Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 13/10/2023
• Auteurs : Jérémie DamayTobias BenderChristoph MunkMichael JousserandMilena CretonEmmanuel FredonRomain RémondPierre Jean MeausooneAlexander PfriemPhilippe Gerardin
• Organismes : Laboratoire d'Etudes et de Recherche sur le Matériau Bois Eberswalde University for Sustainable Development Eberswalde University for Sustainable Development Buffet Crampon Buffet Crampon Laboratoire d'Etudes et de Recherche sur le Matériau Bois Laboratoire d'Etudes et de Recherche sur le Matériau Bois Laboratoire d'Etudes et de Recherche sur le Matériau Bois Eberswalde University for Sustainable Development Laboratoire d'Etudes et de Recherche sur le Matériau Bois
• Publié dans European Journal of Wood and Wood Products le 26/10/2020

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Résumé : Most European hardwoods are nowadays under-utilized due to drawbacks such as low dimensional stability, durability and surface hardness. Seven hardwood species were thermally and/or chemically modified in order to improve these disadvantages. Heat treatment was carried out in air at atmospheric pressure at three temperatures, while two types of chemical modifications were tested, the first being based on furfuryl alcohol with tartaric acid, the second being based on succinic anhydride and glycerol. Then, modified woods were studied to determine weight loss due to thermal treatment, solution uptake, weight percent gain and swelling due to chemical modification processes. After that, main properties of chemically modified woods were characterized including density, equilibrium moisture content, dimensional stability and surface hardness. Effect of thermal pretreatment on subsequent chemical modification and on properties of modified woods obtained have also been evaluated. Combination of thermal modification with chemical modification had led to better improvements than each separately. Furfurylation treatment appeared to be more efficient than polyester modification. Most of the modified samples were denser, more stable and harder than native wood. These modified woods might compete with imported tropical wood for applications requiring high stability and hardness, such as joinery, decking or flooring, music instruments, handles for tools or kitchen utensils.

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• Type de publi. : Article dans une revue
• Date de publi. : 13/10/2023
• Auteurs : Thiébaud PicartJohan PalludJulien BerthillerChloé DumotMoncef BerhoumaFrancois DucrayXavier ArmoiryJennifer MargierPascale GuerrePascale VarletDavid MeyronetPhilippe MetellusJacques GuyotatElsa MagroPhilippe MeneiHugues LoiseauHenri DufourNicolas ReynsMichel LonjonEdouard GimbertEvelyne EmeryWalid FarahFrançois VassalPierre Jean Le ResteIlyes ZemmouraLuc BauchetOlivier LangloisFabrice ParkerEmmanuel MandonnetFaillot ThierryRémy GuillevinLuc TaillandierAnne TermozNathalie PerretonEstelle Bravant
• Organismes : Hospices Civils de Lyon
• Publié dans Journal of Neurosurgery le 26/10/2020

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Résumé : OBJECTIVE Only one phase III prospective randomized study, published in 2006, has assessed the performance of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) for glioblastoma resection. The aim of the RESECT study was to compare the onco-functional results associated with 5-ALA fluorescence and with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care. METHODS This was a phase III prospective randomized single-blinded study, involving 21 French neurosurgical centers, comparing 5-ALA FGS with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care, including neuronavigation use and postoperative radiochemotherapy. Randomization was performed in a 1:1 ratio stratified by institution. 5-ALA (20 mg/kg) or placebo (ascorbic acid) was administered orally 3-5 hours before the incision. The primary endpoint was the rate of gross-total resection (GTR) blindly assessed by an independent committee. Patients without a confirmed pathological diagnosis of glioblastoma or with unavailable postoperative MRI studies were excluded from the per-protocol analysis. RESULTS Between March 2013 and August 2016, a total of 171 patients were assigned to the 5-ALA fluorescence group (n = 88) or to the placebo group (n = 83). Twenty-four cases were excluded because the WHO histological criteria of grade 4 glioma were not met. The proportion of GTR was significantly higher in the 5-ALA fluorescence group (53/67, 79.1%) than in the placebo group (33/69, 47.8%; p = 0.0002). After adjustment for age, preoperative Karnofsky Performance Scale score, and tumor location, GTR was still associated with 5-ALA fluorescence (OR 4.13 [95% CI 1.94-8.79]). The mean 7-day postoperative Karnofsky Performance Scale score (≥ 80% in 49/71, 69.0% [5-ALA group]; 50/71, 70.4% [placebo group], p = 0.86) and the proportion of patients with a worsened neurological status 3 months postoperatively (9/68, 13.2% [5-ALA group]; 9/70, 12.9% [placebo group], p = 0.95) were similar between groups. Adverse events related to 5-ALA intake were rare and consisted of photosensitization in 4/87 (4.6%) patients and hepatic cytolysis in 1/87 (1.1%) patients. The 6-month PFS (70.2% [95% CI 57.7%-79.6%] and 68.4% [95% CI 55.7%-78.1%]; p = 0.39) and 24-month OS (30.1% [95% CI 18.9%-42.0%] and 37.7% [95% CI 25.8%-49.5%]; p = 0.89) did not significantly differ. In multivariate analysis, GTR was an independent predictor of PFS (hazard ratio 0.56 [95% CI 0.36-0.86], p =

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• Type de publi. :
• Date de publi. : 13/10/2023
• Auteurs : Philippe PierratPierre MagriJean-Jacques Gaumet
• Organismes : Laboratoire Lorrain de Chimie Moléculaire Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes

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• Type de publi. : Chapître d'ouvrage
• Date de publi. : 13/10/2023
• Auteurs : Carine CalastrencFrançois BaleuxNicolas PoirierChristine RenduPierre CampmajoNicolas DobigeonNicolas MelladoClaire Marais-SicreMarie-Claude BalMagalie PhillippeMuriel Llubes
• Organismes : Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés France, Amériques, Espagne, Sociétés, Pouvoirs, Acteurs Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés France, Amériques, Espagne, Sociétés, Pouvoirs, Acteurs Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés Signal et Communications Institut National Polytechnique (Toulouse) Centre National de la Recherche Scientifique Structural Models and Tools in Computer Graphics Centre d'études spatiales de la biosphère Géographie de l'environnement Géographie de l'environnement Géosciences Environnement Toulouse

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Résumé : It took several decades of interaction and dialogue between human sciences and environmental sciences and a number of methodological advances for high altitude spaces to be considered as something other than immutable and atonic. Subjected to integrated interdisciplinary questioning, they reveal not one, but many complex histories and dynamics. By historicising mountain areas, the global point of view on societies is reversed and the whole of the valley systems are reconsidered. It is clear that the teams involved in this research are faced with the problem of acquiring primary information. An essential prerequisite for any archaeological research, high mountain prospecting has its own specificities and particular methodological challenges. How can we go beyond the threshold of the visible surface (micro-relief elevation) to enrich the information with infrastructures made of perishable materials or covered by vegetation? How can we systematise the acquisition to be able to process larger territories more quickly?Technological advances (photogrammetry, thermography, Lidar, georadar, magnetometer, chemical analysis of soils), the diversification and miniaturisation of sensors, the democratisation and development of aerial drones, which allow for the repeatability of acquisitions, are opening up the possibility of setting up new archaeological information acquisition procedures. The new data processing tools, the work on software ergonomics and the opening up of the field of possibilities offered by artificial intelligence allow us to foresee new possibilities for optimising the detection of archaeological remains in high altitude environments.

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Fichiers liés : Article_Colloque_Nice_2022_Prog_TAHMM.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 13/10/2023
• Auteurs : Timothée BruelLou-Léna VrignaudFrançoise PorrotIsabelle StaropoliDelphine PlanasFlorence Guivel-BenhassineJulien PuechMatthieu ProtSandie MunierWilliam Henry BollandCathia SouliéKaren ZafilazaKaren ZafilazaClovis Lusivika-NzingaMarie-Laure MeledgeCéline DorivalDiana MolinoHélène PéréYouri YordanovEtienne Simon-LoriereDavid VeyerFabrice CarratOlivier SchwartzAnne-Geneviève MarcelinGuillaume Martin-BlondelMagalie GarciaValentin GiraudAgathe MetaisThomas GabasNaima HadjadjCélia SalanoubatAmélie ChabrolPierre HoussetAgathe PardonAnne-Laure FauconValérie CaudwellLaurent AlricGrégory PugnetMorgane MourguetEva BoriesDelphine BonnetSandrine CharpentierPierre DelobelAlexa DebardColleen BeckXavier BoumazaClaire DelageElisabete Gomes PiresMorgane CheminantMélanie CrestaMarine NadalMartin SiguierMarwa BachirCléa MelenotteAntoine FaycalVincent BerotCécile BrinSiham DjebaraStéphane MarotSophie SayonVincent LeducqIsabelle MaletElisa TeyssouYasmine Abi AadThibault ChiarabiniRaynald FelihoNadia ValinFabien BrigantJulien BoizePierre-Clément ThiébaudMarie MoreauGeoffroy LiégeonBlandine DenisJean-Michel MolinaLucia EtheveSylvie AbelOrnella CabrasKarine GuitteaudDiama NdiayeJonathan PehlivanMichael PhelippeauThierry PistoneArnaud DesclauxDidier NeauBenjamin FestouMagali Dupuy-GrassetVéronique Loustaud-RattiChristophe ChoquetOlivia da ConceicaoMichael ThyLio CollasCindy GodardDonia BouzidVittiaroat IngLaurent PereiraThomas PavlowskyCamille Ravautantoine Asquier-KhatiDavid BoutoilleMarie ChauveauColin DeschanvresMarine CailleauxFrançois BenezitAnne MaillardBenoit HueClaudia Carvalho-SchneiderSimon JamardLaeticia PetitClément TheisMagali VidalLéo SauvatGuillaume BaronnetThomas PerpointAnne ConradPaul ChabertPaul LoubetJulien MazetR. LarcherAmos WoerlenAline RemillonLaure Absensur-VuillaumeKaren DelavignePierre CougoulJérémie DionThibault SixtFlorian MorettoCarole CharlesLydia LegerArulvani ArulananthanCarine LascouxPascaline ValérieVentzislava Petrov-SanchezAlpha DialloSoizic Le MestreFrédéric ChauBrahim SoltanaJessica Chane TangJérémie GuedjYvanie CailleAnthony ChauvinNathalie ChavarotXavier EyerVéronique DelceySimon BessisRomain GueneauPélagie ThibautChristia PalaciosValérie PourcherKarine LacombeAdélie GothlandCharlotte BillardNathalie de CastroAndré CabiéVincent DubéeSandrine PierreAnne-Marie RonchettiJean-Philippe MartellosioRoland S LiblauLatifa HanafiFanny LanternierStella RoussetRafaël MahieuAlexandre DuvignaudFrance RoblotCharles CazanaveJean-François FaucherDelphine ChainierNathan Peiffer-SmadjaFrançois RaffiAudrey Le BotPierre TattevinFrançois CoustillèresNatacha MrozekKarl SteficBenjamin LefèvreFlorence AderAgnès DidierDelphine MartineauPierre ChauvelotAurélie MartinDidier LaureillardMathilde DevauxJérôme FreyPauline BouquetAlbert Trinh-DucPatrick RispalPhilippe PetuaJulien CarilloAurore PerrotOdile RauzyMathieu BlotLionel PirothSophie CircostaLeia BecamGuillaume Le MeutIsabelle GoderelYazdan Yazdanpanah
• Organismes : Virus et Immunité - Virus and immunity Vaccine Research Institute [Créteil, France] Virus et Immunité - Virus and immunity Vaccine Research Institute [Créteil, France] Sorbonne Université Virus et Immunité - Virus and immunity Virus et Immunité - Virus and immunity Virus et Immunité - Virus and immunity Vaccine Research Institute [Créteil, France] Virus et Immunité - Virus and immunity Hôpital Européen Georges Pompidou [APHP] Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses Virus et Immunité - Virus and immunity École Doctorale Bio Sorbonne Paris Cité [Paris] Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Pitié-Salpêtrière [AP-HP] Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Pitié-Salpêtrière [AP-HP] Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Pitié-Salpêtrière [AP-HP] Institut Pierre Louis d'Epidémiologie et de Santé Publique Institut Pierre Louis d'Epidémiologie et de Santé Publique Institut Pierre Louis d'Epidémiologie et de Santé Publique ANRS - Maladies infectieuses émergentes Hôpital Européen Georges Pompidou [APHP] Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Saint-Antoine [AP-HP] Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses Centre National de Référence des virus respiratoires (dont la grippe et le SARS-CoV2) [Paris] Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses Hôpital Européen Georges Pompidou [APHP] Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Saint-Antoine [AP-HP] Virus et Immunité - Virus and immunity Vaccine Research Institute [Créteil, France] Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Saint-Antoine [AP-HP] Service Maladies infectieuses et tropicales [CHU Toulouse] Institut Toulousain des Maladies Infectieuses et Inflammatoires Université de Lorraine INterdisciplinarité en Santé Publique Interventions et Instruments de mesure complexes Faculté de Médecine [Nancy] Centre Hospitalier Régional Universitaire de Nancy Service des Maladies Infectieuses et Tropicales [CHRU Nancy]
• Publié dans Med le 16/06/2022

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Résumé : Antibodies effective against the recent Omicron sublineages are missing. By taking advantage of a multi-centric prospective cohort of immunocompromised individuals treated for mild-to-moderate COVID-19, Bruel et al. show that administration of 500 mg of sotrovimab induces serum neutralization and antibody-dependent cellular cytotoxicity of BQ.1.1 and XBB.1.5. Therefore, sotrovimab may remain a therapeutic option against these variants.

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Fichiers liés : 2023-07-17 ms letter HAL.pdf

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• Type de publi. :
• Date de publi. : 12/10/2023
• Auteurs : Philippe PierratPierre MagriJean-Jacques Gaumet
• Organismes : Laboratoire Lorrain de Chimie Moléculaire Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes

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• Type de publi. : Article dans une revue
• Date de publi. : 12/10/2023
• Auteurs : Daniela Rodrigues-BrazLinxin ZhuEmmanuelle GélizéJean-Pierre ClarinXavier ChatagnonYoucef BenzinePhilippe RampignonAgathe ThouveninJean-Louis BourgesFrancine Behar-CohenMin Zhao
• Organismes : Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers Unité de Technologies Chimiques et Biologiques pour la Santé Agence Générale des Equipements et Produits de Santé [Paris] Centre de Recherche des Cordeliers Hôpital Cochin [AP-HP] Centre de Recherche des Cordeliers Hôpital Cochin [AP-HP] Hôpital Foch [Suresnes] Centre de Recherche des Cordeliers
• Publié dans Pharmaceuticals le 26/10/2020

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Résumé : Abnormal corneal wound healing can compromise corneal transparency and lead to visual impairment. Mineralocorticoid receptor antagonists (MRA) are promising candidates to promote corneal remodeling with anti-inflammatory properties and lack gluococorticoids-associated side effects. In this preclinical study, a new polymer-free hydroxypropyl-gamma-cyclodextrin-based eyedrop containing 0.1% spironolactone (SPL), a potent but non-water-soluble MRA, was investigated for its ocular surface tolerance and efficacy in a rat model of corneal wound healing. SPL eyedrops were stable for up to 9 months at 4 °C. The formulation was well-tolerated since no morphological changes or inflammatory reactions were observed in the rat cornea after multiple daily instillations over 7 days. SPL eyedrops accelerated rat corneal wound healing, reduced corneal edema and inflammation, enhanced epithelial integrity, and improved nerve regeneration, suggesting restoration of corneal homeostasis, while potassium canrenoate, an active and soluble metabolite of SPL, had no effect. SPL eyedrops could benefit patients with impaired corneal wound healing, including that secondary to glucocorticoid therapy. Repurposing known drugs with known excipients will expedite translation to the clinic.

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• Type de publi. : Communication dans un congrès
• Date de publi. : 11/10/2023
• Auteurs : Mikael CohenFabien RollotMarc DebouverieHélène ZéphirSandra VukusicJérôme de SèzePierre M. LabaugeAurélie RuetÉric BergerDavid-Axel LaplaudJ CironBertrand BourreEmmanuelle Le PageCaroline PapeixEric ThouvenotAbdullatif Al KhedrBruno StankoffJean PelletierElisabeth MaillartOlivier CasezThibault MoreauGilles DeferPierre ClavelouPhilippe CabreSolène MoulinJean-Philippe NeauAbir WahabKarolina HankiewiczInès DoghriHaifa KhaledCorinne PottierLaurent MagyDalia Meshaka-Dimitri-BoulosDimitri BoulosOlivier HeinzlefJean-Philippe CamdessanchéMarc CoustansChantal NifleDavid BrassatRomain CaseyChristine Lebrun-Frenay
• Organismes : Centre Hospitalier Universitaire de Nice Université Claude Bernard Lyon 1 Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Centre Hospitalier Universitaire de Nancy Centre Hospitalier Régional Universitaire [CHU Lille] Université Claude Bernard Lyon 1 Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Centre Hospitalier Universitaire [Strasbourg] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Toulouse Institut Toulousain des Maladies Infectieuses et Inflammatoires CHU Rouen Centre d'Investigation Clinique [Rennes] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] CHU Amiens-Picardie Aix Marseille Université Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Centre hospitalier universitaire de Poitiers = Poitiers University Hospital CHU Henri Mondor [Créteil] Centre Hospitalier Régional Universitaire de Tours CHU Limoges Université Claude Bernard Lyon 1 Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Centre Hospitalier Universitaire de Nice

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• Type de publi. : Article dans une revue
• Date de publi. : 11/10/2023
• Auteurs : Elise DreanoPierre-Régis BurgelAurélie HattonNaim BouazzaBenoit ChevalierJulie MaceySylvie LeroyIsabelle DurieuLaurence WeissDominique GrenetNathalie StremlerCamille OhlmannPhilippe ReixMichele PorzioPauline Roux ClaudeNatacha RémusBenoit DouvrySylvie MontcouquiolLaure CossonJulie MankikianJeanne LanguepinVeronique HoudouinLaurence Le ClaincheAnne GuillaumotDelphine PouradierAdrien TissotPascaline PriouLaurent MélyFrederique ChedevergneMuriel LebourgeoisJean LebihanClémence MartinFlora ZavalaJennifer da SilvaLydie LemonnierMairead Kelly-AubertAnita GolecPierre FoucaudChristophe MarguetAleksander EdelmanAlexandre HinzpeterPaola de CarliEmmanuelle GirodonIsabelle Sermet-GaudelusIwona Pranke
• Organismes : Institut Necker Enfants-Malades Institut Cochin Institut Necker Enfants-Malades Institut Necker Enfants-Malades Hospices Civils de Lyon Institut Necker Enfants-Malades Institut Necker Enfants-Malades Institut Necker Enfants-Malades Institut Necker Enfants-Malades Institut Necker Enfants-Malades Institut Necker Enfants-Malades Institut Necker Enfants-Malades Institut Necker Enfants-Malades
• Publié dans European Respiratory Journal le 23/10/2020

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Résumé : Background Around 20% of people with cystic fibrosis (pwCF) do not have access to the triple combination elexacaftor/tezacaftor/ivacaftor (ETI) in Europe because they do not carry the F508del allele on the CF transmembrane conductance regulator ( CFTR ) gene. Considering that pwCF carrying rare variants may benefit from ETI, including variants already validated by the US Food and Drug Administration (FDA), a compassionate use programme was launched in France. PwCF were invited to undergo a nasal brushing to investigate whether the pharmacological rescue of CFTR activity by ETI in human nasal epithelial cell (HNEC) cultures was predictive of the clinical response. Methods CFTR activity correction was studied by short-circuit current in HNEC cultures at basal state (dimethyl sulfoxide (DMSO)) and after ETI incubation and expressed as percentage of normal (wild-type (WT)) CFTR activity after sequential addition of forskolin and Inh-172 (Δ I ETI/DMSO %WT). Results 11 pwCF carried variants eligible for ETI according to the FDA label and 28 carried variants not listed by the FDA. ETI significantly increased CFTR activity of FDA-approved CFTR variants (I601F, G85E, S492F, M1101K, R347P, R74W;V201M;D1270N and H1085R). We point out ETI correction of non-FDA-approved variants, including N1303K, R334W, R1066C, Q552P and terminal splicing variants (4374+1G>A and 4096-3C>G). Δ I ETI/DMSO %WT was significantly correlated to change in percentage predicted forced expiratory volume in 1 s and sweat chloride concentration (p<0.0001 for both). G85E, R74W;V201M;D1270N, Q552P and M1101K were rescued more efficiently by other CFTR modulator combinations than ETI. Conclusions Primary nasal epithelial cells hold promise for expanding the prescription of CFTR modulators in pwCF carrying rare mutants. Additional variants should be discussed for ETI indication.

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• Type de publi. : Communication dans un congrès
• Date de publi. : 11/10/2023
• Auteurs : Naïl BenallegueFabien RollotS WiertlewskiRomain CaseyMarc DebouverieEmmanuelle Le PageJérôme de SèzeJonathan CironAurélie RuetPierre M. LabaugeElisabeth MaillartThi Helene ZephirCaroline PapeixGilles-Louis DeferChristine Lebrun-FrenayThibault MoreauEric BergerBruno StankoffPierre ClavelouOlivier HeinzlefJean PelletierEric ThouvenotAbdullatif Al KhedrBertrand BourreOlivier CasezPhilippe CabreAbir WahabLaurent MagyJean-Philippe CamdessanchéInès DoghriSolène MoulinHaifa KhaledKarolina HankiewiczJean-Philippe NeauCéline LabeyrieDalia Dimitri BoulosSandra VukusicDavid-Axel Laplaud
• Organismes : Centre Hospitalier Universitaire d'Angers Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Fondation Eugène Devic EDMUS Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Fondation Eugène Devic EDMUS Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL] Service de neurologie [CHRU Nancy] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre d'Investigation Clinique [Rennes] CIC Strasbourg Service de Neurologie [Strasbourg] Institut Toulousain des Maladies Infectieuses et Inflammatoires Département Neurologie [CHU Toulouse] Centre d'investigation clinique de Toulouse Centre Hospitalier Universitaire de Bordeaux Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale Département de Neurologie [Hôpital Gui de Chauliac - CHU Montpellier] CHU Pitié-Salpêtrière [AP-HP] Hôpital Roger Salengro [Lille] Centre de Ressources et de Compétences sur la Sclérose en Plaques (CRC-SEP) [Lille] Hôpital Fondation Adolphe de Rothschild = Adolphe de Rothschild Foundation Hospital Service de Neurologie [CHU Caen] Centre de Ressources et de Compétences sur la Sclérose en Plaques (CRC-SEP) [Caen] Service de Neurologie [CHU Nice] Unité de Recherche Clinique Côte d’Azur Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon) Service de Neurologie [CHRU Besançon] CHU Saint-Antoine [AP-HP] Service Neurologie [CHU Clermont-Ferrand] Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy] Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] Institut de Génomique Fonctionnelle Service de Neurologie [CHU Nimes] Service de neurologie [Amiens] CHU Rouen CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique] Hôpital Henri Mondor Service de Neurologie [CHU Limoges] Service de Neurologie [CHU de Saint-Étienne] Centre Hospitalier Régional Universitaire de Tours Service de neurologie [Reims] Centre Hospitalier Sud Francilien - Centre Hospitalier d'Evry Centre Hospitalier de Saint-Denis [Ile-de-France] Service de neurologie [CHU de Poitiers] Service de neurologie [Le Kremlin Bicêtre] Service de neurologie [Le Kremlin Bicêtre] Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Fondation Eugène Devic EDMUS Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital

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Résumé : 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.

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