Abstract introduction: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and life-threatening acquired hematopoietic stem cell disorder characterized by intravascular hemolysis, thrombosis, and hematopoietic failure. This condition arises from mutations in the PIG-A gene within hematopoietic stem cells, leading to a deficiency of critical complement-regulating proteins (CD55 and CD59) on the cell surface. Consequently, patients experience chronic hemolysis and immune cell activation, resulting in severe complications such as thrombosis, anemia, renal dysfunction, and various multi-systemic symptoms. (Bravo-Perez, 2023) Currently, complement inhibitors such as eculizumab and iptacopan are standard treatments; while eculizumab effectively inhibits C5 activation, it does not fully control intravascular hemolysis. (Wu, 2023) Ongoing research focuses on upstream complement inhibitors. Iptacopan, an oral factor B inhibitor, has demonstrated superior efficacy and safety in Phase III trials compared to C5 inhibitors, achieving greater increases in hemoglobin levels and reduced transfusion needs. This multicenter, retrospective cohort study aimed to assess the effectiveness and safety of complement inhibitors in real-world settings. Methods: From March 2025 to July 2025, we included 18 treatment-naïve PNH patients who were treated with iptacopan monotherapy in more than ten hospitals in Shandong Province, China. A stable treatment regimen was maintained for at least one month. The study had two primary endpoints: (1) the mean change in hemoglobin levels at Month 1 (Week 4), Month 2, and Month 3 for patients receiving iptacopan without requiring transfusions, and (2) the proportion of patients achieving hemoglobin normalization (≥12 g/dL) during follow-up without transfusions. The secondary endpoint focused on the mean change in lactate dehydrogenase (LDH) levels. Results: At Week 4, 11 patients were evaluable, and hemoglobin levels rose by an average of 27 g/L (95% CI: 5.72 to 49.00) from baseline, with no red blood cell transfusions required. Remarkably, 2 patients (18%; 95% CI: 2.3 to 51.8) achieved hemoglobin normalization, defined as having at least one hemoglobin level ≥12 g/dL during follow-up without transfusions. By the 2-month mark, 10 evaluable patients were assessed, showing a mean hemoglobin increase of 33 g/L (95% CI: 10.02 to 55.98) and no transfusion needs. Among these, 1 patient (10%; 95% CI: 0.25 to 44.50%) achieved normalization. At 3 months, 9 evaluable patients exhibited a mean hemoglobin increase of 36 g/L (95% CI: 20.84 to 52.04), also without transfusions. Here, 1 patient (11.1%; 95% CI: 0.28 to 48.24%) achieved hemoglobin normalization while remaining transfusion independent. As to the LDH levels at Week 4, a total of 8 evaluable patients showed a mean percent change of -67.4% from baseline (95% CI: -96.3 to -38.4). At Month 2, there was a mean percent change of - 60.8% (95% CI: -113.9 to -7.62) in the 6 evaluable patients. At Month 3, the remaining 3 evaluable patients exhibited the mean percent change of -89.4% (95% CI: -100.7 to -78.1). Discussion: Patients treated with iptacopan showed significant increases in hemoglobin levels and reductions in LDH, suggesting effective control of intravascular hemolysis. However, the normalization rate was low, possibly due to the study's short duration. In summary, iptacopan monotherapy effectively alleviates anemia symptoms and controls hemolysis in PNH patients.
Shuqian Xu (Mon,) studied this question.
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