Adding iptacopan leads to recovery in case of man with resistant iTTP
Drug sold as Fabhalta helped resolve severe blood disorder symptoms
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A man’s severe case of treatment-resistant immune thrombotic thrombocytopenic purpura (iTTP) — which resulted in severe anemia despite more than a week spent in a hospital’s intensive care unit — was successfully resolved after clinicans added the oral medication iptacopan to standard therapies.
That’s according to a case study from China that detailed the challenges of treating a young man with relapsed iTTP who was admitted to the hospital with both physical — bruises and red spots under the skin — and psychiatric symptoms. Standard treatment, including therapeutic plasma exchange (TPE), failed to ease his symptoms, the researchers noted.
After further investigation, the team turned to iptacopan, sold under the brand name Fabhalta, as an add-on treatment. Iptacopan is an approved therapy for adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder in which the immune system destroys red blood cells, among other indications.
Soon after starting the combination treatment, the man’s symptoms eased and his bloodwork began showing improved results, the researchers reported. His anemia, a condition marked by low red blood cell counts or low levels of hemoglobin, also was resolved. The iptacopan treatment and other medications were gradually tapered after the man’s hospital discharge, the team noted.
“This treatment strategy provides a complete practical example” for the use of iptacopan as a complementary therapy in certain iTTP case, the researchers wrote.
Case details were described in “The complement factor B inhibitor iptacopan for relapsed and refractory immune thrombotic thrombocytopenic purpura,” a study published in the Thrombosis Journal.
In iTTP, also called acquired TTP, the body’s immune system mistakenly attacks ADAMTS13, an enzyme that controls blood clotting. Without enough ADAMTS13 activity, tiny blood clots form throughout the body. These clots can damage organs, destroy red blood cells, and deplete platelets, the cell fragments that help blood clot normally.
Standard treatments fail to ease man’s symptoms
Available treatments aim to calm this abnormal immune response by combining immunosuppressive medications with TPE, a procedure that removes a patient’s plasma, the liquid portion of blood. In TPE, the patient’s plasma is replaced with healthy donor plasma, which helps eliminate harmful antibodies and restore the missing enzyme.
Some iTTP patients, however, may be refractory, meaning their disease does not fully respond to treatment, and go on to experience relapses, or a return of disease symptoms. Relapsed and refractory iTTP is particularly difficult to manage and carries an increased risk of poor outcomes, including death.
This study described the case of a young man with no prior history of chronic disease who developed severe relapsed and refractory iTTP, according to the researchers.
One year before the case report, he was admitted to the hospital after two days of altered consciousness. Blood tests showed a severe deficiency of ADAMTS13 activity, along with elevated antibodies targeting ADAMTS13. Further tests detected signs of red blood cell destruction and a very low platelet count, all leading to a diagnosis of iTTP.
He received immunosuppressive corticosteroids, TPE, plasma transfusions, and intravenous immunoglobulin (IVIG), a preparation made from pooled donor antibodies that can help suppress immune attacks.
At discharge, he showed signs of recovery, with improved platelet counts and levels of hemoglobin, the protein in red blood cells that carries oxygen.
Clinicians start man on iptacopan twice-daily
About seven months later, he was admitted to another hospital with disorganized speech, widespread tiny red spots under the skin (petechiae), and larger bruised areas (ecchymoses). Lab tests again showed signs of red blood cell destruction, ADAMTS13 deficiency, and anti-ADAMTS13 antibodies, and he was diagnosed with relapsed iTTP.
He received several TPE sessions along with IVIG, corticosteroids, and ripertamab, a therapy that depletes the immune B-cells responsible for producing antibodies, including those that cause disease. Even so, he continued to experience persistent agitation and psychiatric disturbances, suggesting the treatments were not adequately working.
Further emergency treatment with TPE, corticosteroids, antibiotics, and red blood cell transfusions did not stop the decline, the researchers noted. The man’s confusion and agitation worsened, and bruising became more extensive. CT scans revealed a partially collapsed lung and minor bleeding in the brain. Even after an additional nine days of intensive care, lab results still showed severe anemia and a worsening drop in platelets, the team noted.
To understand why treatments had failed and to explore additional options, the medical team measured two proteins, C5b-9 and factor B, linked to the complement cascade. The complement cascade is part of the immune system that, when overactivated, can damage the body’s own tissues. Elevated levels of both proteins confirmed that this pathway was involved in his disease.
Based on these findings, the man was started on twice-daily treatment with iptacopan, which suppresses abnormal complement activation. Alongside iptacopan, he continued to receive TPE, corticosteroids, and rituximab, another therapy that depletes antibody-producing B-cells, as well as sedation to manage agitation and transfusions of red blood cells and plasma.
Soon after starting this combination, his hemoglobin levels and platelet counts rose. He also showed marked neurological improvement, including restored alertness, resolution of agitation, and less fatigue. The extensive bruising on his limbs began to fade. Although his ADAMTS13 activity remained severely low, the anti-ADAMTS13 antibodies became undetectable.
Man’s condition satisfactory at hospital discharge
At discharge, his general condition was satisfactory, and he was sent home on oral iptacopan, as well as corticosteroids, which were gradually tapered throughout the follow-up period. By five weeks after discharge, his hemoglobin levels, platelet counts, and ADAMTS13 activity had all improved or normalized, the researchers noted.
This study “reports for the first time the potential association of combined therapy involving plasma exchange, corticosteroids, rituximab, and iptacopan with rapid clinical improvement in a patient with relapsed and refractory iTTP,” the team concluded. “It provides initial experience for exploring complement alternative pathway inhibition as a potential adjunctive strategy for such patients.”
