Fingolimod improves cerebral hemorrhage outcomes in pilot study

By Anne Harding

NEW YORK (Reuters Health) - The multiple sclerosis (MS) drug fingolimod has shown promise for treating intracerebral hemorrhage (ICH) in a new proof-of-concept study.

Patients given the sphingosine 1-phosphate receptor (S1PR) modulator within 72 hours had reduced perihematomal edema (PHE), fewer neurologic deficits and a faster recovery than those who did not receive the drug, Dr. Fu-Dong Shi of Tianjin Neurological Institute at Tianjin Medical University General Hospital in China and colleagues found.

"The efficacy of fingolimod in preventing secondary brain injury in patients with ICH warrants further investigation in late-phase trials," Dr. Shi and colleagues conclude in their report, published online July 7 in JAMA Neurology.

Given that much of the damage with hemorrhagic stroke is due to edema and inflammation, and that fingolimod blocks the release of lymphocytes from lymph nodes and can penetrate the blood-brain barrier, the investigators hypothesized that the drug could reduce PHE and improve outcomes in patients with ICH.

To investigate, they enrolled 23 patients with supratentorial ICH of 5 to 30 mL and a Glasgow Coma Scale (GCS) score of 6 or higher in a case-control clinical trial. Twelve patients received standard management, including antihypertensives and nimodipine, and 11 received standard management plus fingolimod 0.5 mg orally once a day for three consecutive days.

At baseline, 42% of control patients had a GCS score of 15, as did 18% of the fingolimod group. At seven days, half the control group - and everyone in the fingolimod group - had GCS scores of 15.

National Institutes of Health Stroke Scale scores were reduced by 0.5 in the control patients at day 7, versus 7.5 for the fingolimod group. Dr. Shi and colleagues also observed a reduction in circulating lymphocyte counts among the patients on fingolimod.

By three months, 63% of the fingolimod-treated patients - but none in the control group - had full recovery of neurologic function. Patients treated with fingolimod also had significantly smaller PHE volume and fewer ICH-associated lung infections. Adverse events were similar for the two groups.

"This is a preliminary pilot study with a small number of patients not completely randomized and blinded so any results and conclusions have to be taken as preliminary," Dr. Kevin Sheth of Yale University School of Medicine in New Haven, Connecticut, who co-authored an editorial accompanying the study, told Reuters Health in a telephone interview. Nevertheless, Dr. Sheth called the approach "provocative."

"Their initial results seem to suggest that they do have decreased swelling in the brain after hemorrhage, and that this may translate into an improved clinical outcome," he added.

One caveat with fingolimod, he added, is that the drug is associated with cardiac effects, including bradycardia and heart block. "This population may potentially be at higher risk for secondary cardiac effects," Dr. Sheth said. "That would need to be monitored very closely in any future study."

The findings also underscore the importance of developing markers of swelling and inflammation in ICH patients, he added. "How we measure swelling is actually a big gap in knowledge. In order to successfully translate therapies like this in human patients, we need to better develop those markers as well."

SOURCE: http://bit.ly/1kMh2cV

JAMA Neurology 2014.

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