Efficacy of iptacopan monotherapy for suboptimal response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria

Aim. To evaluate the hematological response within 4 weeks of iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria and suboptimal response to long-term eculizumab therapy.

Materials and methods. The analysis included 8 patients, median age 32 years, with persistent anemia on long-term therapy with eculizumab. The hematological response was assessed when switching to oral monotherapy with iptacopan 200 mg twice daily for 4 weeks.

Results. After 4 weeks of iptacopan therapy, an increase in hemoglobin levels by more than 20 g/l was achieved in 7/8 (88%), and a complete response in 6/8 (75%) patients. The median increase in hemoglobin levels was 32.5 g/l from the initial 85.5 g/l (74–100) to 121.5 g/l (80–141); p=0.00013. Independence from red blood cell transfusions was achieved in 100% of cases. Achieving a hematological response to iptacopan therapy was accompanied by a decrease in the level of absolute reticulocyte count, bilirubin and lactate dehydrogenase, as well as a negative result of the anti-C3d direct antiglobulin test.

Conclusion. The oral complement factor B inhibitor iptacopan is an effective treatment option for paroxysmal nocturnal hemoglobinuria in patients with a suboptimal response to complement inhibitor C5 due to more effective control of extravascular C3-mediated hemolysis.