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Disease modifying therapies and disease activity during pregnancy and postpartum in a contemporary cohort of relapsing Multiple Sclerosis patients

  • Author Footnotes
    1 Co-first authors.
    Lucile Lescot
    Footnotes
    1 Co-first authors.
    Affiliations
    Neurology Department, CRCSEP, Rennes Clinical Investigation Centre CIC-P 1414, Service de Neurologie, CHU Pontchaillou, Rennes University Hospital Rennes University INSERM, Rennes 35033, France
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  • Author Footnotes
    1 Co-first authors.
    Mathilde Lefort
    Footnotes
    1 Co-first authors.
    Affiliations
    EHESP, CNRS, Inserm, Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, University Rennes, Rennes F-35000, France
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  • Soizic Leguy
    Affiliations
    Neurology Department, CRCSEP, Rennes Clinical Investigation Centre CIC-P 1414, Service de Neurologie, CHU Pontchaillou, Rennes University Hospital Rennes University INSERM, Rennes 35033, France
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  • Emmanuelle Le Page
    Affiliations
    Neurology Department, CRCSEP, Rennes Clinical Investigation Centre CIC-P 1414, Service de Neurologie, CHU Pontchaillou, Rennes University Hospital Rennes University INSERM, Rennes 35033, France
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  • Sandra Vukusic
    Affiliations
    Service de neurologie, Sclérose en plaques, Pathologies de la myéline et neuro-inflammation et centre de recherche, Ressources et compétences sur la sclérose en plaques, Hospices civils de Lyon, Bron 69677, France

    Inserm 1028 et CNRS UMR 5292, Observatoire français de la sclérose en plaques, Centre de recherche en neurosciences de Lyon, Lyon 69003, France

    Université de Lyon, Université Claude-Bernard Lyon 1, Lyon 69000, France

    Eugène Devic EDMUS Foundation against multiple sclerosis, State-approved foundation, Bron 69677, France
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  • Gilles Edan
    Affiliations
    Neurology Department, CRCSEP, Rennes Clinical Investigation Centre CIC-P 1414, Service de Neurologie, CHU Pontchaillou, Rennes University Hospital Rennes University INSERM, Rennes 35033, France
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  • Anne Kerbrat
    Affiliations
    Neurology Department, CRCSEP, Rennes Clinical Investigation Centre CIC-P 1414, Service de Neurologie, CHU Pontchaillou, Rennes University Hospital Rennes University INSERM, Rennes 35033, France
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  • Christine Lebrun-Frenay
    Affiliations
    CRCSEP, CHU de Nice Pasteur 2, Université Nice Côte d'Azur UR2CA URRIS, Nice, France
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  • Jérome De Sèze
    Affiliations
    Centre d'investigation clinique, INSERM U1434, Centre Hospitalier Universitaire de Strasbourg, 1 Place de l'Hôpital, Strasbourg 67000, France
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  • David Axel Laplaud
    Affiliations
    Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
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  • Sandrine Wiertlewski
    Affiliations
    Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
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  • Author Footnotes
    2 Co-last authors.
    Emmanuelle Leray
    Footnotes
    2 Co-last authors.
    Affiliations
    EHESP, CNRS, Inserm, Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, University Rennes, Rennes F-35000, France
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  • Author Footnotes
    2 Co-last authors.
    Laure Michel
    Correspondence
    Corresponding author at: Neurology Department, CRCSEP, Rennes Clinical Investigation Centre CIC-P 1414, Service de Neurologie, CHU Pontchaillou, Rennes University Hospital Rennes University INSERM, Rennes 35033, France.
    Footnotes
    2 Co-last authors.
    Affiliations
    Neurology Department, CRCSEP, Rennes Clinical Investigation Centre CIC-P 1414, Service de Neurologie, CHU Pontchaillou, Rennes University Hospital Rennes University INSERM, Rennes 35033, France

    Microenvironment, Cell Differentiation, Immunology and Cancer unit, INSERM, Rennes I University, French Blood Agency, Rennes, France
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  • Author Footnotes
    1 Co-first authors.
    2 Co-last authors.
Published:August 15, 2022DOI:https://doi.org/10.1016/j.msard.2022.104122

      Abstract

      Background

      In Multiple Sclerosis (MS) women, therapeutic management for pregnancy planning and during pregnancy still represents a challenge regarding timing of disease-modifying therapies (DMT) stop, risk of disease reactivation and potential fetal toxicity. The objective of this study was to describe disease activity during pregnancy and postpartum depending on treatment status before conception in women with MS.

      Methods

      339 MS patients who have achieved a pregnancy between 2007 and 2017 were included. Women were classified according to their exposure to DMT in the 18 months period prior to pregnancy (untreated / first- / second/third-line treatment).

      Results

      122 women were not exposed to DMT prior to conception, whereas 147 were exposed to first-line DMT and 70 to second/third line DMT (73% to natalizumab and 23% to fingolimod) before conception. In the first-line group, the ARR decreased from 0.39 during the year before conception to 0.21 during pregnancy, whereas it increased in the second/third-line group from 0.59 to 0.78. 47.1% of the second/third-line group faced at least one relapse during pregnancy and the time from conception to first relapse was significantly shorter in this group (p < 10−4). The risk of relapse during pregnancy and postpartum was associated with occurrence of pre-conception relapses and second/third line DMT exposure before pregnancy.

      Conclusion

      Careful consideration should be given to natalizumab and fingolimod exposed patients before conception as they are at higher risk of reactivation of MS during pregnancy.

      Keywords

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      References

        • Alroughani R.
        • Alowayesh M.S.
        • Ahmed S.F.
        • Behbehani R.
        • Al-Hashel J.
        Relapse occurrence in women with multiple sclerosis during pregnancy in the new treatment era.
        Neurology. 2018; 90: e840-e846
        • Bianco A.
        • Lucchini M.
        • Totaro R.
        • Fantozzi R.
        • De Luca G.
        • Di Lemme S.
        • et al.
        Disease reactivation after fingolimod discontinuation in pregnant multiple sclerosis patients.
        Neurother. J. Am. Soc. Exp. Neurother. 2021; 18 ([Internet] Available from:): 2598-2607
        • Bsteh G.
        • Algrang L.
        • Hegen H.
        • Auer M.
        • Wurth S.
        • Di Pauli F.
        • et al.
        Pregnancy and multiple sclerosis in the DMT era: a cohort study in Western Austria.
        Mult. Scler. 2020; 26 ([Internet] Available from:): 69-78
        • Confavreux C.
        • Compston D.A.
        • Hommes O.R.
        • McDonald W.I.
        • Thompson A.J.
        EDMUS, a European database for multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 1992; 55 ([Internet]Feb 16Available from:): 671-676
        • Confavreux C.
        • Hutchinson M.
        • Hours M.M.
        • Cortinovis-Tourniaire P.
        • Moreau T.
        Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in multiple sclerosis group.
        N. Engl. J. Med. 1998; 339 ([Internet] Available from:): 285-291
        • De Giglio L.
        • Gasperini C.
        • Tortorella C.
        • Trojano M.
        • Pozzilli C.
        Natalizumab discontinuation and disease restart in pregnancy: a case series.
        Acta Neurol. Scand. 2015; 131 ([Internet] Available from:): 336-340
        • Demortiere S.
        • Rico A.
        • Maarouf A.
        • Boutiere C.
        • Pelletier J.
        • Audoin B.
        Maintenance of natalizumab during the first trimester of pregnancy in active multiple sclerosis.
        Mult. Scler. 2020; ([Internet]1352458520912637Available from:)
        • Finkelsztejn A.
        • Fragoso Y.D.
        • Ferreira M.L.B.
        • Lana-Peixoto M.A.
        • Alves-Leon S.V.
        • Gomes S.
        • et al.
        The Brazilian database on pregnancy in multiple sclerosis.
        Clin. Neurol. Neurosurg. 2011; 113 ([Internet] Available from:): 277-280
        • Hellwig K.
        • Haghikia A.
        • Rockhoff M.
        • Gold R.
        Multiple sclerosis and pregnancy: experience from a nationwide database in Germany.
        Ther. Adv. Neurol. Disord. 2012; 5 ([Internet] Available from:): 247-253
        • Hughes S.E.
        • Spelman T.
        • Gray O.M.
        • Boz C.
        • Trojano M.
        • Lugaresi A.
        • et al.
        Predictors and dynamics of postpartum relapses in women with multiple sclerosis.
        Mult. Scler. 2014; 20 ([Internet] Available from:): 739-746
        • Jesus-Ribeiro J.
        • Correia I.
        • Martins A.I.
        • Fonseca M.
        • Marques I.
        • Batista S.
        • et al.
        Pregnancy in multiple sclerosis: a portuguese cohort study.
        Mult Scler Relat Disord. 2017; 17 ([Internet] Available from:): 63-68
        • Kleerekooper I.
        • van Kempen Z.L.E.
        • Leurs C.E.
        • Dekker I.
        • Rispens T.
        • Lissenberg-Witte B.I.
        • et al.
        Disease activity following pregnancy-related discontinuation of natalizumab in MS.
        Neurol. Neuroimmunol. Neuroinflamm. 2018; 5 ([Internet] Available from:): e424
        • Langer-Gould A.
        • Smith J.B.
        • Albers K.B.
        • Xiang A.H.
        • Wu J.
        • Kerezsi E.H.
        • et al.
        Pregnancy-related relapses and breastfeeding in a contemporary multiple sclerosis cohort.
        Neurology. 2020; 94 ([Internet] Available from:): e1939-e1949
        • Leguy S.
        • Lefort M.
        • Lescot L.
        • Michaud A.
        • Vukusic S.
        • Le Page E.
        • et al.
        COPP-MS: corticosteroids during the Post-Partum in relapsing Multiple Sclerosis patients.
        J. Neurol. 2022; ([Internet]0123456789Available from:)https://doi.org/10.1007/s00415-022-11215-7
        • Leray E.
        • Moreau T.
        • Fromont A.
        • Edan G.
        Epidemiology of multiple sclerosis.
        Rev. Neurol. (Paris). 2016; 172 ([Internet] Available from:): 3-13
        • Martinelli V.
        • Colombo B.
        • Dalla Costa G.
        • Dalla Libera D.
        • Moiola L.
        • Falini A.
        • et al.
        Recurrent disease-activity rebound in a patient with multiple sclerosis after natalizumab discontinuations for pregnancy planning.
        Mult. Scler. 2016; 22 ([Internet] Available from:): 1506-1508
        • Nelson L.M.
        • Franklin G.M.
        • Jones M.C.
        Risk of multiple sclerosis exacerbation during pregnancy and breast-feeding.
        JAMA. 1988; 259 ([Internet] Available from:): 3441-3443
        • Nguyen A.L.
        • Havrdova E.K.
        • Horakova D.
        • Izquierdo G.
        • Kalincik T.
        • van der Walt A.
        • et al.
        Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: a contemporary cohort study.
        Mult. Scler. Relat. Disord. 2019; 28 ([Internet] Available from:): 235-243
        • Novi G.
        • Ghezzi A.
        • Pizzorno M.
        • Lapucci C.
        • Bandini F.
        • Annovazzi P.
        • et al.
        Dramatic rebounds of MS during pregnancy following fingolimod withdrawal.
        Neurol. Neuroimmunol. Neuroinflamm. 2017; 4 ([Internet]Nov 14Available from:): e377
        • Portaccio E.
        • Ghezzi A.
        • Hakiki B.
        • Martinelli V.
        • Moiola L.
        • Patti F.
        • et al.
        Breastfeeding is not related to postpartum relapses in multiple sclerosis.
        Neurology. 2011; 77 ([Internet] Available from:): 145-150
        • Portaccio E.
        • Ghezzi A.
        • Hakiki B.
        • Sturchio A.
        • Martinelli V.
        • Moiola L.
        • et al.
        Postpartum relapses increase the risk of disability progression in multiple sclerosis: the role of disease modifying drugs.
        J. Neurol. Neurosurg. Psychiatry. 2014; 85 ([Internet] Available from:): 845-850
        • Portaccio E.
        • Moiola L.
        • Martinelli V.
        • Annovazzi P.
        • Ghezzi A.
        • Zaffaroni M.
        • et al.
        Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: II: maternal risks.
        Neurology. 2018; 90 ([Internet] Available from:): e832-e839
        • Roullet E.
        • Verdier-Taillefer M.H.
        • Amarenco P.
        • Gharbi G.
        • Alperovitch A.
        • Marteau R.
        Pregnancy and multiple sclerosis: a longitudinal study of 125 remittent patients.
        J. Neurol. Neurosurg. Psychiatry. 1993; 56 ([Internet] Available from:): 1062-1065
        • Sempere A.P.
        • Berenguer-Ruiz L.
        • Feliu-Rey E.
        Rebound of disease activity during pregnancy after withdrawal of fingolimod.
        Eur. J. Neurol. 2013; 20 ([Internet] Available from:): e109-e110
        • Sepúlveda M.
        • Montejo C.
        • Llufriu S.
        • Sola-Valls N.
        • Reyes D.
        • Martinez-Lapiscina E.H.
        • et al.
        Rebound of multiple sclerosis activity after fingolimod withdrawal due to planning pregnancy: analysis of predisposing factors.
        Mult. Scler. Relat. Disord. 2020; 38 ([Internet] Available from:)101483
        • Thompson A.J.
        • Baranzini S.E.
        • Geurts J.
        • Hemmer B.
        • Ciccarelli O.
        Multiple sclerosis.
        Lancet (London, England). 2018; 391 ([Internet] Available from:): 1622-1636
        • Thompson A.J.
        • Banwell B.L.
        • Barkhof F.
        • Carroll W.M.
        • Coetzee T.
        • Comi G.
        • et al.
        Diagnosis of multiple sclerosis: revision of the McDonald criteria 2017.
        Lancet Neurol. 2018; 89: 1344-1354
        • Verhaeghe A.
        • Deryck O.M.
        • Vanopdenbosch L.J.
        Pseudotumoral rebound of multiple sclerosis in a pregnant patient after stopping natalizumab.
        Mult. Scler. Relat. Disord. 2014; 3 ([Internet] Available from:): 279-281
        • Vukusic S.
        • Michel L.
        • Leguy S.
        • Lebrun-Frenay C.
        Pregnancy with multiple sclerosis.
        Rev. Neurol. (Paris). 2020; ([Internet] Available from:)
        • Vukusic S.
        • Casey R.
        • Rollot F.
        • Brochet B.
        • Pelletier J.
        • Laplaud D.A.
        • et al.
        Observatoire Français de la Sclérose en Plaques (OFSEP): a unique multimodal nationwide MS registry in France.
        Mult. Scler. 2020; 26 ([Internet] Available from:): 118-122
        • Vukusic S.
        • Ionescu I.
        • Cornu C.
        • Bossard N.
        • Durand-Dubief F.
        • Cotton F.
        • et al.
        Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: the POPARTMUS study.
        Mult. Scler. 2020; ([Internet]1352458520978218Available from:)
        • Yeh W.Z.
        • Widyastuti P.A.
        • Van der Walt A.
        • Stankovich J.
        • Havrdova E.
        • Horakova D.
        • et al.
        Natalizumab, fingolimod, and dimethyl fumarate use and pregnancy-related relapse and disability in women with multiple sclerosis.
        Neurology. 2021; 96 ([Internet]Oct 22Available from:): e2989-e3002