Infusible Disease-Modifying Therapies For MS: Finding The Balance

By Kate Johnson


From the multiple sclerosis specialist working in a dedicated MS center, to the rural clinician with the occasional MS patient, there is little debate that infusible disease-modifying therapies (DMTs) have transformed care for this patient population. Natalizumab (Tysabri), ocrelizumab (Ocrevus), and alemtuzumab (Lemtrada), are all infusible monoclonal antibodies that have stormed the MS scene because of their efficacy and targeted effect, compared with older injectable DMTs such as beta interferons and glatiramer acetate. But while these newer therapies are considered by many to be preferable for prevention of clinical relapses and new MRI-detected lesions, they may not always be the ideal choice.

The hope in MS is to find the right drug for the right patient at the right time in the MS disease process. Unfortunately, we are not there yet.

“It all starts with patient preference,” said Lori Mayer, DNP, NP-C, MSN, RN, MSCN, who is the assistant medical director at Elligo Health Research in Austin, Texas. “I wish we had a test to tell us that this particular drug with this mechanism of action would work on this patient, but we don’t, so we have to look at the efficacy and safety, but also other things like a patient’s adherence, risk tolerance profile, and age. The hope in MS is to find the right drug for the right patient at the right time in the MS disease process. Unfortunately, we are not there yet.”

Selection of appropriate therapy for an individual patient depends on an honest discussion with the individual about the risk and benefits of a treatment along with the potential side effects and the burden to the patient of treatment, said Dr. Mayer. “Treatment choice is an informed joint decision.”



Dr. Lori Mayer

Respecting patient preference is among the first recommendations in the American Academy of Neurology’s practice guideline on MS DMTs (Neurology. 2018 Apr 24. doi:10.1212/WNL.0000000000005347) but physician preference is also an important consideration. Offering an infusible DMT is no simple undertaking, given the long list of possible drug- and infusion-related adverse effects, as well as the need for regular MRI monitoring to track efficacy and breakthrough disease activity.

“Most regional neurologists don’t offer infusion services within their practices. It would be difficult and expensive to set up: You need equipment, certified infusion professionals, staff, and standard operating procedures in place,” said Dr. Mayer. “I see regionally some of them are still using the platform therapies – interferons and glatiramer acetate – and even some of the oral therapies because it’s easier and they don’t have to do as much monitoring.”

For clinicians who aren’t comfortable with infusion therapy, but who feel it’s the best choice for the patient, off-site infusion facilities or referral to a specialized MS center are options. “Most MS clinics go straight to the higher-efficacy therapies because they’re more comfortable with them,” said Dr. Mayer. “Some patients will go to their MS clinic once a year and otherwise go to their regular neurologist with off-site infusion and monitoring. We work with a lot of patients who do that.”

In the absence of a definitive treatment algorithm for newer DMTs and the increasing choice of therapies available, MS practitioners face a complicated choice. While all three infusible DMTs are approved by the Food and Drug Administration for relapsing forms of MS, none are approved during pregnancy, so birth control should be part of the discussion if these therapies are chosen, she said.

Additionally, alemtuzumab, an immunosuppressive agent, can trigger infusion reactions, secondary autoimmunity, infections, neoplasms, and even arterial dissection and stroke, according to Robert H. Gross, MD and John R. Corboy, MD, in a recent review (Continuum [Minneap Minn]. 2019 Jun;25[3]:715-35). Its use “should be restricted to highly active MS under the supervision of providers with a high degree of familiarity and expertise with these medications.”

Fortunately, there is a range of therapies, each having its own efficacy and safety profile.

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In addition to regular monitoring for drug-related adverse events, detection and treatment of infusion-related reactions is an important aspect of any infusion therapy provider, said Dr. Mayer. These reactions, such as anaphylaxis or hypersensitivities, can appear either in the infusion suite or any time within the following 48 hours.

“There are numerous infusion reactions, and each product insert will tell you what could occur,” she said. “Each individual facility has their own standard of practices – it’s really up to each infusion service to have a specific protocol for their nurses to follow.”

Another uncomfortable reality that influences DMT drug choice is patient insurance. “There are some hoops,” acknowledged Dr. Mayer. For those patients whose insurance will not cover infusible drugs there are options, such as referring them to a university medical center where they may be eligible for clinical trial participation. “Pharmaceutical companies also have programs for free drugs,” she added. “But even with free drug, insurance may not cover all the costs of care. Understanding the economic risk is also important. The MS provider and the health care insurers themselves are a good source of information. In those patients who do not have insurance, several resources can facilitate finding affordable coverage important for this chronic disease.”