MS Progression Affected by Degree of Relapse Recovery and Timing of DMT Use, Study Says

Recovering well after a first relapse and starting a disease-modifying therapy (DMT) immediately afterward considerably increases the likelihood of slowing progression in multiple sclerosis (MS), a study suggests.

Its findings support relapse recovery as a critical factor for DMT initiation, and one that should be assessed routinely in MS clinical trials, researchers said.

The study, “Relapse recovery: The forgotten variable in multiple sclerosis clinical trials,” was published in the journal Neurology: Neuroimmunology & Neuroinflammation.

How well a person recovers from an MS relapse is known to affect long-term disease course, with partial recovery being associated with residual disability and earlier onset of progressive MS.

While the effectiveness of DMTs — treatments that reduce the activity and progression of a disease — is known to lessen over time with MS, the role of early relapse recovery in their effectiveness remains unclear.

“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,” the researchers wrote.

A team with the Mayo Clinic College of Medicine and Science in Minnesota and Biogen set out to clarify how the degree of recovery from an early relapse impacts the effectiveness of Biogen’s Avonex (interferon beta-1a), a DMT, in halting disease progression, and whether such recovery should define the moment of DMT initiation.

Researchers analyzed data from the Phase 3 CHAMPS  clinical trial testing Avonex in a group of people with clinically isolated syndrome (CIS) — which often precedes MS development — and its follow-up extension study called CHAMPIONS (NCT00179478).

CHAMPS involved 383 people (mean age of 33, range 18 to 50 years) who had just experienced a first MS attack, and had brain lesions consistent with MS. Participants were randomly assigned to either Avonex or a placebo for three years, at which point they could choose to enter the extension study where everyone was given Avonex for up to seven years.

In this way, researchers could evaluate potential associations between recovery from a first relapse, the time of Avonex initiation (immediately or after three years of placebo use), and disease progression.

The degree of relapse recovery was assessed using the Expanded Disability Status Scale (EDSS) — a method of quantifying MS disability, with higher scores indicating greater disability — at enrollment (within 28 days of a first relapse) and again after at least six months. Disease progression was also evaluated using EDSS scores.

Recovery was classified as “good” if the patient had a EDSS score of zero at enrollment and after six or more months, or if the patient had a EDSS score above zero at enrollment but whose score showed improvement equal to or better than the median of the group.

Of the 328 patients with EDSS data at enrollment, 175 had a good recovery (94 on immediate treatment, and 81 on delayed treatment), and 153 had a poor recovery (77 on immediate, and 76 on delayed treatment).

Results showed that people with a good recovery and immediate Avonex initiation were the most likely (about a 65% chance) to remain at a minimal disability level (EDSS score of less than 2.5) by age 45 — beyond which there is a greater likelihood of developing progressive MS.

In turn, about 80% of patients with a poor recovery and a delayed DMT use (placebo group) had EDSS scores higher than 2.5 when they reached 45, reflecting only a 20% chance of minimal disability by that age.

People with a good recovery but delayed Avonex initiation, and those with poor recovery but immediate DMT initiation had similar  chances — around 50% — of a benign disease course by age 45.

The data suggest that “delaying initiation of DMTs, especially after a poorly recovered relapse, further hampers the likelihood of remaining relatively disability-free by critical age 45 years,” the researchers wrote.

Active brain lesions at enrollment were also seen to affect long-term disability regardless of the degree of relapse recovery and timing of treatment initiation. This suggests that active brain lesions should also be considered in the classification of relapse recovery at enrollment in future clinical trials, the team noted.

These findings “raise awareness of the importance of relapse recovery as a predictive factor of long-term outcomes in MS,” the researchers concluded.

Studies evaluating other DMTs are necessary to confirm how the degree of relapse recovery and the timing of initial DMT use affect disease course, they added.