Add-on Cablivi may may help boost cognitive recovery in iTTP: Study
Findings suggest treatment repaired damage to the blood-brain barrier
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Adding Cablivi (caplacizumab-yhdp) to standard treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) may help protect the brain by repairing damage to the blood-brain barrier, potentially reducing long-term cognitive problems, a study suggests.
The study, “Neurological Impact of Caplacizumab in Refractory iTTP Survivors: A Comparative Study of Blood-Brain-Barrier Integrity and Cognitive Outcomes,” was published in Arteriosclerosis, Thrombosis, and Vascular Biology by a group of researchers in Canada.
Cablivi targets von Willebrand factor to prevent blood clots
In iTTP, blood clots block small blood vessels throughout the body, particularly in the brain, the heart, and the kidneys. Patients are often treated successfully during an episode of iTTP, but many continue to experience long-term complications such as loss of memory.
It is believed that one reason for these long-term problems is damage to the blood-brain barrier, a protective layer of cells that controls what can enter the brain from the bloodstream. When damaged, harmful substances can leak into the brain, causing cognitive problems.
This study examined whether adding Sanofi’s Cablivi, an approved medication for iTTP, to standard treatment could prevent cognitive problems in patients with refractory disease. Refractory means the disease does not respond well to treatment.
In iTTP, blood clots form due to self-reactive antibodies against ADAMTS13, an enzyme that breaks down von Willebrand factor. This factor acts on platelets, causing them to stick together and form blood clots. Cablivi targets von Willebrand factor to prevent blood clots from forming.
These findings have important implications for patient care: they provide a scientific rationale for earlier, first-line use of [Cablivi]. The potential long-term reduction in cognitive [problems] could meaningfully improve quality of life and reduce health care costs in a predominantly working-age population.
The study (NCT03187652) included 16 patients. Seven received only standard treatment, while nine received standard treatment plus Cablivi. Standard treatment usually includes plasma exchange, which replaces a patient’s plasma (the noncellular part of blood) with healthy donor plasma, and immunosuppressing medications that reduce antibody production by immune cells. Patients who received Cablivi had failed to respond to plasma exchange and immunosuppression.
The researchers evaluated patients about a month after remission, when levels of platelets and lactate dehydrogenase (a potential sign of tissue damage) were normalized, and again about a year later. They used computed tomography perfusion imaging, a type of scan that measures blood flow and the leakiness of the blood-brain barrier by tracking the movement of fluid through it.
At the study’s start, patients treated with Cablivi showed greater blood-brain barrier damage than those receiving standard treatment alone. This suggests that patients treated with Cablivi initially had more severe, treatment-resistant disease.
Despite this, they showed significant improvement over the course of a year compared with patients receiving only standard treatment. Their blood-brain barrier was not as permeable, suggesting repair over time. In contrast, patients receiving just standard treatment showed little improvement.
The researchers also tested cognitive function using Creyos, a computerized tool that measures reasoning, memory, verbal memory, and concentration. Patients with more damage to their blood-brain barrier generally performed worse across all four cognitive domains. Lower ADAMTS13 activity was also linked to worse cognitive performance.
Although the study was small and not all patients received rituximab — an immunosuppressant marketed as Rituxan and also available as biosimilars — due to funding constraints, the findings suggest that protecting blood vessels in the brain during acute episodes of iTTP may reduce long-term cognitive problems.
“These findings have important implications for patient care: they provide a scientific rationale for earlier, first-line use of [Cablivi],” the researchers wrote. “The potential long-term reduction in cognitive [problems] could meaningfully improve quality of life and reduce health care costs in a predominantly working-age population,” they added.
