Publications by authors named "Gilles Defer"
Background: We hypothesized that differences in access to disease-modifying treatments (DMTs) could explain the association between socioeconomic status and disability progression in multiple sclerosis (MS).
Objective: This study aimed to analyze the association between education level and DMT use in France.
Methods: All patients from OFSEP network with MS onset over 1996-2014 and aged ⩾ 25 years at onset were included.
Background: Studies have reported an association between socioeconomic status and disability progression in multiple sclerosis (MS), but findings using the pre-MS individual socioeconomic status are missing.
Objective: The objective was to investigate the association between education level and disability progression.
Methods: All Observatoire Français de la Sclérose en Plaques (OFSEP) patients with MS clinical onset over 1960-2014, and aged ⩾25 years at MS onset were included.
Article Synopsis
- * Results from the NOVA clinical trial show that while patients on Q6W dosing had lower levels of natalizumab compared to Q4W dosing, they still maintained significant clinical efficacy with most patients experiencing stable disease markers over 72 weeks.
- * Key findings included a 23.6% increase in soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in the Q6W
Article Synopsis
- The study aimed to compare disability progression between primary progressive multiple sclerosis (PPMS) patients treated with anti-CD20 therapies (rituximab and ocrelizumab) and a control group that was untreated.
- Data was gathered retrospectively from the French MS registry, including factors like time to confirmed disability progression (CDP), relapse rates, and MRI activity in patients from 2016 to 2021.
- Results showed no significant difference in CDP or MRI activity between treated and untreated groups, although a trend suggested treated patients might experience fewer relapses, warranting further investigation.
Introduction: Following NOVA (part 1) and the approval of the subcutaneous (SC) route of administration of natalizumab by the European Medicines Agency, an extension phase of the NOVA phase IIIb study (part 2) was initiated to collect patient preference data for SC versus intravenous (IV) dosing in patients receiving every-6-week (Q6W) dosing of natalizumab. This study was performed to evaluate patient preference for SC versus IV natalizumab administration and explore the efficacy, safety, and pharmacology characteristics of both routes of administration.
Methods: In part 2, participants received natalizumab (Tysabri) 300 mg via IV infusion Q6W for 36 weeks and then were randomized to 48 weeks of crossover treatment (24 weeks SC Q6W and 24 weeks IV Q6W, or vice versa).
Article Synopsis
- * Conducted over eight years (2015-2023) using data from a French MS registry, researchers categorized relapses based on MRI results to better understand their impact.
- * Findings indicate that certain factors, like treatment type and fatigue, increase the likelihood of clinically defined relapses without MRI evidence, suggesting a need for revised monitoring and treatment strategies for MS patients.
Article Synopsis
- A randomized clinical trial suggests that stopping medium-efficacy therapy for older patients with nonactive multiple sclerosis (MS) may be safe, but data is lacking for high-efficacy therapy (HET).
- This observational cohort study from the French MS registry examined 1857 older patients with relapsing-remitting MS on HET and aimed to find out if stopping HET increased relapse risks.
- The study included 1620 matched patients, with results indicating that both groups (continuing vs. discontinuing HET) were closely monitored over an average of 5.1 years to determine the time to first relapse.
Background: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk.
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- Moderately effective therapies (METs) have been the standard treatment for pediatric-onset multiple sclerosis (POMS), but there's still no clear consensus on treatment strategies as highly effective therapies (HETs) emerge.
- The study aimed to evaluate the effectiveness of HET compared to MET in reducing disease activity in treatment-naive children with relapsing-remitting POMS, using a retrospective cohort design over a median follow-up of 5.8 years.
- Results from 530 included patients indicated that both HET and MET reduced the risk of relapse within the first 2 years, with HET showing a significant 54% decrease in first relapses compared to MET.
Article Synopsis
- This study compares two methods for estimating death probabilities in multiple sclerosis (MS) patients: the Cause-Specific Framework (CSF) which requires known causes of death, and the Excess Mortality Framework (EMF) which does not.
- Using data from a large MS registry and a subset with detailed death records, the researchers found that EMF generally estimated higher death probabilities than CSF across different age groups.
- Overall, the analysis revealed varying mortality probabilities for MS patients based on the initial disease type, sex, and age; with significant differences particularly noted between relapsing-onset MS and primary progressive patients over a 30-year follow-up.
Article Synopsis
- * Serious side effects like extreme lymphopenia are rare, but monitoring for infections and screening for liver function are recommended before starting CladT treatment.
- * The risk of developing malignancies with CladT is similar to general population rates and other treatments, and overall, CladT is considered to have a good safety profile for RMS management.
Background: Natalizumab (TYSABRI®) 300 mg administered intravenously every-4-weeks (Q4W) is approved for treatment of relapsing-remitting multiple sclerosis but is associated with increased risk of progressive multifocal leukoencephalopathy (PML). Extended natalizumab dosing intervals of approximately every-6-weeks (Q6W) are associated with a lower risk of PML. Primary and secondary clinical outcomes from the NOVA randomized clinical trial (NCT03689972) suggest that effective disease control is maintained in patients who were stable during treatment with natalizumab Q4W for ≥12 months and who then switched to Q6W dosing.
View Article and Find Full Text PDFIntroduction: 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.
The treatment strategy in relapsing multiple sclerosis (RMS) is a complex decision requiring individualization of treatment sequences to maximize clinical outcomes. Current local and international guidelines do not provide specific recommendation on the use of immune reconstitution therapy (IRT) as alternative to continuous immunosuppression in the management of RMS. The objective of the program was to provide consensus-based expert opinion on the optimal use of IRT in the management of RMS.
View Article and Find Full Text PDFBackground And Objectives: 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).
Methods: 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.
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.
Background: The effects of socio-economic status on mortality in patients with multiple sclerosis is not well known. The objective was to examine mortality due to multiple sclerosis according to socio-economic status.
Methods: A retrospective observational cohort design was used with recruitment from 18 French multiple sclerosis expert centers participating in the All patients lived in metropolitan France and had a definite or probable diagnosis of multiple sclerosis according to either Poser or McDonald criteria with an onset of disease between 1960 and 2015.
Article Synopsis
- The study explores the link between socioeconomic status (SES) and mortality among people with multiple sclerosis (PwMS), highlighting a gap in understanding.
- Researchers analyzed data from 12,126 MS patients diagnosed between 1994 and 2017, using a statistical model to evaluate the impact of SES on mortality risk.
- Findings indicate that lower SES is significantly linked to higher mortality risk, with the most deprived individuals facing a mortality risk 61% higher than those least deprived.
Article Synopsis
- - Transverse myelitis (TM) has been linked to the Janssen/Johnson & Johnson SARS-CoV-2 vaccine, but the relationship with other vaccines like Pfizer, Moderna, AstraZeneca, and Novavax is unclear, prompting this study to explore these associations.
- - The research analyzed safety reports from the WHO's VigiBase, focusing on TM cases occurring within 28 days after receiving any FDA or EMA approved SARS-CoV-2 vaccine between December 2020 and March 2022.
- - Results indicated a significant association between both mRNA-based and vector-based vaccines and TM, yet TM is still rare (0.28 cases per million doses), suggesting the overall benefits of vaccination outweigh the risks
Background: Treatment with natalizumab once every 4 weeks is approved for patients with relapsing-remitting multiple sclerosis, but is associated with a risk of progressive multifocal leukoencephalopathy. Switching to extended-interval dosing is associated with lower progressive multifocal leukoencephalopathy risk, but the efficacy of this approach is unclear. We aimed to assess the safety and efficacy of natalizumab once every 6 weeks compared with once every 4 weeks in patients with relapsing-remitting multiple sclerosis.
View Article and Find Full Text PDFIn France, two therapeutic strategies can be offered after fingolimod (FNG) withdrawal to highly active relapsing-remitting multiple sclerosis (RRMS) patients: natalizumab (NTZ) or anti-CD20. We compared the effectiveness of these two strategies as a switch for FNG within the OFSEP database. The primary endpoint was the time to first relapse.
View Article and Find Full Text PDFBackground: Cognitive deficits are common in multiple sclerosis (MS) and affect patients at all stages of the disease, regardless of phenotype.
Aims: This literature review focuses the cognitive deficits observed in secondary progressive MS (SPMS). It is mainly based on studies that compared the frequency and main characteristics of cognitive deficits in SPMS with other phenotypes.
Article Synopsis
- Natalizumab outperforms fingolimod in reducing relapses in patients with relapsing-remitting multiple sclerosis (RRMS), but it's unclear if this holds true for all demographic groups.
- The study aimed to assess the effectiveness of these treatments across different patient subgroups, considering factors like age, sex, disease duration, and disability status.
- Results showed that natalizumab led to fewer relapses and a higher chance of improving disability in various subgroups, indicating its potential superiority, particularly in younger patients and those with less severe disease.
The risk of cancer associated with persons with multiple sclerosis (pwMS) prescribed with disease modifying therapies (DMTs) is not well established. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database: VigiBase®. All consecutive reports of DMTs prescribed to pwMS (alemtuzumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-β, natalizumab, ocrelizumab, and teriflunomide), and their serious adverse event cases were eligible, excluding those reporting immunosuppressant DMTs used as anticancer therapies.
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