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.
Aims
To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable ...immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real‐life setting.
Methods
A population‐based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1–3.5 years of follow‐up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± 95% CI) of ARRt and the odds ratio (OR ± 95% CI) of disability progression, respectively.
Results
Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF‐IMM patients, 1679 DMF‐TERI patients, and 376 DMF‐FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 0.61–0.86) and TERI (0.81 0.68–0.96) and did not show any significant difference when compared with FTY. The risk of the progression of MS‐specific disability was not significantly different for any matched cohorts.
Conclusion
DMF is associated with lower risk of treated relapse for patients with RRMS than other first‐line RRMS agents (TERI and IIM).
The objective of this study is to investigate the efficacy of psychological Interventions - Mindfulness or Implementation Intention - associated with a Physical Activity program, delivered via ...internet, in reducing Multiple Sclerosis symptoms.
Thirty-five adults were randomly assigned to one of the three groups: a Mindfulness-Based Intervention group (
= 12), Implementation Intention group (
= 11), and a Control Group (
= 12). All the groups received the same Physical Activity program. The Mindfulness condition group received daily training in the form of pre-recorded sessions while the Implementation group elaborated their specific plans once a week. Mobility, fatigue, and the impact of the disease on the patient's life were measured. Two measurement times are carried out in pre-post intervention, at baseline and after eight weeks.
Overall, after 8 weeks intervention, results show that there was a significant increase in Walking distance in the three groups. In addition, the within-group analysis showed a statistically significant improvement between pre and post intervention on the physical component of the Disease Impact scale in the Implementation Intention group (
= 0.023) with large effect size, in the Mindfulness-Based Intervention group (
= 0.008) with a medium effect size and in the control group (
= 0.028) with small effect size. In the Implementation Intention group, all physical, psychosocial and cognitive Fatigue Impact subscales scores decreased significantly (
= 0.022,
= 0.023, and
= 0.012, respectively) and the physical component was statistically and negatively correlated (
=
=
) when Implementation Intention group practice a mild to moderate physical activity. In the Mindfulness-Based Intervention group, the physical component (MFIS) showed a statistically significant improvement (
= 0.028) but no correlation with moderate-to-vigorous physical activity (MVPA); the control group outcomes did not reveal any significant change.
The results of this study are very encouraging and show the feasibility of Mindfulness interventions associated with physical activity to improve the health of people with MS. Further study should assess Mindfulness interventions tailored to MS condition and using both hedonic and eudemonic measures of happiness.
Few cases of human papillomavirus (HPV) diseases have been reported in multiple sclerosis (MS) patients treated with fingolimod. We describe a case series of 16 MS patients (11 women, 5 men) ...developing HPV lesions after the onset of fingolimod, without previous HPV history. Fingolimod had to be discontinued in six patients. Six patients received vaccination for HPV, with good tolerance. Our report highlights that systematic HPV screening and discussion about HPV vaccination before fingolimod onset are crucial. In case of occurrence of HPV lesions during fingolimod treatment, a comprehensive workup of HPV disease is necessary, with discussion of HPV vaccination to prevent secondary lesions. Prevalence studies of HPV lesions are needed in MS patients with the different disease-modifying therapies.
Background
Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve ...disability in patients with progressive MS.
Objective
The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss.
Methods
The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye visual acuity (VA) below 0.5 decimal chart were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed.
Results
Ninety-three patients received MD1003 (
n
= 65) or placebo (
n
= 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (
p
= 0.66) with MD1003 (− 0.061 logMAR, + 3.1 letters) than with placebo (− 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (− 0.058 logMAR) with MD1003 and worsened by − 1.5 letters (+ 0.029 logMAR) with placebo (
p
= 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo.
Conclusions
MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated.
Trial registration
EudraCT identifier 2013-002112-27. ClinicalTrials.gov Identifier: NCT02220244
Funding
MedDay Pharmaceuticals.
High-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Several reports have suggested that HDB treatment may be associated with an increased risk of relapse. We ...aimed to determine whether HDB increases the risk of clinical relapse in PMS and describe the characteristics of the patients who experience it. We conducted a French, multicenter, retrospective study, comparing a group of PMS patients treated with HDB to a matched control group. Poisson regression was applied to model the specific statistical distribution of the annualized relapse rate (ARR). A propensity score (PS), based on the inverse probability of treatment weighting (IPTW), was used to adjust for indication bias and included the following variables: gender, primary PMS or not, age, EDSS, time since the last relapse, and co-prescription of a DMT. Two thousand six hundred twenty-eight patients treated with HDB and 654 controls were analyzed with a follow-up of 17 ± 8 months. Among them, 148 validated relapses were observed in the group treated with biotin and 38 in the control group (
p
= 0.62). After adjustment based on the PS, the ARR was 0.044 ± 0.23 for the biotin-treated group and 0.028 ± 0.16 for the control group (
p
= 0.18). The more relapses there were before biotin, the higher the risk of relapse during treatment, independently from the use of HDB. While the number of relapses reported for patients with no previous inflammatory activity receiving biotin has gradually increased, the present retrospective study is adequately powered to exclude an elevated risk of relapse for patients with PMS treated with HDB.
Background:
Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy.
Objective:
To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with ...nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo.
Methods:
POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo.
Results:
Recruitment was stopped prematurely due to slow inclusions (n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58–1.39), placebo = 0.97 (0.63–1.50) (p = 0.79)).
Conclusion:
POPARTMUS failed showing efficacy of a NOMAc–E2 combination in preventing post-partum relapses.
Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, ...intra-database validation can present an appropriate alternative.
To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs).
Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conducted to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each disease, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm.
Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV. Algorithm for mCRPC identification showed a 97% PPV and 99% NPV.
The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative.
L’absence de consommation de produits d’origine animale et de produits laitiers peut entraîner des déficits en acides aminés, vitamine B12, en fer ou en vitamine D. Nous rapportons un cas de ...myélopathie par déficit en vitamine B12, chez une patiente végétalienne.
Le début remonte à 2019 par des troubles de l’équilibre et de la marche. L’examen neurologique a mis en évidence une ataxie à la marche, des dysesthésies au tact jusqu’à mi-cuisse, des réflexes ostéotendineux abolis, des troubles de coordination des deux membres inférieurs. Le reste de l’examen clinique était sans particularité. L’IRM médullaire objectivait un hypersignal T2 postéro-médial bilatéral et symétrique, des faisceaux postérieurs de la moelle spinale cervicale de C2 à C5–C6. L’ENMG montrait une diminution des amplitudes sensitives diffuses sur l’ensemble des nerfs sensitifs. La fibroscopie gastrique, la coloscopie et l’entéro IRM étaient normaux. Le taux sérique de vitamine B12 était diminué : 61pmol/L (N 100–600). Le bilan biologique sanguin révélait une anémie macrocytaire, une hypothyroïdie, une dénutrition et d’autres carences vitaminiques (B9, E et C). L’injection par voie intramusculaire de vitamine B12 à la dose initiale de 1000μg/j permettait une amélioration partielle. Une reprise de la marche sans aide fut possible après le traitement mais avec des séquelles ataxiques. L’imagerie médullaire de contrôle à 24 mois montrait la persistance de l’hypersignal T2 postérieur. La patiente n’a pas interrompu son mode d’alimentation sous couvert d’une supplémentation en vitamine B12.
La cobalamine, peu représentée dans les plantes est une molécule essentielle pour l’homme qui agit comme un cofacteur dans les transferts d’un carbone par méthylation et réarrangement moléculaire. L’adoption croissante de styles alimentaires végétaliens qui excluent les aliments d’origine animale, exposent les consommateurs à des carences potentiellement sévères en Vitamine B12.
Les patients végétaliens doivent être informés des risques de carence vitaminique associé et doivent être systématiquement supplémentés en vitamine B12.
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