Incomplete MS Relapse Recovery Predicts Long-Term Disability

Nancy A. Melville

March 03, 2020

WEST PALM BEACH, Florida — The failure to have a complete recovery from early relapses in multiple sclerosis (MS) is significantly associated with higher long-term disability and should be given more consideration when evaluating outcomes both in research and clinical practice, a new study suggests.

"We found that the recovery from early relapses is an important predictor of future disability and it should be incorporated in future predictive models of disease severity and clinical trials, while it could be useful in clinical decision-making as well," first author Marinos G. Sotiropoulos, MD, of the Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News.

Their findings were presented here at the fifth annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020.

Incomplete recovery from relapses is known to be linked to disability progression and the likelihood of transitioning to secondary progressive MS, however, research on its role in longer-term outcomes is lacking.

To investigate the effect of incomplete relapse recovery in the first 3 years of MS on rates of disability at 10 years, Sotiropoulos and colleagues evaluated data on 360 patients enrolled in the Comprehensive Longitudinal Investigation in Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) study, a natural history study spanning 20 years, with more than 2000 patients.

Patients were included if at least 8.5 years had passed since their first documented symptom, their first visit to the Partners MS Center occurred within 1 year of their first symptom, and they had a diagnosis of relapsing-remitting or secondary progressive MS.

Among the 308 patients included in the study, 74% were women and 89% white, with a mean age at the first symptom of 35.9 years.

A total of 403 early attacks experienced by patients were included in the study. Of these, 50.4% had an incomplete recovery after 6 months, defined specifically as an increase in the Expanded Disability Status Scale (EDSS) score from baseline to at least 6 months after onset of the attack.

As of their 10-year visit, 27.3% of patients had a normal examination, defined as an EDSS 0, and 64.1% had no significant disability (EDSS < 2). The mean EDSS at 10 years was 1.52.

The study results showed that patients' recovery index, defined as the percentage of early attacks that recovered completely, was significantly associated with 10-year EDSS scores (P < .001).

Patient age at first symptom was also a significant predictor of 10-year disability (P < .004).

Factors that were significantly associated with incomplete relapse recovery were duration of time from first symptom (P < .001) and moderate severity of the relapse (P = .029).

Because the type of drug treatment is likely an important factor as to whether or not a patient has incomplete relapse recovery, the issue should be the subject of further research, Sotiropoulos said.

"This is something that is important to look at because none of the clinical trials for the drugs we currently have looked at relapse recovery as an outcome," he explained.

"There have been some post-hoc analyses which have shown that some of the new medications can improve recovery from relapses, but there is a lot to look into now that we know relapse recovery is an important clinical parameter," he said. "We have to factor in the treatment effect in preventing residual disability after relapses."

Senior author Tanuja Chitnis, MD, also of the Department of Neurology, Brigham and Women's Hospital, added that the findings suggest "patients with incomplete early recovery might be considered for highly effective disease-modifying therapy."

"We are now analyzing the biological mechanisms associated with relapse recovery," she told Medscape Medical News.

Another recent study that echoes the importance of relapse recovery calls it "the forgotten variable in multiple sclerosis clinical trials."

In that report, researchers found an increased likelihood of a benign disease course among patients who received immediate disease-modifying therapy initiation after failing to have a good recovery from an initial relapse.

"Some clinicians may choose to hold off disease-modifying therapies because the patient may not have high disease activity levels," Burcu Zeydan, MD, a coauthor of that study and assistant professor of radiology in the Center of Multiple Sclerosis and Autoimmune Neurology, at the Mayo Clinic, in Rochester, Minnesota, told Medscape Medical News.

"What these studies add is that if a patient is a poor recoverer despite not having highly active disease, that patient should be considered for immediate treatment initiation," she said.

"Otherwise, there is the possibility of a next relapse, which may not happen often, but when it happens, it may lead to more residual deficit with additional disability burden."

The CLIMB study received funding from Mallinckrodt and the Nancy Davis Center Without Walls, National Multiple Sclerosis Society. Sotiropoulos has reported receiving research support from Mallinckrodt. Chitnis has reported serving on advisory boards for Biogen, Novartis, and Sanofi-Genzyme, and has received research support from the Department of Defense, National Multiple Sclerosis Society, Guthy-Jackson Charitable Foundation, Novartis, Octave, Serono, and Verily. Zeydan has reported no relevant financial relationships.

ACTRIMS Forum 2020. Poster LB317. Presented February 28, 2020.

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