Dosing Patterns of Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with Ravulizumab in the United States: A Retrospective Claims-Based Analysis.

Abstract

Complement factor5 inhibitors eculizumab and, recently, ravulizumab are standard therapies for paroxysmal nocturnal hemoglobinuria (PNH). However, some patients experience suboptimal response and may benefit from dosage adjustments. Ravulizumab is administered less frequently than eculizumab on the basis of patient's body weight. This retrospective analysis of insurance claims investigated ravulizumab dosing patterns among patients with PNH from the USA. Patients aged ≥ 12years with ≥ 2 ravulizumab infusions between June21, 2019 and May6, 2021, and ≥ 6months of continuous clinical activity prior to first ravulizumab infusion (index date) were identified from theSymphony Health Integrated Dataverse (IDV®) database. Observed mean (standard deviation, SD) ravulizumab doses administered were reported and stratified by previous eculizumab use. Scenarios adjusting for patients' body weights (unavailable in Symphony Health IDV) based on the US general population distribution were performed to estimate percentages of patients receiving label-recommended doses. Among 433 patients (mean [SD] age 47 [17]years), the mean (SD) loading dose was 3316.3 (2931.7)mg, greater than the maximal label-recommended loading dose (3000mg for patients ≥ 100kg). The mean (SD) loading doses were 3581.3 (3673.7)mg for eculizumab-naive versus 3093.1 (2096.8)mg for eculizumab-experienced patients. Over a mean (SD) treatment period of 11.8 (6.9)months, the mean (SD) average maintenance dose was 3403.7 (1024.4)mg, falling between label-recommended maintenance dose categories (3300mg for ≥ 60 to < 100kg; 3600mg for ≥ 100kg). Estimated percentages of patients receiving label-recommended loading and maintenance doses were 23.1% and 39.2%, respectively; 59.1% and 28.4% were estimated to receive above label-recommended loading and average maintenance doses, respectively. Although limited by missing clinical characteristics including body weight, this study of ravulizumab dosing patterns in patients with PNH identified potential deviations from label-recommended dosing, warranting further investigations of treatment response to complement inhibitors in PNH.