How I treat multiple sclerosis

Fourteen. That’s the number of FDA-approved disease-modifying therapies, or DMTs, that are used to treat relapsing-remitting multiple sclerosis. At least that’s how many there are at the time of this blog entry. In our latest episode of BrainWaves, Dr. Christopher Perrone provides some insight into why one drug may be selected over the other, and the risks involved in treatment. It’s not a straightforward decision to choose on drug (or drug class, see below) over another. And it is critical to involve your patient in this complex decision-making process in order to ensure satisfaction and compliance with the treatment option.

PLATFORM THERAPIES

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Dr. Christopher Perrone.

  • Interferon beta-1a (Rebif® or Avonex®)
  • Peginterferon beta-1a (Plegridy®)
  • Interferon beta-1b (Betaseron® or Extavia®)
  • Glatiramer (Copaxone® or Glatopa™)

ORAL AGENTS

  • Fingolimod (Gilenya®)
  • Teriflunamide (Aubagio®)
  • Dimethyl fumarate (Tecfidera®)

INTRAVENOUS AGENTS

  • Natalizumab (Tysabri®)
  • Mitoxantrone (Novantrone®)
  • Alemtuzumab (Lemtrada®)
  • Daclizumab (Zinbryta™)
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Dr. Perrone in the recording studio.

The platform therapies are a good starting point for many patients with mild symptoms of relapsing-remitting multiple sclerosis (RRMS). These injectable therapies are immunomodulatory cytokines of the interferon-beta class which serve to inhibit the activity of helper T-cells that may be involved in multiple sclerosis. Unlike most of the other therapies for RRMS, the interferons may have the most favorable safety profile and have been the longest studied in these patients. They may be the oldest drugs, but that does not mean they are ineffective. Compared to placebo, patients on interferon therapies have a >30% lower risk of relapse, a significant drop in lesion volume, and delayed time to the development of disability.

For patients with severe disease, other therapies may have greater efficacy than the interferons. Many neurologists have turned to natalizumab in recent years–a once monthly intravenously administered antibody against integrin, a transmembrane protein involved in white blood cell migration into the central nervous system. Other, “more potent” therapies include fingolimod, alemtuzumab, and mitoxantrone.

While pregnancy may be “protective” in RRMS, some patients desire treatment with DMTs prior to delivery. Although no DMT is truly risk-free during pregnancy (or even following delivery), glatiramer may confer the lowest risk of gestational complications. While glatiramer may be equally effective in RRMS compared to interferons (REGARD trial), it is currently pregnancy category B. This means there has been no observed risk in animal studies of glatiramer, and human studies (if performed) have no obvious risk during the first trimester. After delivery, the risk of relapse appears to increase rapidly, so initiation or resumption of DMT may be important.

Daclizumab is the most recent FDA-approved pharmacotherapy for RRMS. It acts as a monoclonal antibody against the alpha subunit of the IL-2 receptor, and prevents inflammation in a way unique to the DMTs. Compared to the already effective platform therapies, daclizumab resulted in a 54% reduction in new lesions in the DECIDE trial. However, daclizumab was also associated with significantly greater risk of rash, infections, and liver injury when compared to interferons.

As a disclaimer, this blog entry was meant to provide the reader with a peer-reviewed educational resource on disease modifying therapy in RRMS. This blog and the episode referenced provide a brief overview of treatment options for RRMS (and not other forms of multiple sclerosis or the radiologically isolated syndrome), and they are not intended to be used to justify the treatment of RRMS patients.

 

[Jim Siegler]


The content in this episode was vetted and approved by Salim Chahin.

REFERENCES

Wingerchuk DM and Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clinic proceedings. 2014;89:225-40.

Torkildsen O, Myhr KM and Bo L. Disease-modifying treatments for multiple sclerosis – a review of approved medications. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2016;23 Suppl 1:18-27.

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