A team led by researchers at Massachusetts General Hospital, a founding member of the Mass General Brigham health system, used a new drug to save the life of a patient with immune thrombotic thrombocytopenic purpura (iTTP), a rare disorder characterized by uncontrolled clotting throughout the body. small blood vessels. The group describes the first clinical use of the drug for iTTP in the New England Journal of Medicine.
“The drug is a genetically modified version of the enzyme missing in iTTP, and we showed that it was able to reverse the disease process in a patient with an extremely severe form of this condition,” said lead author Pavan K. Bendapudi. , MD. researcher in the Division of Hematology and Blood Transfusion Service at Massachusetts General Hospital and assistant professor of Medicine at Harvard Medical School.
iTTP is the result of an autoimmune attack against an enzyme called ADAMTS13 that is responsible for cleaving a large protein involved in blood clotting. The current mainstay of treatment for this potentially fatal blood disorder is plasma exchange, which removes harmful autoantibodies and provides additional ADAMTS13. Plasma exchange induces a clinical response in most patients, but at best can restore only about half of normal ADAMTS13 activity. In contrast, a recombinant form of human ADAMTS13 (rADAMTS13) offers the possibility of much higher ADAMTS13 delivery.
rADAMTS13 was recently approved for patients with congenital thrombotic thrombocytopenic purpura, which occurs in patients born with complete blood loss. ADAMTS13 gene. It is questionable whether rADAMTS13 could be effective in iTTP given the presence of inhibitory anti-ADAMTS13 autoantibodies, but Bendapudi and colleagues received permission from the US Food and Drug Administration to use rADAMTS13 donated by the manufacturer under a protocol for use. compassionate in a dying patient with refractory iTTP.
“We found that rADAMTS13 rapidly reversed this patient’s disease process despite current dogma that inhibitory autoantibodies against ADAMTS13 would render the drug useless in this condition,” Bendapudi said. “We were the first doctors to use rADAMTS13 to treat iTTP in the United States, and in this case, it helped save the life of a young mother.”
Bendapudi observed that the infused rADAMTS13 overcame inhibitory autoantibodies in the patient and reversed the thrombotic effects of iTTP. This impact was observed almost immediately after rADAMTS13 administration, after daily plasma exchange failed to induce remission.
“I believe that rADAMTS13 has the potential to replace the current standard of care in acute iTTP. We will need larger, well-designed trials to evaluate this possibility,” Bendapudi said.
A phase 2b randomized clinical trial of rADAMTS13 in iTTP was recently initiated.