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4yr
Multiple Sclerosis and Monoclonal Antibodies

MS damages the brain from the start of the disease and clinicians are challenged to treat the disease early before irreparable damage to the brain and its limited mechanisms for repair are damaged. There is consensus on the importance of early intervention to maximize lifelong brain health.1 Cognitive health is impaired before walking ability, and cognitive deficit, not walking ability, has the biggest impact on employment in people with MS.2  Survey respondents from both the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry and the American Academy of Neurology MS Disease Modifying Treatment (DMT) guideline development panel cited the “selection of therapies most likely to lead to improvements in quality-of-life measures, MS symptoms, and preservation of cognition" as top priorities in DMT selection.3

Monoclonal antibody (mAb) therapies have become one of the preferred treatments for relapsing and progressive forms of MS as they target specific mechanisms of the disease. Clinically, their use can be found as “induction” agents or later as “escalation” therapies after patients fail less efficacious drugs. FDA approved agents, alemtuzumab, natalizumab, ocrelizumab, and ofatumumab are each proven to be safe, highly therapeutic agents with unique benefits and risks. Delivery of these treatments is either intravenous or subcutaneous, and varies from monthly, every six months, or annual cycles. Patients self-administer or attend infusion centers with varying delivery times based upon the drug received.

Given the importance of maximizing brain health, what is your approach to treating MS early?

How do you and your patients weigh quality-of-life, symptom improvement, and preservation of cognition in determining the best course of treatment for them? 

  1. Giovannoni, G, Butzkueven H, Dib-Jalbut S, et al Brain Health: time matters in multiple sclerosis. UK: Oxford PharmaGenesis, 2015. Google Scholar
  2. Strober L, Ciaravalloti N, Moore N, et al Unemployment in multiple sclerosis (MS); utility of the MS Functional Composite and cognitive testing. Mult Scler 2014; 20:112-5. Doi: 10.1177/1352458513488235 CrossRefPubMed Google Scholar
  3. Gregory S. Day, Alexander Rae-Grant, Melissa J. Armstrong, et al. Identifying priority outcomes that influence selection of disease-modifying therapies in MS. Neurol Clin Pract published online April 23, 2018. DOI 10.1212/CPJ.0000000000000449
  4. Elsbernd PM, Carter JL. Using Monoclonal Antibody Therapies for Multiple Sclerosis: A Review. Biologics. 2021; 15:255-263. https://doi.org/10.2147/BTT.S267273
  • 4yr
    I also agree with Dr Friend. Risk versus benefit analysis becomes more important the more side effects anticipated. Carefully weighing the options is crucial.
  • 4yr
    The optimal choice of first line DMT is always a clinical and shared decision. I agree with Dr. Chauhan that using induction therapy with highly effective DMTs to treat MS early and aggressively may have therapeutic impact on improving patient quality of life and preserving brain health and cognitive function.

    In my experience, monoclonal antibodies, in particular Ocrelizuma and Ofatumumab, are well received and appreciated by MS patients, their caregivers and treating physicians, due to their proven high efficacy, safety and convenient dosing regimen.

    Two recent studies, from UK and from a global study including the MSBase Registry, comparing MS patients given early high-efficacy versus escalation therapy, also support highly effective monoclonal antibodies.
  • 4yr
    I agree with my Fellow Neurologist about worrying about side effects. However , we do no have crystal ball which MS patient will be wheel chair bound and who will be walking in in 5 to 10 yrs in their disease process. Once they have severe MS symptoms or severe relapse or secondary progression or worsening of MRI findings including Spinal cord lesion-- It may be too late for effectiveness of Monoclonal antibody /Infusion therapy to have same success as Early in diseases process.
    When physician are worried about side effects of Monoclonal antibody, patient will not get same benefit of all available options. The neurologist should work with Model of SDM (Shared Decision Making) concept. We should offer best available option to the patient and of course discuss risk and benefit of all available therapy . Once patient EDSS is more than 5 or with cognitive impairment or severe lesion burden on mri brain and spine: Considering Monoclonal antibody/infusion therapy may not be right time or enough to hold diseases progression.
    We all have seen severe end stage MS patient and it is very sad that we cannot offer them to bring their life back or improve quality of life. If AAN or CMSC or European MS society come with guideline regarding Induction therapy and Maintenance therapy guidelines - it will help global MS care. I wish we can learn from Rheumatologist how they are treating RA in last 10 yrs.
  • 4yr
    I actually don't believe the hit hard with the highest efficacy agent in MS first. You are risking more side effects. I agree with monoclonal antibodies being generally safe, however they are not safer than orals or platform therapies. I think you are doing a patient a disservice by starting with a monoclonal antibody if they don't have risk factors for a severe MS course. how would you feel if a patient with mild optic neuritis, barely meets criteria on MS with one enhancing lesion and 2-3 other white matter lesions, age 55 and Caucasian, no other lesions, and then you give ocrevus and she gets breast cancer? this patient likely would have done well even with platform therapy, yet you risked breast cancer blindly believe that monoclonal antibody treatment should be used to hit the disease hard first. treatments should be tailored to the patient.
  • 4yr
    It is exciting time in management of RRMS AND SPMS. It is very sad that all health care provider involved in MS management are not on same page and patient does not get advantage of all available effective options. We have multiple scale , imaging marker, biomarker to measure diseases activity and progression. We have not focussed on cognitive function in the past , however monitoring and maintaining cognitive function is priority in MS management.

    Early aggressive treatment/DMD (Induction) therapy with highly effective infusion is important step Early in diseases course. Once disease is advance , infusion therapy may not have same level of success in control of diseases activity.

    Success of treatment is measure based on improving patient quality of life , maintaining physical or improving physical and cognitive function.

    Aggressive infusion therapy options should be available and offer to all MS patient .
    We have to discuss risk of side effects (monitoring side effects) and Benefit of controlling diseases activity is priority .

    I wish all MS patient have all option available no matter where they get their MS care.

  • 4yr
    I agree with Dr Friend. Using DMT’s in patients that might not benefit, e.g. Inactive SPMS patients is in fact dangerous as per the risk/benefit ratio. So the key is accurate diagnosis, and my beef is that the Pharm companies thru MS societies have tried to restrict modalities for quantifying MS based on brain imaging, removing select parameters for measurement of brain volume (especially grey matter volume) and look for apoptotic death of neurons within grey matter as a mechanism for cognitive change. Or looking at selective PET ligands to asd additional information. I could be wrong but personally that is my concern
  • 4yr
    For relapsing and progressive forms of MS preservation of brain function mobility and cognition are the priorities. However, we have to be aware of the potential risk factors that may limit the use of some of these medications.

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