Early High-Efficacy Therapy in MS: Escalation, De-Escalation, and Ongoing Trials

This episode, "Early High-Efficacy Therapy in MS: Escalation, De-Escalation, and Ongoing Trials," features Drs. Longbrake and Newsome describing how their own practices have evolved.

Dr. Nair asks whether the treatment paradigm has shifted, given the continuum view of MS and more than 20 available therapies. Dr. Longbrake answers yes. Every MS therapy has responders and non-responders, but clinicians cannot identify them up front, and each relapse or breakthrough costs ground.

She estimates that clinicians can be roughly 95 percent sure of a response to a high-efficacy anti-CD20 therapy, which is far more likely than with a drug such as teriflunomide. Treating MS biology early produces better long-term outcomes, and observational data suggest nothing is gained by holding high-efficacy therapy in reserve. She now uses it early and is deciding how and when to de-escalate as patients age.

Dr. Newsome agrees that aggregate data favor high-efficacy drugs for relapsing biology. The major stumbling block is whether a young patient can remain on B-cell depletion for decades, since longer-term infections have appeared. How long to treat aggressively remains unclear, and some clinicians use extended-interval dosing.

He highlights two randomized trials in early relapsing MS. TREAT-MS, led by his group, uses EDSS Plus as its primary outcome and reaches data lock next month with about 900 patients. DELIVER-MS, led by Cleveland Clinic, has brain atrophy as its primary outcome and enrolled 800. They may identify who needs high-efficacy therapy immediately and who can escalate safely.

Dr. Newsome stresses shared decision-making. Some patients never start a drug after agreeing to it, and some will not accept any risk of a deadly brain infection. For those who choose a less effective option, he recommends closer follow-up and clear guidance on when to return.

Our next episode, "Individualizing MS Treatment: Risk Stratification, Biomarkers, and Patient Preference," turns to biomarkers, baseline immune testing, and a proposed risk score for individualized decisions.