Real-World Prevalence and Outcomes of Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors in the US: A Retrospective Claims Database Analysis.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder with C5 inhibitors (C5i), eculizumab and ravulizumab, being part of current treatment options.

Objectives: To estimate the 5-year prevalence of PNH and describe the healthcare resource utilization and direct healthcare costs associated with C5i among commercially insured patients with PNH treated with C5i in the US.

Methods: The 5-year prevalence of adults with PNH in IQVIA PharMetrics® Plus was estimated (2018-2022). A retrospective cohort study (2011-2022) was also conducted in adults with PNH treated with C5i and ≥3 months of continuous health plan coverage following the first claim for C5i (index date). PNH-related health resource utilization and direct healthcare costs were assessed from index date until earliest of treatment discontinuation/end of data/end of continuous health plan coverage (follow-up period).

Results: The 5-year prevalence of PNH was 2.4 per 100 000 persons in commercial claims. A total of 371 patients treated with C5i (median age: 40 years; female: 55.3%; eculizumab: 53.9%; ravulizumab: 46.1%) were followed for a mean ± SD [median] of 19.3 ± 16.9 [14.7] months. Annual incidence rates of PNH-related blood transfusion and breakthrough hemolysis (BTH) among patients treated with C5i were 1.2 (eculizumab: 1.3; ravulizumab: 1.0) and 4.5 (eculizumab: 5.2; ravulizumab: 3.3) per person per year (PPPY), respectively. In patients treated with eculizumab and ravulizumab, respectively, PNH-related blood transfusion was required by 46.2% and 11.9% of patients in the first 6 months post-index, and over the follow-up period, transfusion avoidance was observed in 46.2% and 78.2% of patients. The 6- and 12-month rates of PNH-related thrombosis were 8.0% and 10.6% for eculizumab and 6.1% and 11.6% for ravulizumab, respectively. Among patients treated with C5i, estimated annual total PNH-related costs PPPY were $660 533(eculizumab:$ 697 459; ravulizumab: $612 522)forthefirstyearand$ 633 984 (eculizumab: $691 022;ravulizumab:$ 570 832) for subsequent years, with treatment costs accounting for 94.3% to 94.6% of total costs.

Discussion: Despite treatment with C5i, patients with PNH still exhibited BTH, required blood transfusions, and experienced thrombosis.

Conclusion: This study highlights the unmet need for more effective PNH treatments to address the economic and clinical burden associated with PNH and improve disease control among patients.