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

Wendy Y Cheng,1 Sujata P Sarda,2 Nikita Mody-Patel,2 Sangeeta Krishnan,2 Mihran Yenikomshian,1 Colin Kunzweiler,1 Jensen Duy Vu,1 Hoi Ching Cheung,1 Mei Sheng Duh1 1Analysis Group, Inc., Boston, MA, USA; 2Apellis Pharmaceuticals, Inc., Waltham, MA, USACorrespondence: Wendy Y Cheng, Analysis Group, Inc., 111 Huntington Ave, 14th Floor, Boston, MA, 02199, USA, Tel +1 617 425 8219, Fax +1 617 425 8000, Email Wendy.Cheng@analysisgroup.comPurpose: 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.Keywords: complement inhibitors, dose escalation, dosing patterns, eculizumab, paroxysmal nocturnal hemoglobinuria