More Than Half of Patients with PNH Are Receiving Higher Than Recommended Doses of Eculizumab

Patients with paroxysmal nocturnal hemoglobinuria (PNH) are often treated with C5 complement inhibitors, such as eculizumab. The standard dosage of eculizumab, administered via intravenous infusion, is 600 mg/week for the first four weeks (induction phase), 900 mg for the fifth dose one week later, and 900 mg biweekly thereafter (maintenance phase). However, a real-world study found that the majority of patients with PNH treated with eculizumab are started on an induction dose that is higher than the label-recommended dose, and the mean maintenance dose is higher than the label-recommended dose in approximately half of all patients. The results were presented at the 2020 ASH Annual Meeting.

The retrospective, longitudinal cohort study used provider-based claims data from the Symphony Health Integrated Dataverse and included 707 patients (mean age, 45.4 years; 55.7% were female; and 35.9% were from the south) aged ≥12 years with PHN who received two or more infusions of eculizumab between Oct. 1, 2014, and Sept. 30, 2019. The index date was defined as the first medical claim for eculizumab infusion with three or more months of prior continuous clinical activity, defined as one or more claim of any type per quarter (i.e., the baseline period).

Researchers assessed mean starting dose and the proportion with high (>600 mg), label-recommended (600 mg), and low (<600 mg) starting dose during the induction phase. In addition, the mean and mode dose during the induction and maintenance phases, as well as the proportion of patients with high, label-recommended, and low mean dose during the induction and maintenance phases, were assessed.

The mean observation period was 23.9 months. Most patients (77.1%) had commercial insurance. At baseline, 32.5% of patients had aplastic anemia, and 6.8% had myelodysplastic syndromes.

The most common comorbidities included hypertension (26.6%), coagulopathy (26.6%), and renal failure (20.5%). A majority of patients (85.1%) experienced anemia (other than aplastic anemia) at baseline.

The mean starting dose during the induction phase was 862 mg (standard deviation [SD], 412 mg); the proportion of patients with high, label-recommended, and low starting dose was 64.1%, 30.6%, and 5.4%, respectively. The mean and mode doses were 859 mg (SD, 391 mg) and 900 mg during the induction phase and 1,011 mg (SD, 333 mg) and 900 mg during the maintenance phase. The proportion of patients with a high, label-recommended, and low mean dose during the induction phase was 67.9%, 25.9%, and 6.2%, respectively, while the proportion of patients with a high, label-recommended, and low mean dose during the maintenance phase was 45.9%, 41.6%, and 12.5%, respectively.

“Future analyses that investigate budget impact of eculizumab in patients with PNH should account for real-world dosing patterns in order to comprehensively assess costs and benefits,” the researchers concluded.

Reference

Cheng WY, Sarda SP, Mody-Patel N, et al. Real-World Eculizumab Dosing Patterns Among Patients with Paroxysmal Nocturnal Hemoglobinuria in a US Population. Abstract 3412. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, Dec. 2-11, 2020.