Immediate Disease-Modifying Therapy After Relapse Reduces MS Disability

Patients with multiple sclerosis (MS) without good recovery after initial relapse, who receive immediate disease-modifying therapy (DMT) initiation, have an increased likelihood of a benign disease course, according to research.

The study, published by Neurology’s Neuroimmunology & Neuroinflammation, involved a double-blind, placebo-controlled trial of interferon beta-1a 30 mc once a week in clinically isolated syndrome and a 10-year follow-up extension trial.

The researchers defined good recovery after presenting relapse as:

1. Full early recovery within 28 days of symptom onset, meaning an Expanded Disability Status Scale (EDSS) score of 0 at enrollment and maintained for at least 6 months.
2. Delayed good recovery with an EDSS score of above 0 at enrollment and improvement from peak deficit to 6^th month or 1-year visit that is greater than or equal to the median.

“In multiple sclerosis (MS), partial recovery from relapses leads to residual disability. Limited recovery from early clinical relapses also situates patients with MS for an earlier onset of progressive disease. A single, partially recovered, symptomatic or asymptomatic, critically located lesion in the high cervical spinal cord is sufficient to set a patient up for progressive disease,” the authors said. “A common real-world practice in deciding immediate vs delayed DMT initiation in early MS often involves the extent and rapidity of a patient’s recovery from early relapses, a decision for which there is no evidence from a clinical trial setting.

In total, 175 of 328 patients had good recovery—94 immediate and 81 delayed treatment—while 153 did not have good recovery (77 immediate and 76 delayed treatment). According to the results, patients with good recovery and immediate initiation of DMT after their first relapse have ~65% chance of remaining at a minimal disability level by age 45. However, patients with poor recovery and delayed DMT initiation have ~20% chance of remaining at a minimal disability level of EDSS score of less than 2.5 by age 45. Additionally, those with poor recovery but immediate DMT initiation or patients with good recovery but delayed DMT initiation have ~50% chance of remaining at a disability level of EDSS score less than 2.5 by age 45.

The results suggest that delaying initiation of DMTs, especially after a poorly recovered relapse, decreases the likelihood of remaining disability free by age 45.

“A better understanding of the biology underlying relapse recovery in MS is of utmost importance in generating better animal models of recovery, in developing better recovery agents, in more optimal timing of administration of recovery agents in future recovery trials, and in defining the clinical/ subclinical metrics appropriate for the recovery measurement,” the authors concluded. “It is very likely that DMTs and medications stimulating relapse recovery will be used concomitantly, and clinical or subclinical metrics that can assess such interactions will be further relevant in future clinical trials.”

Reference

Kantarci OH, Zeydan B, Atkinson EJ, et al. Relapse recovery: The forgotten variable in multiple sclerosis clinical trials [published online December 17, 2019]. Neurology Neuroimmunology & Neuroinflammation. doi: https://doi.org/10.1212/NXI.0000000000000653.