Induce or Escalate? Hopkins Neurologist Mowry Addresses Treatment Strategy Debate in Multiple Sclerosis

In keeping with a true “hybrid” meeting format, some CMSC speakers presented using video technology. Ellen Mowry, MD, of Johns Hopkins Medicine, delivered her Presidential Lecture from her home base in the Baltimore area.ORLANDO, Fla. – More therapies, more choices. What strategy should clinicians follow to ensure the best outcomes for their patients with multiple sclerosis (MS)? In her Presidential Lecture here on Tuesday, October 26, Ellen Mowry, MD, described available research supporting the decision of whether to use an escalation or induction approach to disease-modifying therapy (DMT), given the large variety of agents available.

“Those of us who treat MS are aware that there's a great push to consider starting with a higher-efficacy therapy at onset,” said Dr. Mowry, Professor of Neurology and Director of the Multiple Sclerosis Experimental Therapeutics Program at Johns Hopkins Medicine in Baltimore, MD. When making this decision, she asks herself: What are we actually trying to do when treating a person with MS? “There are very few patients these days who do not achieve control of their inflammatory activity—the relapses and lesions on MRI—at least in my clinic,” she said. “I am really interested in understanding whether the treatment choice made at the time of diagnosis can make a difference in how the patient is doing several years down the road. Can I adjust the way I practice to prevent sustained disability over time? And to do this, do I need to start with a higher efficacy DMT?” She noted that, for most patients, she starts with a moderate efficacy agent and monitors treatment response carefully, unless the patient presents with indicators of aggressive disease or poor prognosis.

Elbow-bumps only. Safety precautions against COVID-19 were not an afterthought, but were actively encouraged at the 2021 CMSC Annual Meeting.Data comparing individual agents and classes of DMTs should be interpreted with caution, Dr. Mowry noted. Efficacy and effectiveness are not the same thing. Efficacy is how an intervention works in the context of large clinical trials, while effectiveness means how medications work in the real world. “When looking at efficacy, we're usually talking about how well that medication performed at reducing relapse rates in MS clinical trials.” These trials average a therapy’s impact across the groups assigned to those therapies. They usually exclude a large number of patients who don’t fit the study criteria. In contrast, MS patients in the “real world” have more comorbidities, inconsistent adherence, and many other treatment variables. These may include long waits in starting or switching treatments due to delayed insurance authorization. Observational studies also have limitations, Dr. Mowry noted. Patients are not always taking the best therapy for them, but may be on the therapy that their medical plan will pay for.

Dr. Mowry is currently involved with two trials sponsored by the Patient Centered Outcomes Research Institute (PCORI) designed to help resolve the escalate versus induction debate. TREAT-MS has enrolled 600 of the targeted 900 patients at more than 45 sites nationwide (both academic and private practices). The goals are to evaluate:

• Does an “early aggressive” therapy approach, versus starting with a traditional therapy, influence the intermediate-term risk of disability progression? These findings will be stratified according to whether the patient was at high or low risk for long-term disability.
• Among “low risk” patients who started on first-line MS therapies and experienced breakthrough disease, is their risk of disability progression different if they were switched to a higher-efficacy therapy versus a different first-line therapy?

DELIVER MS is another PCORI study, this one designed to look at differences in brain volume changes when comparing an early high-efficacy therapy to a standard escalation approach. Dr. Mowry encouraged CMSC attendees to learn more about the studies and to consider enrolling eligible patients.