Younger Age, DMT Use at Early Relapse May Lessen Later Disability

People with  multiple sclerosis (MS) who are using a disease-modifying therapy — and are at a younger age — when they have a relapse within the first three years of their disease course are more likely to recover completely, lowering their risk of long-term, 10-year disability, a study suggests.

Complete recovery may also be more likely in these patients if they have no bowel, bladder, or cognitive symptoms.

The study, “Relapse recovery in Multiple Sclerosis: Effect of Treatment and Contribution to Long-term Disability,” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.

Relapses, or unpredictable episodes of disease worsening, are a key feature of MS. Long-term outcomes for patients, including progression to severe disability, are mainly determined by the frequency and severity of their relapses and how well they recover.

The degree of recovery varies greatly among patients, with up to 59% of relapses resolving incompletely, i.e., with persistent nerve damage. Various disease-modifying treatments (DMTs), including interferons and steroids, are used to reduce relapse risk and severity and progression to disability.

Scientists have established that the degree of relapse recovery predicts long-term outcomes in patients. However, the factors determining complete or incomplete recovery, and the impact of incomplete recovery on disability progression are not clear.

A team led by researchers at Harvard Medical School in Boston investigated factors likely to determine incomplete relapse recovery in the first three years. They also studied how DMTs affect recovery, and the impact of incomplete recovery on disability outcomes 10 years laters.

Disability outcomes were measured through the expanded disability status scale (EDSS; the higher the score, the greater is a patient’s disability level) and timed 25-foot walk (a mobility and leg function performance test).

A total of 360 patients, all enrolled in the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB) study, were included in the analysis; of these, 89.2% were white and 73.6% female. On average, patients were 35.8 years old when they noticed their first symptoms, and they were diagnosed at an average age of 36.7.

Their mean annualized relapse rate was 0.35; on average, patients had about two relapses, one initial episode and another within the first three years of diagnosis.

Nearly half, 44.6%, of these relapses left a residual or persistent deficit after at least six months.

Results showed that patients experiencing relapses in the first three years post-diagnosis were more likely to recover completely if they were younger, had a lower body mass index (BMI, a measure of body fat) and longer disease duration, and were using a DMT, specifically interferons or glatiramer acetate (sold as Copaxone and also available as generic formulations) at the time of the relapse.

Specifically, 51.8% of relapses in untreated patients had an incomplete recovery, compared to 28.9% in patients receiving a DMT.

“The most common treatments in our cohort, interferons and glatiramer acetate, were associated with improved relapse recovery,” the researchers wrote.

Patients treated with steroids were also more likely to recover completely. The data “showed a beneficial effect of steroid treatment on recovery. Previous studies have shown either a lack of effect, or an inconsistent improvement,” the team wrote.

Importantly, patients with no bladder, bowel, or cognitive symptoms were also found to be more likely to recover completely.

Regarding the 10-year disability outcomes, researchers found that while incomplete recoveries within the first three years of relapse increased disability scores, complete recoveries lowered them.

In a model taking into account several complex factors (multivariable model), the 10-year EDSS score rose by 0.6 points for each incomplete recovery a patient experienced. Patients with incomplete recoveries also completed the 25-foot walk test at slower speeds, suggesting poorer mobility.

“Our results demonstrated that the number of early relapses with incomplete recovery is a significant predictor of a patient’s 10-year disability, as measured by both EDSS and timed 25-foot walk, two valid, clinically relevant tools,” the researchers wrote.

In line with three-year findings, 10-year disability results were worse in those at older ages (an EDSS score increase of 0.02 points for each addition year of age) and associated with a higher BMIs (though not significantly) at first symptoms.

“The increase in 10-year disability with every incomplete recovery in the first three years indicates that incomplete recoveries predispose to worse long-term outcomes, either due to accumulating disability or a common, aggressive pathophysiology,” the researchers wrote.

Relapse recovery in these analyses was not associated with sex, smoking history, family history of MS, race or relapse duration, the study noted.

Study limitations include its retrospective (past events) nature, the lack of diversity of the study sample (predominantly white and female), and the inability to assess recovery with more specialized tools, the team wrote.

Nonetheless, the researchers believe that these data provide evidence that relapse recovery at the earliest clinical stages predicts 10-year disability, and that early treatment with DMTs can improve recovery and prevent long-term disability.

“These findings could directly inform clinical decision making, clinical trial design and translational research,” they concluded. “The growing evidence on the association between recovery and long-term disability should inform clinical decision-making: patients with incomplete recovery may require closer follow-up and more aggressive treatment.”