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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. Three time-to-event outcomes were investigated using flexible parametric survival regression models: time from MS onset to first DMT (any) and to platform therapy, and time from platform therapy to switch to high-efficacy therapy., Results: Overall, 7563 patients were included (mean follow-up 12.6 ± 5.9 years). The percentages of patients aged less than 40 years at MS onset and who initiated treatment before the age of 40 years were significantly higher in the groups with a higher education level. The time-to-event outcomes showed no major difference in DMT practices according to education level, except for women who had a significantly shorter time to DMT initiation in medium to very high education level groups versus low, at 5 years from MS clinical onset., Conclusion: Our results suggest that the association between education level and MS disability progression does not solely reflect different therapeutic practices, particularly in men., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.L., O.D., M.D., C.L.F., and J.P. have nothing to disclose. E.B. disclosed honoraria and consulting fees from Novartis, Sanofi Aventis, Biogen, Genzyme, Roche, and Teva Pharma. J.P.C. disclosed consulting and lecturing fees from Akcea, Alexion, Alnylam, Argenx, Biogen, Bristol Myers Squibb (BMS), CSL Behring, Genzyme, Grifols, Laboratoire Français des Biotechnologies, Merck Serono, Natus, Novartis, Pfizer, Pharmalliance, UCB Pharma, Teva, SNF Floerger; travel grants from Akcea, Alexion, Alnylam, Argenx, Biogen, CSL Behring, Genzyme, Grifols, Laboratoire Français des Biotechnologies, Merck Serono, Natus, Novartis, Pfizer, Teva, SNF Floerger. J.C. disclosed consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi Genzyme, Roche, Celgene BMS, Alexion. P.C. disclosed consulting and lecturing fees, travel grants, and unconditional research support from Biogen, Janssen, MedDay, Merck, Novartis, Roche, Sanofi Genzyme, and Teva Pharma. J.D.S. disclosed consulting and lecturing fees, travel grants, and unconditional research support from Biogen, Genzyme, Novartis, Roche, Sanofi Aventis, and Teva Pharma. O.H. disclosed consulting and lecturing fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall, and Biogen Idec, travel grants from Novartis, Teva, Genzyme, Merck Serono, and Biogen Idec, and research support from Roche, Merck, and Novartis. P.L. disclosed consulting and lecturing fees, travel grants and unconditional research support from Biogen, Genzyme, Novartis, Merck Serono, Roche, and Teva Pharma. D.A.L. served on scientific advisory boards for Alexion, BMS, Roche, Sanofi, Novartis, Merck, Janssen and Biogen, received conference travel support and speaker honoraria from Alexion, Novartis, Biogen, Roche, Sanofi, BMS, Teva Pharma and Merck, and received research support from Fondation ARSEP, Fondation EDMUS and Agence Nationale de la Recherche. L.M. disclosed honoraria as speaker from Biogen, Merck Serono, BMS Celgene, Sanofi Genzyme, Roche, and Novartis. T.M. disclosed fees as scientific adviser from Biogen, MedDay, Novartis, Genzyme, Sanofi. A.R. disclosed consultancy fees, speaker fees, research grants (non-personal), and honoraria approved by the institutions from Novartis, Biogen Idec, Genzyme, Roche, and Merck. E.T. disclosed consulting and lecturing fees, travel grants, or unconditional research support from Actelion, Biogen, Celgene, Genzyme, Merck Serono, Novartis, Roche, Teva Pharma; has a patent pending for biomarkers of neurodegeneration and neuroregeneration and a patent pending for a diagnosis method of MS (EP18305630.8); and received academic research support from PHRC and ARSEP Foundation. S.V. disclosed lecturing fees, travel grants, and research support from Biogen, BMS Celgene, Janssen, Merck, Novartis, Roche, Sanofi Genzyme, Teva. H.Z. disclosed consulting or lectures, and invitations for national and international congresses from Biogen, Merck, Teva, Sanofi Genzyme, Novartis and Bayer, and research support from Teva and Roche, and academic research grants from Académie de Médecine, LFSEP, FHU Imminent, and ARSEP Foundation. G.D. disclosed Consulting and lecturing fees for Biogen, Novartis, Genzyme, Merck Serono, Roche, and Teva and funding for travel from Merck Serono, Biogen, Sanofi Genzyme, Novartis, and Teva. Institution granted for research support from Merck Serono, Biogen, Genzyme, and Novartis. E.L. disclosed consulting and lecture fees or travel grants from Biogen, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Sanofi Aventis, and Roche.

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. Education level was classified into four categories from low (primary/secondary school) to very high (master/doctoral degree). Time from MS onset to EDSS 4.0 was studied using flexible parametric survival models adjusted for age, period, and center, and stratified by phenotype (relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS)) and sex., Results: A total of 11,586 patients were included (women/men ratio = 2.5; age = 36.7 ± 8.6 years; follow-up duration 16.7 ± 9.3 years; 86.4% RMS). For women with RMS, the risk of reaching the outcome at 5 years was inversely associated with the education level (Hazard Ratio medium: 0.74 (0.63-0.87), high: 0.51 (0.43-0.62), very high: 0.39 (0.30-0.50) vs low). Results were similar for men. In PPMS, the risk was significantly different between the extreme groups (very high vs low) for women (0.45 (0.28-0.75)) and men (0.54 (0.32-0.91)), but no gradient was evident., Conclusion: Our study showed a strong association between education level and disability progression, regardless of sex and phenotype., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.L., O.D., M.D., C.L.-F., and J.P. had nothing to disclose. E.B. disclosed honoraria and consulting fees from Novartis, Sanofi Aventis, Biogen, Genzyme, Roche, and Teva Pharma. J.-P.C. disclosed consulting and lecturing fees from Akcea, Alexion, Alnylam, Argenx, Biogen, Bristol Myers Squibb, CSL-Behring, Genzyme, Grifols, Laboratoire Français des Biotechnologies, Merck Serono, Natus, Novartis, Pfizer, Pharmalliance, UCB Pharma, Teva, and SNF-Floerger; travel grants from Akcea, Alexion, Alnylam, Argenx, Biogen, CSL-Behring, Genzyme, Grifols, Laboratoire Français des Biotechnologies, Merck Serono, Natus, Novartis, Pfizer, Teva, and SNF-Floerger. J.C. disclosed consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi-Genzyme, Roche, Celgene-BMS, and Alexion. P.C. disclosed consulting and lecturing fees, travel grants, and unconditional research support from Biogen, Janssen, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva Pharma. J.D.S. disclosed consulting and lecturing fees, travel grants, and unconditional research support from Biogen, Genzyme, Novartis, Roche, Sanofi Aventis, and Teva Pharma. O.H. disclosed consulting and lecturing fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall, and BiogenIdec; travel grants from Novartis, Teva, Genzyme, Merck Serono, and Biogen Idec; and research support from Roche, Merck and Novartis. P.L. disclosed consulting and lecturing fees, travel grants, and unconditional research support from Biogen, Genzyme, Novartis, Merck Serono, Roche, and Teva Pharma. D.A.L. disclosed served on scientific advisory boards for Alexion, BMS, Roche, Sanofi, Novartis, Merck, Janssen, and Biogen; received conference travel support and/or speaker honoraria from Alexion, Novartis, Biogen, Roche, Sanofi, BMS, Teva Pharma, and Merck; and received research support from Fondation ARSEP, Fondation EDMUS, and Agence Nationale de la Recherche. E.L.P. disclosed consulting or lectures, and invitations for national and international congresses from Biogen, Merck, Teva, Sanofi-Genzyme, and Novartis Alexion; research support from Teva and Biogen academic research grants from PHRC and LFSEP; and travel grant from ARSEP Foundation. T.M. disclosed fees as scientific adviser from Biogen, MedDay, Novartis, Genzyme, and Sanofi. A.R. disclosed consultancy fees, speaker fees, research grants (non-personal), and/or honoraria approved by the institutions from Novartis, Biogen Idec, Genzyme, Roche, and Merck. E.T. disclosed consulting and lecturing fees, travel grants, or unconditional research support from the following pharmaceutical companies: Actelion, Biogen, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva Pharma; has a patent pending for biomarkers of neurodegeneration and neuroregeneration and a patent pending for a diagnosis method of multiple sclerosis (EP18305630.8); and received academic research support from PHRC and ARSEP Foundation. S.V. disclosed lecturing fees, travel grants, and research support from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. H.Z. disclosed consulting or lectures and invitations for national and international congresses from Biogen, Merck, Teva, Sanofi-Genzyme, Novartis, and Bayer, as well as research support from Teva and Roche, and academic research grants from Académie de Médecine, LFSEP, FHU Imminent, and ARSEP Foundation. G.D. disclosed Consulting and lecturing fees for Biogen, Novartis, Genzyme, Merck Serono, Roche, and Teva and funding for travel from Merck Serono, Biogen, Sanofi-Genzyme, Novartis, and Teva. Institution granted for research supporting from Merck Serono, Biogen, Genzyme, and Novartis. E.L. disclosed consulting and lecture fees or travel grants from Biogen, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Sanofi Aventis, and Roche.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.J. reports no disclosure. E.J. reports no disclosure. P.L. reports no disclosure. E.M. has received research support from Fondation ARSEP and Biogen Idec, travel funding and/or consulting fees from Alexion, Biogen Idec, BMS, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. J.D.S. reports no disclosure. H.Z. has no disclosure related to this manuscript. Unrelated to this manuscript H.Z. received consulting fees from Biogen Idec, Sanofi, Merck, Novartis, Roche, Horizon Therpaeutics, Alexion, BMS, and Grant Research Support from ROCHE. J.P. reports no disclosure. P.K. reports no disclosure. D.B. reports no disclosure. O.H. has received consulting and lecture fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall, and Biogen Idec, travel grants from Novartis, Teva, Genzyme, Merck Serono, and Biogen Idec, and research support from Roche, Merck, and Novartis. L.G. has received consulting and/or lecture fees and/or travel funding from Novartis, Merck, Sanofi, BMS, and Biogen. C.B. has received consulting honoraria from Alexion, Sanofi, Merck, Biogen, BMS, Novartis, Roche, and Teva. M.T. reports receiving consulting and lecture fees from Merck, Novartis, and Biogen Idec, travel grants from Sanofi, Merck Serono, and Biogen Idec. S.V. has received lecturing fees, travel grants, and research support from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. O.C. reports receiving personal fees from Biogen, Roche, Merck, Novartis, Janssen, and Sanofi and nonfinancial support from Roche, Merck, and Novartis outside the submitted work. A.M. reports no disclosure. D.L. reports receiving grants from Roche, Sanofi, the ARSEP Foundation, the EDMUS Foundation, and the National Agency of Research and receiving personal fees from Biogen, Novartis, Alexion, Merck, and MSD outside the submitted work. E.B. has received honoraria and consulting fees from Alexion, Novartis, Sanofi Aventis, Biogen Idec, Genzyme, Merck, Roche, and Teva. C.L-F. reports no disclosure. B.B. serves on scientific advisory board, has received funding for travel and honoraria from Alexion, Biogen, BMS, Janssen, Merck, Novartis, Sanofi, Roche, and Teva. P.B. reports receiving personal fees from Novartis, Biogen, Merck, BMS, Alexion, and Sanofi outside the submitted work. B.S. reports research support from Roche, Sanofi, and Merck and personal fees for lectures or advisory boards from Novartis, Sanofi, Biogen, Janssen, and Merck. P.C. reports receiving personal fees for board participation from Janssen and Novartis and for board participation and travel from Sanofi and Merck outside the submitted work. E.T. reports receiving personal fees from Biogen, BMS, Janssen, Horizon, Merck, Novartis, and Sanofi outside the submitted work. E.M. reports no disclosure. T.M. reports receiving travel grants and fees for advisory boards from Biogen, Roche, Novartis, Sanofi, and Teva outside the submitted work. F.S. reports receiving consulting and/or lecture fees and/or travel funding from Novartis-Pharma, Biogen, Roche, Sanofi, Linde, and LVL. M.Z. reports receiving expert testimony from Alexion and Novartis, and travel grants from Merck, Roche, and Sanofi Aventis France. C.P. reports receiving honoraria and consulting fees from Alexion, Biogen, Merck, Horizon, and Roche outside the submitted work and serving as president of the Francophone Multiple Sclerosis Society from 2021 to 2024. C.L. has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, and research grant from Biogen.

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.

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: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups., Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation., Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants., Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5)., Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

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.

Background: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses., Objective: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy., Methods: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992-1995 and 2005-2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis., Results: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78)., Conclusion: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

In clinically isolated syndrome (CIS), the detection of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is critical for space dissemination validation when magnetic resonance imaging (MRI) diagnostic criteria are not fulfilled. However, lumbar puncture for CSF collection is considered relatively invasive. Previous studies have demonstrated applicability of OCB detection in tears to the diagnosis of multiple sclerosis (MS). The objective of the present study was to assess concordance between OCB detection in tears and in CSF. We have prospectively included patients with CIS and compared results of CSF and tear OCB detection by isoelectric focusing (IEF). Tears were collected using a Schirmer strip. We included 82 patients. For 69 of them, samples were analysable. OCBs were detected in CSF for 63.8% and in tears for 42% of patients. All patients with tear OCBs had CSF OCBs. We suggest that tear OCB detection may replace CSF OCB detection as a diagnostic tool in patients with CIS. This would circumvent the practice of invasive lumbar punctures currently used in MS diagnosis.