Induction-maintenance

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Barts-MS rose-tinted-odometer ★★★ 

By definition an immune reconstitution therapy (IRT) for MS is given as a short course, i.e. as a one-off treatment in the case of HSCT or intermittently as in the case of alemtuzumab or cladribine. IRTs are not given continuously and additional courses of the therapy are only given if there is a recurrence of inflammatory activity. IRTs have the ability to induce long-term remission and in some cases potentially a cure. 

Immune reconstitution simply refers to the restoring of a competent immune system after a cycle, or cycles, of depletion. Immune competence in the context of an IRT refers to the ability of the immune system to respond to infection, in particular, opportunistic infections, mount an antibody response to vaccines and to perform normal systemic tumour surveillance. 

Immune reconstitution has been best shown in the context of hematopoietic stem cell transplantation (HSCT).  In the case of an IRT, for example, alemtuzumab or cladribine, which are given as short courses breakthrough disease activity can be used as an indicator to retreat rather than to necessarily switch therapy. Therefore, there a rebaselining MRI should be delayed until after the final initial course of therapy, e.g. 2 years, or close enough to the time when a third, or subsequent course, can be administered 

A major concern in relation to the wide adoption of IRTs is the uncertainty about the duration of their effectiveness and the concern that disease activity may reoccur at a level below the clinical and MRI monitoring thresholds used in routine clinical practice. If disease activity does reoccur will it cause irreversible end-organ damage? In addition, some IRTs, in particular, alemtuzumab and HSCT, are associated with a high rate of secondary autoimmunity and rarely with early and severe rebound disease activity.  

One strategy we are exploring is to use an IRT as true induction therapy and then maintain the treatment effect with safer maintenance therapies. In the case of alemtuzumab and HSCT, certain maintenance therapies could potentially prevent secondary autoimmunity and early rebound disease activity. 

We are in the process of preparing a grant application to explore the safety of an induction-maintenance treatment. Would you be interested in helping by completing the following survey? 

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

6 comments

Leave a Reply to Emma Cancel reply

  • Gavin, you can’t get valuable info from the above survey. The chosen treatment would be dependent on disease severity. Absolutely on board with this research BTW… glad you are doing something in this area.

    • I disagree.

      The valuable information obtained will be the opinion of the informed patient (one who understands risk/benefit) on preference (or not) of highly effective treatment early on in disease.

      My hypothesis is that the answers will show that patients are much more willing (than their neurologists understand) to take an aggressive stance against MS early on.

      These IRT options also allow for drug free pregnancy, an option not available in my fertile days.. I was left nulliparous after several rounds of ‘off drug, attempt to conceive, beck on drug to slow MS’, repeat x 3…

      Young women have so many options when diagnosed today. To those of us who are older it is disheartening to see some disavowed effective treatments.

    • Me like many others in UK I presume, were told to go to the MS decisions webpage and “make a choice on which one you want”. Minutes after confirmation of being told you have a progressive, dehabilitating disease.
      So no, chosen treatment is not dependent on disease severity.

  • I received alemtuzumab 2011 &2012 as first line therapy immediately following rapid diagnosis of what was looking like very aggressive ms – completely numb from chest down on first attack. Since 2013 I have been using copaxone as “belt and braces” on advice from neuro.
    I experienced ITP late 2018 – haematologist thought this had been triggered by flu vaccine, apparently not unheard of, neuro thought it was more likely to be alemtuzumab despite being almost 7 years after last dose.
    I do wonder if I am wasting both time and valuable NHS cash continuing with the copaxone after receiving alemtuzumab, but to be honest, am too afraid to stop.
    I have had one “tiny” relapse since diagnosis, new neuro did offer to change medication but could not advise long term effects so decided to stick with original plan.

  • I would go for IRT right now.
    In France, they just give you a first line therapy (aubagio, or IFNs) and then, only if they see the relapses at MRI (do not care about disability worsening) they go for Tysabri and Gilenya. Then, third line Ovrecus/Mitoxandrone/Endoxan.
    Unfortunately, Lemtrada and Mavenclad have been no accepted for reimbursement.
    HSCT is performed at fourth line for very limited cases (3 cases in 2019)
    So, limited disability = low effective therapy and so on… until EDSS 6 where they propose you endoxan or ocrevus. So, a conservative approach who do not take into consideration the objective of NEDA which should be now the policy for each patient…

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