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Incomplete MS relapse recovery predicted greater long-term disability



– Failure to recover completely from early relapses in multiple sclerosis (MS) is significantly associated with higher long-term disability, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Incomplete recovery thus should be given more consideration when evaluating research and clinical practice outcomes, the study investigators cautioned.

“We found that the recovery from early relapses is an important predictor of future disability,” first author Marinos G. Sotiropoulos, MD, of the department of neurology, Brigham and Women’s Hospital, Boston, said in an interview. “It should be incorporated in future predictive models of disease severity and clinical trials, [and] it could be useful in clinical decision making as well.”

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

To investigate the effect of incomplete relapse recovery in the first 3 years of MS on rates of disability at 10 years, Dr. Sotiropoulos and colleagues evaluated data on 360 patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation in Multiple Sclerosis at Brigham and Women’s Hospital) study. CLIMB is a natural history study spanning 20 years, with more than 2,000 patients.

Patients were included if at least 8.5 years had passed since their first documented symptom, if they were at least 18 years at their first visit to the Partners MS Center, if that visit occurred within 1 year of their first symptom, and if they had a diagnosis of relapsing-remitting MS or secondary progressive MS.

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

A total of 403 early attacks from those 308 patients were included in the study. Half of the attacks (50.4%) were followed by incomplete recovery after 6 months, defined specifically as an increase in the Expanded Disability Status Scale (EDSS) scores from baseline to at least 6 months after the onset of the attack.

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

Patients’ recovery index, defined as the percentage of early attacks that recovered completely, was significantly associated with 10-year EDSS scores (P less than .001).

Patient age at first symptom was also a significant predictor of 10-year disability (P less than .004). Factors that were significantly associated with incomplete relapse recovery were the duration of time from first symptom (P less than .001) and moderate severity of the relapse (P = .029).

With the type of drug treatment likely representing an important factor in whether a patient has incomplete relapse recovery, the issue should be the subject of further research, Dr. 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 [that] 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.”

The findings suggest that “patients with incomplete early recovery might be considered for highly effective disease-modifying therapy,” added senior author Tanuja Chitnis, MD, also of the department of neurology at Brigham and Women’s Hospital. “We are now analyzing the biological mechanisms associated with relapse recovery.”

The authors of a recent study that echoes the importance of relapse recovery call it “the forgotten variable in multiple sclerosis clinical trials.” In that study, the researchers found an increased likelihood of a benign disease course among patients who received immediate disease-modifying therapy (DMT) initiation after failing to have a good recovery from an initial relapse (Neurol Neuroimmunol Neuroinflamm. 2019 Dec 17;7[2]).

“Some clinicians may choose to hold off DMTs because the patient may not have high disease activity levels,” Burcu Zeydan, MD, a coauthor of that study and an assistant professor of radiology in the Center of MS and Autoimmune Neurology at the Mayo Clinic, Rochester, Minn., said in an interview.

“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 National MS Society Nancy Davis Center Without Walls. Dr. Sotiropoulos has received research support from Mallinckrodt. Dr. Chitnis has served on advisory boards for Biogen, Novartis, and Sanofi-Genzyme, and she has received research support from the Department of Defense, National MS Society, Guthy-Jackson Charitable Foundation, Novartis, Octave, Serono, and Verily. Dr. Zeydan had no disclosures to report.

SOURCE: Sotiropoulos MG et al. ACTRIMS Forum 2020. Abstract LB 317.

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