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STUDY: Treating aggressive MS

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  • STUDY: Treating aggressive MS

    Aggressive multiple sclerosis: Treatment

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    Georgina Arrambide, Ellen Iacobaeus, Maria Pia Amato, ...
    First Published June 12, 2020


    The natural history of multiple sclerosis (MS) is highly heterogeneous. A subgroup of patients has what might be termed aggressive MS. These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability at the earlier stages of the disease. Their therapeutic window of opportunity may be narrow, and while it is generally considered that they will benefit from starting early with a highly efficacious treatment, a unified definition of aggressive MS does not exist and data on its treatment are largely lacking. Based on discussions at an international focused workshop sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), we review our current knowledge about treatment of individuals with aggressive MS. We analyse the available evidence, identify gaps in knowledge and suggest future research needed to fill those gaps. A companion paper details the difficulties in developing a consensus about what defines aggressive MS.

    Dave Bexfield

  • #2
    Great study. I don’t think there is enough info on occurrence of aggressive MS and treatment options. Thanks for posting it Dave. Like you, I had an initial very aggressive disease course. I think a Rapid neurological decline is just as shocking to experience as it is to be the doctor in charge of slowing it. Interestingly, The article said there was a lack of consensus of what defines aggressive. It seems one recognizes it when you see it. But I think many are caught flat footed when it’s onset can be so sudden. I like that The article lists various treatment options from copaxone to stem transplant, and details which options provided best slowing and even allowed some patients to recover ability. There is also a bit about treating an aggressive course during pregnancy. i believe DMTs are. not fully utilized by neuros for fear of harming baby, so I think it is worth quoting:

    Pregnancy risks should be discussed with patients and spouses before starting any DMT.55Information on treatment of patients with highly active MS during pregnancy is limited. Most data come from studies and observations on individuals with a broad spectrum of MS phenotypes and severities. Therapies which can be administered throughout pregnancy or those which are stopped at conception but have lasting effects throughout pregnancy should be considered.

    Immune reconstitution treatments administered in short courses, such as alemtuzumab, cladribine and probably rituximab, offer a window of opportunity in patients with aggressive MS planning a pregnancy (typically 4–6 months after the last dose, with some authors suggesting 1 month in the case of rituximab).5659 To minimize the risk of recurrent disease activity in patients stable while using natalizumab, continuing treatment until the beginning of the third trimester or throughout pregnancy should be considered, as the haematological changes reported in exposed newborns are temporary and not clinically relevant.55,60 In the rare occurrence of aggressive MS developing in a pregnant woman, natalizumab or anti-CD20 therapies might be considered, but evidence of their safety and efficacy in such a situation is scant. This is an area for future research. Fingolimod is contraindicated not only due to the risk of recurrent disease activity after stopping treatment, but mainly due to the increased risk of major birth defects in exposed infants.61

    After delivery, early reintroduction of DMTs is advisable if prior therapies do not have long-lasting therapeutic effects.62,63 In case of relapses, PLEX has been used successfully during pregnancy,64 but caution should be used since it can aggravate IRIS-like phenomena following natalizumab discontinuation.65,66 There is no specific evidence supporting the use of IA or IVIg as alternatives to PLEX in pregnant women with highly active MS.
    55. Dobson, R, Dassan, P, Roberts, M, et al. UK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines. Pract Neurol 2019; 19(2): 106–114.
    Google Scholar | Crossref | Medline

    61. EMA . Updated restrictions for Gilenya: Multiple sclerosis medicine not to be used in pregnancy, (2019, accessed 25 November 2019).
    Google Scholar
    62. Vukusic, S, Durand-Dubief, F, Benoit, A, et al. Natalizumab for the prevention of post-partum relapses in women with multiple sclerosis. Mult Scler 2015; 21(7): 953–955.
    Google Scholar | SAGE Journals | ISI
    63. Portaccio, E, Moiola, L, Martinelli, V, et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: II: Maternal risks. Neurology 2018; 90(10): e832–e839.
    Google Scholar | Crossref | Medline
    64. Cox, JL, Koepsell, SA, Shunkwiler, SM. Therapeutic plasma exchange and pregnancy: A case report and guidelines for performing plasma exchange in a pregnant patient. J Clin Apher 2017; 32(3): 191–195.
    Google Scholar | Crossref | Medline
    65. Lenhard, T, Biller, A, Mueller, W, et al. Immune reconstitution inflammatory syndrome after withdrawal of natalizumab? Neurology 2010; 75(9): 831–833.
    Google Scholar | Crossref | Medline

    To anyone out there pregnant or knows someone that is pregnant with onset of an aggressive MS course, there is hope. I was treated with iv steroids during pregnancy and helped slow a severe attack, and there were no ill effects to my baby. My OB worked closely with neurologist and I was assured a large percentage of steroids was filtered by placenta. I choose to breastfeed for first week to give my baby the benefits of antibodies etc from breastmilk and to go on dmd after first week postpartum and stop breastfeeding. There are more studies today that can better inform you about safety of DMTs and breastfeeding.