Identifying Optimal Candidates for Early Intervention of Dimethyl Fumarate: Darin Okuda, MD, FAAN, FANA

"We don’t know how a person would have been in life had changes been suppressed. We know there’s very obvious changes in multiple sclerosis punctuated by these bright, large, white T2 hyperintense lesions within the brain and spinal cord. But there’s also occult changes that are below the resolution of MRI. What if a treatment worked to address the occult changes?"

Radiologically isolated syndrome (RIS) refers to a clinical situation in which an individual has white matter lesions suggestive of multiple sclerosis (MS), as shown on an MRI scan that was done for reasons unrelated to MS symptoms. The 2 conditions have been interlinked since RIS was first introduced in 2009; however, being diagnosed with RIS does not directly correlate with a diagnosis of MS. Over time, culminating research has suggested that early intervention of disease-modifying therapies for MS may result in greater long-term outcomes, including reduced risk of relapse.

Similarly, those in the MS community have floated the idea that effectively treating RIS at its earliest stages may lead to reduced risk of first clinical demyelinating event. Led by Darin Okuda, MD, FAAN, FANA, the recently published ARISE study (NCT02739542) was the first to show a disease-modifying effect in patients with RIS. In a cohort of 87 patients who met the 2009 RIS criteria, findings showed that treatment with dimethyl fumarate (Tecfidera; Biogen) significantly lowered the risk of first event by 82% during a 96-week treatment period (hazard ratio, 0.18; 95% CI, 0.05-0.63; P = .007). Additionally, 33% of patients on placebo and 7% on active drug demonstrated a first acute neurological symptom associated with central nervous system demyelination after 96 weeks.

These results are the first of its kind and serve as an important step for patients with RIS; however, more work is needed to be done, noted Okuda. In an interview with NeurologyLive®, Okuda, director of Neuroinnovation and Multiple Sclerosis & Neuroimmunology Imaging Program at UT Southwestern Medical Center, provided insight as to whether certain patients may be better candidates for this therapy. He stressed that while these data serve as preliminary evidence for this effect, understanding and identifying patients with RIS remains a challenge the clinical community is working towards.