Objectives: Treatment of paroxysmal nocturnal hemoglobinuria (PNH) includes C5 complement inhibitors ravulizumab and eculizumab. Ravulizumab dosing varies by weight and includes a loading dose, followed by maintenance doses given every 8 weeks via intravenous infusion. This study investigated real-world dosing patterns of eculizumab-naive and eculizumab-experienced patients with PNH receiving ravulizumab.

Methods: Patients with ≥2 infusions of ravulizumab between 6/21/2019–5/6/2021 and ≥6 months of prior continuous clinical activity were identified from Symphony Health Integrated Dataverse^® (IDV) claims data. Patients were categorized as eculizumab-naive or eculizumab-experienced based on treatment with eculizumab during the 6 months prior to ravulizumab initiation. As Symphony IDV does not record weight, patients were assumed to be ≥60 and <100 kg (“medium body weight”), consistent with mean weights in ravulizumab clinical trials and the US population. Dosing patterns were evaluated over the treatment period. Sensitivity analyses assuming patients were “low body weight” (≥40 to <60 kg) or “high body weight” (≥100 kg) were conducted.

Results: Of 433 patients identified (eculizumab-naive: 198; eculizumab-experienced: 235), mean age was 47 years and mean treatment duration was 11.8 months. Among eculizumab-naive patients, mean and mode loading dose was 3,581 and 3,300 mg, respectively, and higher than the label-recommended dose (2,700 mg). Proportions of patients with high, label-recommended, and low loading dose were 75%, 17%, and 8%, respectively. Average maintenance doses were comparable to label-recommended doses (3,300 mg); however, nearly 25% of patients received high average doses. Sensitivity analyses revealed similar trends: >64% of patients received a high loading dose. Proportion with high average maintenance dose was substantial when assuming patients had "low body weight" and negligible when assuming “high body weight”. Findings were largely consistent among eculizumab-experienced patients.

Conclusions: Deviations from label-recommended ravulizumab dosages, notably high loading dose irrespective of weight, may result from inadequate control of PNH in some patients.