real‐world outcomes and data in populations typically underrepresented in clinical trials.
...Methods
Individual‐level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1‐year retention rate, 1‐year seizure freedom rate (duration ≥6 months), and incidence of treatment‐emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses.
Results
The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One‐year retention rate was 48% (1117/2332; 95% confidence interval CI 46‐50%), and 1‐year seizure‐free rate (≥6‐month duration) was 9.2% (74/803; 95% CI 7‐11%). Median treatment duration was 11.3 months (1832 patient‐years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66‐70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure‐free rate, and higher number of prior AEDs with lower seizure‐free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1‐year retention rate was 48% and seizure‐free rate was 28%.
Significance
Across a large, treatment‐resistant population, add‐on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure‐free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel.
Summary Objectives The objective of the present study was to evaluate the prevalence of obstructive sleep apnea (OSA) in patients with late-onset epilepsy (LOE) who were considered at higher risk of ...cardiovascular disease. Methods Polysomnography was performed on 27 patients with LOE. Berlin questionnaires and Epworth sleepiness score were performed on all patients. We compared clinical, demographic and anthropometric characteristics, questionnaire scores on the patients with no or mild OSA (group 1) and the patients with moderate or severe OSA (group 2). Patients eligible for continuous positive airway pressure (CPAP) therapy were reviewed in consultation. Results Twenty-four patients (88.9%) had OSA and 55.6% had moderate or severe OSA. Patients in group 2 ( n = 15) were older than patients in group 1 ( n = 12). The two groups were similar in terms of body mass index (BMI), neck circumference, nocturnal seizure frequency, vascular cardiovascular risk factors and excessive daytime sleepiness. Leukoaraiosis in MRI was highly prevalent in our patients (40.7%), especially in group 2 patients. Eighty percent of the patients who had begun CPAP therapy experienced decreased seizure frequency. Conclusion Patients with LOE should be screened for the presence of OSA and treated accordingly.
A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of ...data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity.
To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET.
This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques OFSEP database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022.
Natalizumab, fingolimod, rituximab, and ocrelizumab.
Time to first relapse.
Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean SD age, 57.7 5.5 years; mean SD delay since the last inflammatory activity, 5.6 3.8 years; mean SD follow-up duration after propensity score matching, 2.5 2.1 years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy.
As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.
The question of the long-term safety of pregnancy is a major concern in patients with multiple sclerosis (MS), but its study is biased by reverse causation (women with higher disability are less ...likely to experience pregnancy). Using a causal inference approach, we aimed to estimate the unbiased long-term effects of pregnancy on disability and relapse risk in patients with MS and secondarily the short-term effects (during the perpartum and postpartum years) and delayed effects (occurring beyond 1 year after delivery).
We conducted an observational cohort study with data from patients with MS followed in the Observatoire Français de la Sclérose en Plaques registry between 1990 and 2020. We included female patients with MS aged 18-45 years at MS onset, clinically followed up for more than 2 years, and with ≥3 Expanded Disease Status Scale (EDSS) measurements. Outcomes were the mean EDSS score at the end of follow-up and the annual probability of relapse during follow-up. Counterfactual outcomes were predicted using the longitudinal targeted maximum likelihood estimator in the entire study population. The patients exposed to at least 1 pregnancy during their follow-up were compared with the counterfactual situation in which, contrary to what was observed, they would not have been exposed to any pregnancy. Short-term and delayed effects were analyzed from the first pregnancy of early-exposed patients (who experienced it during their first 3 years of follow-up).
We included 9,100 patients, with a median follow-up duration of 7.8 years, of whom 2,125 (23.4%) patients were exposed to at least 1 pregnancy. Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference 95% CI = 0.00 -0.16 to 0.15) or on the annual probability of relapse (causal risk ratio 95% CI = 0.95 0.93-1.38). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate.
Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias.
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