Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon blood condition caused by complement-mediated hemolysis. In early clinical studies, iptacopan, an oral factor B inhibitor, showed promise in treating PNH. This systematic review aimed to compile information on the effectiveness and safety of iptacopan for PNH. A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The Medline, Embase, PubMed, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies that evaluated iptacopan for PNH. The primary efficacy outcomes were hemoglobin and lactate dehydrogenase (LDH) changes. A fixed-effects model was used for the meta-analysis. Six studies (three prospective cohorts, two RCTs, and one non-randomized trial) were included, comprising 197 patients. Iptacopan therapy significantly increased hemoglobin levels (mean differences (MD) = 12.98 g/L; 95% CI: 11.82-14.13; p < 0.0001) and decreased LDH (MD = -83.55 IU/L; 95% CI: -83.77 to -83.34; p < 0.0001). Subgroup analyses revealed more significant hemoglobin increases in European vs. Asian populations, studies with baseline Hb > 10 g/dL vs. < 10 g/dL, and studies lasting > 24 weeks vs. ≤ 24 weeks. LDH decreases were more pronounced in studies with baseline LDH > 500 IU/L vs. < 500 IU/L. The incidence of adverse events ranged from 66% to 90%, with the most common being headache, nasopharyngitis, and diarrhea. Serious adverse events occurred in 0-20% of patients across studies. Only one patient withdrew because adverse effects were reported across all studies. Preliminary data support iptacopan's effectiveness in improving hemoglobin levels and lowering hemolysis in PNH, both as a monotherapy and in combination with usual treatment. The safety profile appears to be excellent, with a minimal incidence of major adverse events and treatment discontinuation. Further studies are needed to validate the effectiveness and safety of larger, longer-term trials. Iptacopan is a viable oral therapy option for PNH.