The complement factor B inhibitor iptacopan for relapsed and refractory immune thrombotic thrombocytopenic purpura.

backgroundThrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy, classified as congenital TTP (cTTP) and immune TTP (iTTP). iTTP represents the most common clinical subtype, accounting for approximately 95% of cases. Primary clinical features include microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neuropsychiatric symptoms, fever, and renal involvement. Reduced ADAMTS13 activity and dysregulation of the complement pathway contribute to the pathogenesis of iTTP. First-line therapy for newly diagnosed iTTP, comprising plasma exchange and corticosteroids, demonstrates reasonable efficacy. However, some patients experience disease relapse with suboptimal response to plasma exchange. These relapsed and refractory cases pose significant therapeutic challenges and are associated with an extremely poor prognosis and high mortality. CASE PRESENTATION: Here, we report a case of relapsed and refractory iTTP presenting with scleral icterus, thrombocytopenia, altered mental status, fever, and renal impairment. Despite initial treatment with plasma exchange, corticosteroids, ripertamab, and intravenous immunoglobulin, the patient’s condition deteriorated rapidly. Laboratory tests revealed elevated levels of the terminal complement complex (C5b-9) and complement factor Ba in the patient. Consequently, we initiated treatment with the complement inhibitor iptacopan, combined with plasma exchange, corticosteroids, and rituximab. The hemoglobin and platelet count increased significantly by Day 5. At the 5-week follow-up, ADAMTS13 activity, hemoglobin, and platelet counts had all normalised.

conclusionsThis case is a preliminary observation. With biomarker evidence supporting alternative pathway activation (e.g., elevated Ba and sC5b-9), it 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. It provides initial experience for exploring complement alternative pathway inhibition as a potential adjunctive strategy for such patients.