Tackling Progression Independent of Relapse Activity

For much of the history of multiple sclerosis (MS) care, success has been measured by preventing relapses and new lesions. Precision medicine pushes that definition further. It asks clinicians to account for the full range of each patient’s disease biology, including the processes that standard monitoring may miss. As understanding of MS deepens, the field is confronting how much of disability accumulation happens quietly, and how far current tools remain from capturing it.

NeurologyLive®, in collaboration with Cleveland Clinic Neurological Institute, is taking on those questions in its Roundtable series Precision Medicine in Multiple Sclerosis: Advances & Unanswered Questions. The series features Robert Bermel, MD, director of Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research; Marisa McGinley, DO, staff neurologist at the Mellen Center; and Rebecca Cebull, CNP, certified nurse practitioner at the Mellen Center. Each episode tackles a different piece of the precision medicine puzzle, from biomarkers and imaging to genetics and beyond.

Episode 5 focuses on progression independent of relapse activity (PIRA). Bermel notes that PIRA is still identified retrospectively, often when a patient describes a gradual loss of function with no clear starting point. He calls for a biomarker that can flag at-risk patients early, before significant disability builds up. In the meantime, he says, more sensitive in-clinic measures such as the 25-foot walk, the 9-hole peg test, and the Symbol Digit Modalities Test help document progression over time. Cebull adds that comorbidities and events such as hospitalizations make it difficult to separate MS-driven decline from other causes.

McGinley explains that disease-modifying therapies remain essential for controlling the inflammatory component of MS. Uncertainty remains about whether they have any indirect effect on smoldering disease, which complicates decisions about stopping treatment. She and Bermel stress that managing comorbidities such as diabetes and weight is “highly actionable,” even if it isn’t glamorous. Cebull closes by describing how she counsels patients to control what they can, so they are as healthy as possible when emerging options such as Bruton tyrosine kinase inhibitors, stem cell therapy, or CAR T-cell therapy become available.