Descriptive, real-world treatment patterns, resource use, and total cost of care among eculizumab- and ravulizumab-treated members with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, genetic, chronic, and life-threatening blood disease with an estimated prevalence of 13 per 1,000,000 persons reported in the United States. Available at analysis, PNH treatment included the use of C5 inhibitors (C5is), which prevent formation of membrane attack complex and consequently intravascular hemolysis. Limited real-world evidence suggests some individuals with PNH continue to experience anemia and breakthrough hemolysis (BTH) after C5i treatment, indicating unmet needs. To describe real-world treatment patterns and outcomes among individuals treated with C5is, eculizumab (ECU), and ravulizumab (RAV), focusing on affordability challenges and therapy unmet needs from a US payer perspective. This retrospective cohort study was conducted using deidentified data from Prime Therapeutics' approximately 15 million commercially insured US members with integrated medical and pharmacy claims data. Members were identified between January 1, 2018, and December 31, 2020. Inclusion criteria for cohort identification were adults aged 18 years or older at ECU or RAV index date requiring 2 or more claims for ECU or 1 or more claims for RAV. ECU and RAV users were excluded if they had a claim indicating treatment for a US Food and Drug Administration (FDA)-approved non-PNH indication. Members were required to be continuously enrolled 6 months before and 12 months after their index ECU or RAV claim. Real-world C5i claims-based treatment dosage and frequency patterns were compared with FDA-labeled dosing. Clinical outcomes, including transfusions and BTH events, were identified in the pre-index and post-index periods. Health care resource use and costs were calculated after network discounts, including member share. A total of 86 commercial members met analysis criteria: 34 in the ECU cohort and 52 in the RAV cohort. The mean age was 42.6 years, and 54.6% were female. Estimated higher-than-label PNH-recommended dosage occurred in 38.2% of ECU and 9.6% of RAV members. In total, 29.4% of ECU and 17.3% of RAV members had 4 or more transfusions in the post-index period. Additionally, 29.4% of ECU and 13.5% of RAV members had 1 or more BTH episodes. Post-index period mean per member total health care costs were $711,785 among ECU members and $624,911 among RAV members, and C5i costs accounted for 79.7% and 85.6% of total health care costs, respectively. Although all members received at minimum FDA-approved dosages, transfusions and BTH events continue to occur for some members. These findings indicate potentially inadequate therapy responses in a substantial subset of C5i users, adding additional therapy costs to an already extremely expensive therapy. This study was funded by Apellis Pharmaceuticals. Drs Broderick and Fishman report employment by Apellis Pharmaceuticals and own stock options. Dr Burke reports employment by Prime Therapeutics, LLC, which has received research funding from Apellis Pharmaceuticals. Dr Gleason reports employment by Prime Therapeutics, LLC, which has received research funding from Apellis Pharmaceuticals; serves on the advisory committee at the Institute for Clinical and Economic Review; and has served on the Board of Directors at the Academy of Managed Care Pharmacy.