BBB Leakiness Decrease May Predict Effectiveness of Lemtrada Treatment
Among multiple sclerosis (MS) patients starting on Lemtrada (alemtuzumab), an early decrease in the leakiness of the blood-brain barrier (BBB) is associated with a lower likelihood of disease activity after two years, according to a new study.
The blood-brain barrier is a cellular divisor that regulates which substances from the blood are able to pass into the brain.
“Here we report evidence that BBB permeability during [Lemtrada] treatment can be used as a predictor of treatment efficacy” researchers wrote. “This validates previous research indicating that BBB permeability is a marker of treatment response in relapsing-remitting multiple sclerosis.”
The study, “Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis,” was published in Multiple Sclerosis and Related Disorders. It was funded by Sanofi and The Danish Multiple Sclerosis Society.
In MS, the BBB becomes compromised and leaky. An emerging field of research is exploring whether its leakiness might be a useful biomarker for tracking MS progression or predicting the response to treatment.
A research team led by scientists in Denmark wanted to test whether measuring BBB permeability might be useful for predicting the response to treatment with Lemtrada, a disease-modifying MS therapy marketed by Sanofi.
“The aim of the present study was to investigate the effect of [Lemtrada] on the leakiness of the BBB and the predictive capabilities of individual BBB responses on subsequent disease activity,” the researchers wrote.
The study included 15 adults with relapsing-remitting MS who started on Lemtrada and were followed for two years.
Over the course of the study, participants underwent several evaluations with dynamic contrast enhanced MRI, a technique used to measure BBB permeability. By the end of follow-up, eight showed evidence of disease activity — four had new or enlarged brain lesions, and four experienced relapses.
The seven patients who did not have disease activity experienced a significantly greater decrease in BBB leakiness around the brain’s normal-appearing white matter (NAWM) in the first six and 12 months after starting on Lemtrada. The average difference was 0.029 ml/100 g/min at six months and 0.043 ml/100 g/min at 12 months.
White matter is a type of brain tissue that mainly contains connections among nerve cells. Some differences also were seen in BBB permeability around the brain’s gray matter, which contains nerve cell bodies.
“In the NEDA [no evidence of disease activity] group, we observed a significant decrease in [BBB permeability] from baseline to six months in both normal-appearing white matter (NAWM) and [gray matter]. Moreover, we also observed a significant decrease in [BBB permeability] from baseline to 12 months in NAWM in the NEDA group,” the researchers wrote.
Statistical analyses showed that measuring BBB leakiness could help predict the risk of disease activity. For example, at a cutoff of a 0.0178 decrease, BBB leakiness at six months predicted disease activity with a sensitivity (true-positive rate) of 88% and specificity (true-negative rate) of 76%.
“Our results indicate that treatment-associated changes in BBB permeability can be used as a surveillance tool of treatment response,” the researchers said.
The team emphasized that the small sample size was a limitation of the study. They noted that only 167 people with RRMS were given Lemtrada in Denmark between 2009 and 2019. Due to its safety profile, Lemtrada is usually reserved for MS patients who have not responded to other treatments.
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