Adding Cablivi to standard treatment effective for acquired TTP: Study
Antibody-based therapy normalized platelet levels, improved clinical outcomes
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Adding Cablivi (caplacizumab) to therapeutic plasma exchange (TPE) and corticosteroids may lead to a faster treatment response and durable disease remission in people with acquired thrombotic thrombocytopenic purpura (aTTP), according to a report.
The report describes the cases of three women in Slovakia, which showed that Cablivi contributed to faster normalization of platelet levels, reduced the number of TPE sessions and hospitalization time, and improved clinical outcomes.
“Our case reports present the effective administration of [Cablivi], immediately after starting TPE therapy in patients with newly diagnosed acute form of aTTP, including the first administration of [Cablivi] in Slovakia,” researchers wrote.
The study, “Effectiveness of caplacizumab in the first-line treatment for acquired thrombotic thrombocytopenic purpura: single center experience,” was published in Therapeutic Advances in Hematology.
Cablivi targets protein involved in blood clotting
TTP is characterized by the formation of small blood clots in blood vessels due to reduced activity of the ADAMTS13 enzyme, which normally prevents platelets from forming blood clots when they aren’t needed. Acquired, or immune-mediated, TTP is caused by self-reactive antibodies that inhibit the enzyme’s activity. In aTTP, the first acute disease episode usually occurs in adulthood.
Treatment most commonly involves therapeutic plasma exchange (TPE), a procedure wherein a person’s plasma is removed and replaced with healthy donor plasma to help remove self-reactive antibodies and provide functional ADAMST13, and immunosuppressive therapy with corticosteroids. Cablivi, an antibody-based therapy targeting von Willebrand factor (VWF), a protein involved in blood clotting, may also be used to manage the disease alongside TPE and corticosteroids.
In this study, researchers in Slovakia analyzed data from three women, ages 44 to 66 years, newly diagnosed with acute aTTP. They had moderate to severe anemia (low levels of red blood cells or hemoglobin, the protein that carries oxygen in red blood cells) and severe thrombocytopenia (low platelet counts, or cell fragments that are key for clotting). One, a 60-year-old, also had acute kidney injury, whereas the other two had neurological symptoms.
Due to suspected TTP, researchers calculated the PLASMIC score, which assesses factors such as platelet count, red blood cell destruction, and transplant history. It indicated an intermediate-to-high risk of severe ADAMST13 deficiency. Additionally, all three women had ADAMTS13 activity below 2% and ADAMTS13-targeting antibodies.
Signs of hemolysis, or red blood cell destruction, included increased lactate dehydrogenase and bilirubin levels, decreased haptoglobin levels, and the presence of immature red blood cells. Results in all three women also showed elevated levels of d-dimers, protein fragments produced when blood clots break down. Large vWF multimers, which induce platelet aggregation into blood clots, were found in one patient.
It may be an option to start the treatment with [Cablivi] and immunosuppressive therapy without TPE.
After diagnosis, all three women started treatment with TPE and high-dose corticosteroids. Two women also received red blood transfusions to treat anemia. Cablivi was added four to nine days after symptom onset.
After normalization of platelet counts, LDH levels, and ADAMST13 activity, which occurred 10 to 13 days after symptom onset, TPE sessions were stopped, and the corticosteroid dose was gradually reduced. Women continued receiving daily Cablivi treatment for a total of 38 to 43 doses.
Clinical remission was achieved later in all patients, who were discharged after 16 to 28 days of hospitalization.
Two patients experienced aTTP exacerbations, and one patient experienced an aTTP relapse after discharge, with mild platelet reduction and low ADAMTS13 activity, but without the formation of blood clots. These episodes were successfully treated with the immunosuppressants rituximab or cyclophosphamide.
According to the researchers, these results suggest that “it may be an option to start the treatment with [Cablivi] and immunosuppressive therapy without TPE.”
“There was a rapid response to treatment and complete long-term remission was achieved,” they concluded.
