L'équipe du CRCSEP était présente au MSMilan2023 de l'ECTRIMS.

Le Professeur Lebrun-Frenay et son équipe ont réalisé ou participé aux présentations suivantes :

Towards a more precise rating of neurological disability in multiple sclerosis: A new automatic and linear quantification of the neurological exam

Mikael Cohen¹, Lydiane MONDOT¹, Cassandre LANDES-CHATEAU¹, Christine Lebrun-Frenay¹

¹UMRC UR2CA URRIS; CRC SEP, CHU de Nice, France, Nice, France

Introduction: The Expanded Disability Status Scale (EDSS) is the gold standard for evaluating clinical disability in multiple sclerosis (MS). However, disease management could benefit from more precise clinical assessment tools for monitoring of disability progression.

Objectives/Aims: This study assessed the correlation between a mobile application (Quantified Neurological Examination – QNE) that provides a fully automated rating of the neurological examination, EDSS and MRI metrics.

Methods: MS patients referred to our centre were assessed for EDSS score and QNE application that automatically provides a global score and subscores (qFSS) based on the EDSS functional system scores (FSS) from the description of the neurological examination. QNE score and qFSS scores are ranging from 0 to 100, which represents a normal examination.

For patients with a recent brain MRI, images were analysed with Volbrain software to obtain automatic measures of global and regional atrophy.

We assessed the correlation between EDSS, FSS, QNE global score, qFSS and MRI metrics.

Results: We performed two hundred examinations and included seventy-eight patients in the MRI analysis.

The global QNE score was strongly correlated with the EDSS (ρ = -0.87, r2 = 0.76, p<0.0001).

qFSS was statistically different according to the corresponding FSS for each function (p<0.01), except for the visual FSS for which the statistical analysis lacked power as the FSS score was rated to 0 in 178/200 (89%) of total examinations.

EDSS was predominantly correlated to the pyramidal function of the lower limbs (ρ = -0.83, r2 = 0.62, p<0.001) compared to upper limbs (ρ = -0.49, r2 = 0.26, p<0.001). In the subgroup of patients with an EDSS higher than 4, EDSS was only correlated to lower limbs function (ρ = -0.4, r2 = 0.2, p = 0.05).

QNE score and qFSS had a stronger correlation to brain MRI measures than EDSS, particularly regarding the grey matter volume (ρ = 0.58, p<0.0001) and cortical volume (ρ = 0.5, p<0.0001).

Conclusion: We propose an automated method to rate neurological disability in MS. While QNE strongly correlates with EDSS, it may allow a more precise way to monitor the evolution of disability without requiring any rating task by the physician.

Disclosure of interest: Mikael Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ad Scientiam, Biogen, Merck, Sanofi-Genzyme, Roche, Celgene-BMS, Alexion, Horizon Therapeutics.

Lydiane Mondot: nothing to disclose

Cassandre Landes-Chateau: nothing to disclose

Christine Lebrun-Frenay: nothing to disclose

Silent Progression Activity Monitoring in MS despite an early highly active treatment: the SPAM study

Mikael Cohen¹, Fabien ROLLOT^2,3,4,5, Marc Debouverie⁶, Helene ZEPHIR⁷, Sandra Vukusic^2,3,4, Jérôme De Seze⁸, Pierre Labauge⁹, Aurelie Ruet¹⁰, Eric BERGER¹¹, David LAPLAUD¹², JONATHAN CIRON^13,14, Bertrand Bourre¹⁵, Emmanuelle Le Page¹⁶, Caroline Papeix¹⁷, Eric Thouvenot¹⁸, Abdullatif Al Khedr¹⁹, Bruno Stankoff²⁰, Jean Pelletier²¹, Elisabeth Maillart²², Olivier Casez²³, Thibault Moreau²⁴, Gilles Defer²⁵, Pierre Clavelou²⁶, Philippe Cabre²⁷, Solène Moulin²⁸, JEAN PHILIPPE NEAU²⁹, ABIR WAHAB³⁰, Karolina Hankiewicz³¹, Inès Doghri³², Haifa Khaled³³, Corinne Pottier³⁴, Laurent Magy³⁵, Dalia Meshaka Dimitri Boulos³⁶, Olivier Heinzlef³⁷, Jean-Philippe Camdessanche³⁸, Marc COUSTANS³⁹, Chantal Nifle⁴⁰, David Brassat⁴¹, Romain Casey^2,3,4,5, Christine Lebrun-Frenay¹

Study Group: OFSEP

¹CRC SEP, UMRC UR2CA URRIS, CHU de Nice, Nice, France, ²Claude Bernard University Lyon 1, Villeurbanne, France, ³Pierre Wertheimer Hospital, Bron, France, ⁴Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, Lyon, France, ⁵EUGENE DEVIC EDMUS Foundation against multiple sclerosis, state-approved foundation, Bron, France, ⁶Hospital Center Regional And University De Nancy Hospital Central, Nancy, France, ⁷Chu De Lille, Lille, France, ⁸Chu Strasbourg, Strasbourg, France, ⁹Hospital Center University De Montpellier, Montpellier, France, ¹⁰Hôpital Pellegrin Bordeaux, Bordeaux, France, ¹¹Besançon Regional University Hospital Center, Besançon, France, ¹²Centre hospitalier universitaire de Nantes, Nantes, France, ¹³Department of Neurology, CRC-SEP, University Hospital of Toulouse, Hôpital Pierre-Paul Riquet, Toulouse, France, ¹⁴Infinity Inserm U1291, Toulouse, France, ¹⁵Hospital Center University De Rouen, Rouen, France, ¹⁶Rennes University, CHU Rennes, CRC-SEP Neurology Department, CIC Inserm 1414, Rennes, France, ¹⁷Hospital Foundation Adolphe De Rothschild, Neurology department, Paris, France, ¹⁸University Hospital of Nimes, Nîmes, France, ¹⁹CHU Amiens-Picardie, Amiens, France, ²⁰Hospital Saint-Antoine Ap-Hp, Paris, France, ²¹Aix Marseille Univ, APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France, ²²University Hospitals Pitié Salpêtrière - Charles Foix, Paris, France, ²³Chu Grenoble Alpes, La Tronche, France, ²⁴Chu Dijon, Dijon, France, ²⁵University Hospital Center of Caen, Caen, France, ²⁶CHU Gabriel-Montpied, Clermont-Ferrand, France, ²⁷CHU de MARTINIQUE - MFME, Fort-de-France, Martinique, ²⁸CHU Reims - Champagne Clinic, Reims, France, ²⁹Poitiers University Hospital, Poitiers, France, ³⁰Henri-Mondor University Hospital, Créteil, France, ³¹Saint-Denis Hospital Center, Saint-Denis, France, ³²Chru Hospitals Of Tours, Tours, France, ³³Hospital Center Sud Francilien, Corbeil-Essonnes, France, ³⁴Centre Hospitalier Pontoise, Pontoise, France, ³⁵Hospital Le Cluzeau, Limoges, France, ³⁶Bicetre Hospital, Le Kremlin-Bicêtre, France, ³⁷Hôpital Poissy, Poissy, France, ³⁸University Hospital of Saint-Étienne, Saint-Priest-en-Jarez, France, ³⁹Hospital Center De Cornouaille, Quimper, France, ⁴⁰Hospital Center De Versailles - Hospital André Mignot, Le Chesnay-Rocquencourt, France, ⁴¹Assistance Publique – Hôpitaux de Paris, Paris, France

Introduction: Preventing the occurrence of secondary progressive multiple sclerosis (SPMS) is one of the main challenges in managing MS patients.

Real-world data suggest that the early use of high-efficacy therapies (HET) may reduce the risk of transition to SPMS. However, current knowledge about predictive factors of long-term outcomes needs to be improved. The long-term prognostic value of reaching “No Evidence of Disease Activity” (NEDA) is controversial.

Objectives/Aims: The primary objective of this study is to determine baseline factors associated with the occurrence of SPMS in patients treated early with a HET.

Methods: This retrospective, multicentric study is based on the French MS Registry (OFSEP).

Patients who initiated a HET within the first 5 years after clinical MS onset, with an EDSS < 4, and who remained treated for at least 1 year were included.

Univariate analysis was performed to detect baseline variables associated with the risk of developing SPMS during follow-up. Identified variables were included in a multivariate analysis with a Cox proportional hazard model. The prognostic value of reaching NEDA at 1 year was also assessed. Type of treatment during follow-up was considered as time-varying covariate.

Results: 2237 patients were included in the analysis. At HET initiation: mean age 31.6 years, female/male sex ratio 2.3, median EDSS 2.0 (1.0-2.5), mean disease duration 2 yrs (SD 1.4), mean follow-up: 5.8yrs. The most prescribed HET were natalizumab (48.1%), fingolimod (36.2%), and ocrelizumab (13.7%).

At 5 years, 3.8% of patients developed SPMS. In univariate analysis, the following factors at baseline were associated with the occurrence of SPMS: male gender, older age, higher EDSS, and the use of oral HET. We did not find a significant association with the relapse rate before HET initiation or the NEDA status after 1 year of treatment.

After adjustment, we confirmed that female patients (HR 0.64, p=0.036) had a lower risk of developing SPMS than males. Older age (HR 2.26 in patients older than 30 compared to younger patients, p=0.003) with an EDSS >= 1 (HR 7.44, p<0.001) increased the risk, as well as the use of oral HET versus intravenous HET (HR 1.97, p=0.003)

Conclusion: In our study, 3.8% of patients who were early treated with a HET converted to SPMS, which is lower than expected compared to the known natural history of MS.

Introducing the HET in younger patients before any residual disability based on EDSS was associated with a lower risk of SPMS. Intravenous HET demonstrated a better prognosis compared to oral HET.

Disclosure of interest: Mikael Cohen received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ad Scientiam, Biogen, Merck, Sanofi-Genzyme, Roche, Celgene-BMS, Alexion, Horizon Therapeutics

Fabien Rollot: nothing to disclose

Marc Debouverie: nothing to disclose

Helene Zephir: nothing to disclose

Sandra Vukusic received grants, non- personal consulting fees and travel fees from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche and Sanofi.

Jerome De Seze: nothing to disclose

Pierre Labauge received honoriae / grants from Biogen, Novartis, Sanofi Genzyme, Roche, Novartis, Merck

Aurélie Ruet: nothing to disclose

Eric Berger: nothing to disclose

David Laplaud: nothing to disclose

Jonathan Ciron received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi, Roche, Celgene-BMS, Alexion, Horizon Therapeutics, none related to this study

Bertrand Bourre serves on scientific advisory board, has received funding for travel and honoraria from Alexion, Biogen, BMS, Horizon, Janssen, Merck, Novartis, Sanofi, and Roche.

Emmanuelle Le Page: nothing to disclose

Caroline Papeix: nothing to disclose

Eric Thouvenot: nothing to disclose

Abdullatif Al Khedr: nothing to disclose

Bruno Stankoff: nothing to disclose

Jean Pelletier: nothing to disclose

Elisabeth Maillart consulting or travel fees from Alexion, Biogen, Janssen, Novartis, Sanofi, Teva and Merck Serono, and research grant from Biogen, none related to the present work.

Olivier Casez: nothing to disclose

Thibault Moreau: nothing to disclose

Gilles Defer personal compensation for scientific advisory board from Biogen, BMS, Novartis, Genzyme, Roche and Teva pharmaceutical Industries Ltd. funding for travel and/or speaker honoraria from Merck Serono, Biogen, BMS, Novartis, Roche, Genzyme and Teva pharmaceutical Industries Ltd. His institution received grants supporting research for my department from Merck Serono, Biogen, Genzyme et Novartis

Pierre Clavelou: nothing to disclose

Philippe Cabre: nothing to disclose

Solène Moulin: nothing to disclose

Jean Philippe Neau: nothing to disclose

Wahab Abir: nothing to disclose

Karolina Hankiewicz: nothing to disclose

Inès Doghri: nothing to disclose

Haifa Ben Nasr: nothing to disclose

Corinne Pottier: nothing to disclose

Laurent Magy: nothing to disclose

Dalia Dimitri Boulos: nothing to disclose

Olivier Heinzlef: nothing to disclose

Jean Philippe Camdessanche: nothing to disclose

Marc Coustans: nothing to disclose

Chantal Nifle: nothing to disclose

David Brassat: nothing to disclose

Romain Casey: nothing to disclose

Christine Lebrun Frenay: nothing to disclose

Highly effective therapies as first-line treatments for pediatric onset multiple sclerosis in a French nationwide cohort

Nail Benallegue^1,2, Fabien ROLLOT^3,4,5,6, Sandrine Wiertlewski^2,7, Romain Casey^3,4,5,6, Marc Debouverie⁸, Emmanuelle Le Page⁹, Jérôme de Seze¹⁰, JONATHAN CIRON^11,12, Aurelie Ruet^13,14, Pierre Labauge¹⁵, Elisabeth Maillart¹⁶, Thi Helene ZEPHIR¹⁷, Caroline Papeix¹⁸, Gilles Defer¹⁹, Christine Lebrun-Frenay²⁰, Thibault Moreau²¹, Eric BERGER²², Bruno Stankoff²³, Pierre Clavelou²⁴, Olivier Heinzlef²⁵, Jean Pelletier²⁶, Eric Thouvenot^27,28, Abdullatif Al Khedr²⁹, Bertrand Bourre³⁰, Olivier Casez³¹, PHILIPPE CABRE³², ABIR WAHAB³³, Laurent Magy³⁴, Jean-Philippe Camdessanche³⁵, Inès Doghri³⁶, Solène Moulin³⁷, Haifa Khaled³⁸, Karolina Hankiewicz³⁹, JEAN PHILIPPE NEAU⁴⁰, céline labeyrie⁴¹, Dimitri Boulos Dalia⁴¹, Sandra Vukusic^3,4,5,6, David LAPLAUD^2,7

Study Group: OFSEP

¹CHU Angers, Univ Angers, Department of Pediatric Neurology, Angers, France, ²Nantes Université, CHU Nantes, INSERM, CIC 0004, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France, ³Université de Lyon, Université Claude Bernard, Lyon, France, ⁴Department of Neurology, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, sclérose en plaques, pathologies de la myéline et neuro-infammation, Bron, France, ⁵Centre de Recherche en Neurosciences de Lyon, Observatoire Français de La Sclérose en Plaques, INSERM 1028 et CNRS UMR 5292, Lyon, France, ⁶EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation, Bron, France, ⁷Department of Neurology, CHU Nantes, Nantes, France, ⁸Department of Neurology, Centre Hospitalier Régional Et Universitaire de Nancy, Université de Lorraine, Vandoeuvre-Lès-Nancy, France, ⁹Rennes University, CHU Rennes, CRC-SEP Neurology Department, CIC Inserm 1414, Rennes, France, ¹⁰Department of Neurology Et Centre d’Investigation Clinique, CHU de Strasbourg, INSERM 1434, Strasbourg, France, ¹¹Department of Neurology, CRC-SEP, CHU de Toulouse, Hôpital Pierre-Paul Riquet, Toulouse, France, ¹²Institut Toulousain Des Maladies Infectieuses Et Inflammatoires (Infinity), INSERM UMR 1291, CNRS UMR 5051, Université Toulouse III, Toulouse, France, ¹³Department of Neurology, CHU de Bordeaux, Bordeaux, France, ¹⁴14 Université de Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France, ¹⁵Department of Neurology, CHU de Montpellier, Montpellier, France, ¹⁶Department of Neurology, APHP, Hôpital Pitié-Salpêtrière, Paris, France, ¹⁷Pôle Des Neurosciences Et de L’appareil Locomoteur, CRC-SEP, Hôpital Roger Salengro, Université de Lille, Inserm U1172, Lille, France, ¹⁸Department of Neurology, Hôpital Fondation Adolphe de Rothschild, Paris, France, ¹⁹Department of Neurology, Centre Expert SEP, CHU de Caen, Université Normandie, Caen, France, ²⁰Department of Neurology, Neurologie Pasteur 2, CHU de Nice, Université Nice Cote d’Azur UR2CA-URRIS, Nice, France, ²¹Department of Neurology, Dijon, France, ²²Department of Neurology, CHU de Besançon, Besancon, France, ²³Department of Neurology, CHU Saint-Antoine, Paris, France, ²⁴Department of Neurology, CHU de Clermont-Ferrand, Clermont-Ferrand, France, ²⁵Département de Neurologie, Centre Hospitalier de Poissy, St Germain, France, ²⁶Aix Marseille Univ, APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie – MICeME, CRMBM CEMEREM UMR7339, Marseille, France, ²⁷Department of Neurology, CHU de Nîmes, Nîmes, France, ²⁸Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France, ²⁹Department of Neurology, CHU d’Amiens, Amiens, France, ³⁰CHU Rouen, Rouen, France, ³¹Department of Neurology, CHU de Grenoble, Grenoble, France, ³²Department of Neurology, CHU de Fort de France, Fort de France, France, ³³Department of Neurology, Assistance Publique des Hôpitaux de Paris, Hôpital Henri Mondor, Université Paris Est, Créteil, France, ³⁴Department of Neurology, CHU de Limoges, Limoges, France, ³⁵Department of Neurology, Hôpital Nord, CHU Saint-Étienne, St-Etienne, France, ³⁶Department of Neurology, CHU Tours, Tours, France, ³⁷Department of Neurology, CHU Reims, Reims, France, ³⁸Department of Neurology, Hôpital Sud Francilien, Corbeil Essonnes, France, ³⁹Department of Neurology, CH de Saint-Denis, Saint‑Denis, France, ⁴⁰Department of Neurology, CHU La Milétrie, Poitiers, France, ⁴¹Department of Neurology, CHU Bicêtre, Le Kremlin-Bicêtre, France

Introduction: Moderately-effective therapies (MET) have been the main treatment in pediatric- onset multiple sclerosis (POMS) for years. Despite the expanding use of highly-effective therapies (HET), therapeutic guidelines for POMS are missing.

Objectives/Aims: To assess the real-world effectiveness of HET as immediate treatment compared with MET on disease activity.

Methods: In this retrospective observational study, we used datafrom 36 French MS expert centers participating in the Observatoire Français de la Sclérose en plaques (OFSEP), the French MS registry. We included treatment-naïve children (aged under 18 years) with relapsing-remitting MS who initiated HET or MET from 2010 to 2022. We used an innovative statistical method to model the logarithm of event rates by a penalized splines of time, allowing the possibility to model the effects of covariates in a flexible way considering non-linearity and interactions.

Results: A total of 530 children were identified and met inclusion criteria (422 MET and 108 HET). Both HET and MET treatment strategies reduced the risk of first relapse within the first 2 years. HET dampened the occurrence of a first relapse with a 54% risk reduction compared to MET (adjusted Hazard Ratio HR 0.46 [95% CI 0.31-0.67]; p<0.001) and a sustained effect over 5 years of follow-up, confirmed on MRI activity (adjusted OR 0.34 [95% CI 0.18-0.66]; p=0.001) and with a better tolerability pattern. MET had six times more risk of discontinuation at 2 years (HR 5.97 [95% CI 2.92-12.20]). Index treatment was not associated with enrollment in tertiary education.

Conclusion: HET as first-line strategy in POMS reduces the occurrence of a first-relapse with an optimal effect within the two first-years compared to treatment escalation, supporting a need to use immediate HET in POMS.

Disclosure of interest: Both Benallegue N and Rollot F have contributed equally to this work.

Data collection has been supported by a grant provided by the French State and handled by the “Agence Nationale de la Recherche,” within the framework of the “France 2030” programme, under the reference ANR-10- COHO-002, Observatoire Français de la Sclérose en Plaques (OFSEP). We thank the Eugène Devic EDMUS Foundation against multiple sclerosis for support.

Benallegue N: nothing to disclose

Rollot F: nothing to disclose

Wiertlewski S : nothing to disclose

Casey R : nothing to disclose

Debouverie M : nothing to disclose

Le Page E : Advisory board for Biogen Idec, Novartis, Alexion, Merck, Roche; Presentations for Biogen Idec, Novartis, Merck, Roche.

De Sèze J : nothing to disclose

Ciron J : has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi, Roche, Celgene-BMS, Alexion, Horizon Therapeutics, none related to this study

Ruet A : I report no disclosure in relation with this study.I received funding for travel or speaker honoraria fromBiogen, Novartis, Roche, Alexion, Sanofi-Genzyme, and Merck. The institution received research support from Biogen, Sanofi-Genzyme and Roche outside the scope of this study.

Labauge P : nothing to disclose

Maillart E : (1) Alexion, funding for lecture fees.(2) Biogen, funding for travel and lecture fees (3) Bionure, funding for lecture fees(4) BMS, funding for lecture fees.(5) Merck, funding for travel and lecture fees(6) Novartis, funding for travel and lecture fees(7) Roche, funding for travel and lecture fees(8) Sanofi-Genzyme, funding for travel and lecture fees (9) Teva Pharmaceuticals, funding for travel and lecture fees

Zephir H : I received consulting fees from ROCHE, BIOGENIDEC, NOVARTIS, SANOFI, ALEXION, BMS. I received consultancies fees from BIOGENIDEC, MERCK, BAYER, NOVARTIS, SANOFI,BMS, ALEXION. I received research support grants from Ligue Francaise contre la sclerose en plaques (LFSEP) and from ARSEP (Association de recherche contre la Sclerose en plaques).

Papeix C : Funding for Travel or Speaker Honoraria from Novartis, Biogenteva, Roche, Merckbiogen Idec

Defer G : I received personal compensation for scientific advisory board from BiogenIdec, Novartis, BMS, Genzyme, Roche and Teva pharmaceutical Industries Ltd. I received funding for travel and/or speaker honoraria from Merck Serono, BiogenIdec, BMS, Novartis, Roche, Genzyme and Teva pharmaceutical Industries Ltd. My institution received grants supporting research for my department from Merck Serono, Biogen, Genzyme et Novartis.

Lebrun-Frenay C : Serving as editorial advisory board member for Revue Neurologique (Paris) Elsevier, Neurology and Therapy. Research Support, Academic Entities: UT Southwestern, Dallas, TX. Clinical advisor and senior professor; Research Support, Foundations and Societies: French MS Society (SFSEP), EDMUS (OFSEP Center) Foundation

Moreau T : Thibault Moreau reports receiving consulting fees and speaking fees from Biogen Idec, Sanofi Aventis, Genzyme, Teva Pharma, Bayer Schering, Merck Serono, Roche, Almirall and Novartis, Roche. Editorial Boards: la lettre du neurologue 2015 2021. I have been non-permanent consultant for biogen, genzyme, bayer-schering, novartis, teva, roche, Merck for board of research and speakers during meeting with the supports of these companies.

Berger E : Funding for Travel or Speaker Honoraria from Biogen Idec, for speaking; A ctelion, for speaking ; Genzyme, Board ; Novartis, Board and speaking; Merck, Board.

Stankoff B : scientific advisory boards for Novartis, Sanofi, Merck. Funding for Travel or Speaker Honoraria from Lectures for Biogen, Sanofi, Novartis, Merck, Janssen; Research grants from Merck Serono, Sanofi-Genzyme and Roche; Grants from Fondation ARSEP, fondation pour la recherche medicale (FRM), DGOS-APHP, PMSA, ANR, INSERM, ICM.

Clavelou P : Novartis (non profit entity)Teva Pharma (non profit entity)Merck (non profit entity)Biogen (non profit entity)Genzyme-Sanofi (non profit entity)Janssen (non profit entity)Roche (non profit entity). Funding for Travel or Speaker Honoraria : Non profit entity, fund directly to department of neurology : Novartis, Teva Pharma, Biogen, Merck, Bayer, Genzyme-Sanofi, Janssen, Roche. Editorial Advisory Board : La lettre du neurologue (french, no financial compensation, since fifteen years).

Heinzlef O : 1.Genzyme advisory Board2. Novartis advisory board3. Janssen advisory board; Funding for Travel or Speaker Honoraria from EdimarkEditorial Boards ; Lettre du neurologue. Consultancies: 1.Bayer Schering, 2.Merck, 3.Teva, 4.Genzyme, 5.Novartis, 6.Almirall, 7. Biogen Idec.

Pelletier J : nothing to disclose

Thouvenot E : Received honoraria for invited lectures from Biogen, Bristol Myers Squibb, Novartis, Merck-Serono, Roche, and Sanofi. Research Support from Biogen Idec; Novartis; PHRC national 2012 (NCT01817166); ARSEP.

Al-Khedr A : nothing to disclose

Bertrand Bourre serves on scientific advisory board, has received funding for travel and honoraria from Alexion, Biogen, BMS, Horizon, Janssen, Merck, Novartis, Sanofi, and Roche.

Casez O : Scientific Advisory Boards: (1) Biogen(2) Novartis(3) Genzyme(4) Roche(5) Merck; Funding for Travel or Speaker Honoraria: (1) Biogen (funding for travel, speaker honoraria)(2) Novartis (funding for travel, speaker honoraria)(3) Genzyme (funding for travel, speaker honoraria)(4) Roche (funding for travel, speaker honoraria)(5) Merck (speaker honoraria)

Cabre P: nothing to disclose

Wahab A : Compensation :received expert testimony from Roche and travel grants from Biogen

Magy L : Scientific advisory board: Alnylam Pfizer; Consulting or travel fees:CSL Behring Merck Sanofi

Camdessanché JP : Funding for Travel or Speaker Honoraria from Akcea, Alexion, Alnylam, Argenx, Biogen, Bristol Myers Squibb, CSL-Behring, Genzyme, Grifols, Laboratoire Francais des Biotechnologies, Merck-Serono, Novartis, Pfizer, Pharmalliance, Teva, UCB Pharma, Editions Scientifiques L&C, Edimark, Expression Sante, Natus, Scien, SNF-Floerger. Honoraria. Associate editor, Revue Neurologique (Paris). No compensation. Patent on anti-FGFR3 autoantibodies Patient on anti-AGO autoantibodies.

Godhri I: nothing to disclose

Moulin S : nothing to disclose

Nasr HB: nothing to disclose

Hankiewicz K: nothing to disclose

Neau JP: nothing to disclose

Labeyrie C : nothing to disclose

Dimitri Boulos D : nothing to disclose

Vukusic S : Scientific Advisory Boards: Biogen, BMS-Celgene, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, Teva. Funding for Travel or Speaker Honoraria: Biogen, BMS-Celgene, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, Teva. Consultancy in board for Biogen, BMS-Celgene, Janssen, Merck-Serono, Novartis, Roche, Sandoz, Sanofi-Genzyme. Research Support, Commercial Entities: Biogen, BMS-Celgene, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, Teva.

Laplaud DA : board membership, consultancy, and grants from Alexion, Actelion, BMS, Biogen, Merck, Novartis, Roche, and Sanofi.

Can we reduce the risk of MS conversion? Radiologically Isolated syndrome

Christine Lebrun-Frenay¹

¹Université Nice Cote d'azur, Neurologie, nice, France

Introduction: Even before the introduction of RIS criteria, longitudinal clinical data from individuals with incidentally identified T2 lesions suggestive of multiple sclerosis (MS) were described. Healthy individuals who do not exhibit signs of neurological dysfunction commonly have brain MRI studies performed for a reason other than an evaluation for MS that reveal unexpected anomalies highly suggestive of demyelinating plaques, given their size, location, and morphology.

Objectives/Aims: These healthy subjects lack symptomatology suggestive of MS and fulfill formal criteria for the radiologically isolated syndrome (RIS). This recently described MS subtype expands upon the phenotype of at-risk individuals for future demyelinating events. A formal description of RIS was first introduced in 2009 by Okuda et al. to define this relevant cohort of individuals at risk for future demyelinating events.

Methods: In European or North American observational studies, the authors have found that up to 30-45% of patients presenting with a RIS will show clinical progression. The presence of asymptomatic lesions in the cervical cord increases the risk of progression, either to relapsing or to progressive MS.

The consortium studying the epidemiology of RIS worldwide (RISC) presented its first retrospective cohort. The 5-year and 10-year observed conversion rates to the first clinical event were 34% and 51%. In the multivariate model, age, sex (male), oligoclonal bands, and lesions within the spinal cord were identified as significant predictors for developing a first clinical event.

Results: The ARISE study demonstrated the efficacy of dimethyl fumarate on the occurrence of a clinical event, with a decreased risk of over 80% to evolve to MS for the treated arm. The TERIS study evaluating the efficacy of teriflunomide in RIS showed a risk reduction of 63% over placebo. These two results significantly advance our conviction that early treatment for MS is necessary and potentially impacts long-term disability.

Conclusion: Despite advancements in the characterization of RIS subjects and our understanding of risk factors for initial symptom development, we need to define risk profiles for a seminal neurological event to propose treatment to at-risk RIS subjects.

Disclosure of interest: none

Retrouvez-nous à l'ECTRIMS 2024, du 18 au 20 septembre 2024.