Real-World Eculizumab Dosing Patterns Among Patients with Paroxysmal Nocturnal Hemoglobinuria in a US Population.

Purpose: Current pharmacologic management of paroxysmal nocturnal hemoglobinuria (PNH) consists of C5 inhibitors, eculizumab and ravulizumab; however, because patients experience incomplete symptom control, off-label doses may be utilized. We conducted a retrospective, longitudinal cohort study of provider-based claims data to assess the real-world eculizumab dosing patterns in PNH patients.
Patients and Methods: Patients were ≥12 years, received ≥2 eculizumab infusions between January 1, 2015 and September 30, 2019, and had ≥3 months of continuous clinical activity prior to index. The index date was the first claim for eculizumab. Patients with ≥1 diagnosis of another indication for eculizumab were excluded. Treatment patterns including the proportion with high, label-recommended, and low dosages during induction (first 28 days) and maintenance (beginning day 29) phases were described. The proportion and time-to-first dose escalation, defined as an increase in dose or frequency of infusion, were assessed among a subset of patients (ie, escalation analysis cohort).
Results: A total of 707 patients were examined. Mean (standard deviation [SD]) starting dose was 862mg (412mg) and was higher than label-recommended 600mg for 64% of the patients. Mean (SD) dose per infusion was 859mg (391mg) during the induction phase; average dose was higher than label-recommended 600mg for 68%. Mean (SD) dose per infusion during the maintenance phase was 1005mg (335mg); average dose was higher than label-recommended 900mg for 43%. Dose escalation occurred in 40/121 escalation analysis cohort patients. Median time-to-first dose escalation was ~12 months.
Conclusion: Results suggest that deviations from label-recommended dosing patterns were common. Future budget impact assessments of eculizumab should account for real-world dosing patterns to comprehensively assess costs and benefits.
Competing Interests: Sujata P Sarda, Nikita Mody-Patel, and Sangeeta Krishnan are employees of Apellis Pharmaceuticals, Inc. and own stock/stock options. Wendy Y Cheng, Mihran Yenikomshian, Jensen Duy Vu, and Mei Sheng Duh are employees of Analysis Group, Inc., which has received research funding from Apellis Pharmaceuticals, Inc. to conduct the current study. Colin Kunzweiler and Hoi Ching Cheung were employees of Analysis Group, Inc. during the conduct of this study. The authors report no other conflicts of interest in this work.
(© 2022 Cheng et al.)