Real-World Drug Adherence, Persistence, and Healthcare Resource Utilization in Patients with Paroxysmal Nocturnal Hemoglobinuria in the USA: The Advantage Study

Background

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by uncontrolled terminal complement activation. Treatment with terminal complement inhibitors ravulizumab or eculizumab has led to improved clinical outcomes for patients with PNH. Evidence on real-world treatment patterns and healthcare resource utilization (HRU) in this patient population, which includes emerging data on pegcetacoplan, is limited.

Objective

To describe real-world drug adherence and persistence in patients with PNH receiving ravulizumab, eculizumab or pegcetacoplan, and compare HRU for patients pre- and post-ravulizumab initiation in the USA.

Methods

ADVANTAGE is a retrospective, longitudinal analysis using the Komodo Health Research Database, a large multi-payer US health insurance claims dataset, among patients with PNH and ≥ 1 claim for ravulizumab, eculizumab or pegcetacoplan. Patients aged ≥ 18 years at index date (defined as the date of first claim for a given complement inhibitor on/after 1 January, 2019), with ≥ 12 months enrollment prior to this date, ≥ 1 claim with an ICD-10-CM code indicating PNH prior to/at index date and no ICD-10-CM code suggesting an alternative indication, were included. Patients were followed until the end of continuous enrollment, death, or end of data availability. Adherence was assessed by proportion of days covered (PDC) and treatment duration was estimated using Kaplan-Meier analysis. The HRU analysis included patients with ≥ 12 months follow-up and compared rates of HRU per-patient per-year (PPPY) in the 12 months pre- and post-ravulizumab treatment initiation. Pre-post differences in HRU were estimated using generalized estimating equations with robust standard errors.

Results

The sample included 344, 342 and 97 patients with index treatments for ravulizumab, eculizumab or pegcetacoplan, respectively. Age and sex distribution of patients were similar among patients treated with ravulizumab (mean age: 44 years; 57% female), eculizumab (mean age: 44 years; 60% female), or pegcetacoplan (mean age: 45 years; 62% female). More patients in the ravulizumab cohort were complement inhibitor-naive (31%) compared with eculizumab (20%) or pegcetacoplan (24%). Mean (standard deviation [SD]) duration of follow-up was 25.3 (15.9), 33.5 (18.9) and 13 (8.0) months, and mean (SD) proportion of days covered (PDC) was 0.98 (0.05), 0.90 (0.14) and 0.77 (0.30) for the ravulizumab, eculizumab and pegcetacoplan cohorts, respectively. The percentage of patients with PDC ≥ 0.8 (a widely used threshold for treatment adherence) was 98.5% for ravulizumab, and 84.5% and 78.4% for eculizumab and pegcetacoplan, respectively. The median (interquartile range [IQR]) duration on ravulizumab treatment was 48.4 (11.5, not reached [NR]) months, compared with 7.6 (3.4, 23.3) for eculizumab and 14.6 (0.2, NR) for pegcetacoplan.

Among patients with ≥ 12 months on ravulizumab treatment (n = 183), a 24.8% reduction in all-cause HRU was observed during the first 12 months of treatment compared with the prior 12 months. Statistically significant reductions were observed in mean (SD) all-cause hospitalizations (0.2 [0.6] PPPY during follow-up; % difference -44.6%, p = 0.014), outpatient visits (24.3 [17.8] PPPY; % difference -19.1%, p < 0.001) and emergency room visits (0.5 [1.3] PPPY; % difference -39.8%, p = 0.008). Similar results were observed for PNH-related HRU, including a 32.1% reduction in the overall number of visits (p < 0.001). Notably, a statistically significant reduction in PNH-related hospitalizations (0.2 [0.5] PPPY; % difference -37.8%, p = 0.044) and outpatient visits (14.3 [10.7] PPPY; % difference -22.4%, p < 0.001) was observed. Ravulizumab initiation was also associated with fewer PNH-related emergency room visits (0.2 [0.7] PPPY; % difference -32.7%, p = 0.170) and blood transfusions (0.8 [2.9] PPPY; % difference -30.7%, p = 0.277); however, these changes were not statistically significant.

Conclusions

In this retrospective analysis, patients demonstrated higher adherence and persistence to ravulizumab treatment compared to other complement inhibitors. HRU decreased following ravulizumab initiation, indicating an alleviated burden of disease in these patients after treatment initiation. These real-world data provide further evidence of the benefit of ravulizumab in patients with PNH.

Griffiths:MedscapeLive: Honoraria; MediCom Worldwide: Honoraria; AAMDS: Honoraria; MJH Health: Honoraria; ASH: Honoraria; MDS International Foundation: Honoraria; Physicians Educational Resource: Honoraria; Abbvie: Consultancy; Apellis Pharmaceuticals: Consultancy, Research Funding; Takeda Oncology: Consultancy; Astex Pharmaceuticals/Taiho Oncology/Otsuka: Consultancy, Research Funding; Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; CTI Biopharma: Consultancy; Novartis: Consultancy, Research Funding; Partner Therapeutics: Consultancy; Picnic Health: Consultancy; Servier: Consultancy; Blueprint Medicines: Research Funding; Celldex Pharmaceuticals: Research Funding; Genentech: Consultancy, Research Funding; NextCure: Research Funding; Alexion Pharmaceuticals/ AstraZeneca Rare Disease: Consultancy, Research Funding. Messali:Alexion, AstraZeneca Rare Disease: Current Employment. Mahdi:Alexion, AstraZeneca Rare Disease: Current Employment. DerSarkissian:Analysis Group Inc: Current Employment. Chang:Analysis Group Inc: Current Employment. Rabideau:Analysis Group Inc: Current Employment. Dingli:Sorrento: Consultancy, Honoraria; K36 Therapeutics: Research Funding; Janssen: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Genentech: Consultancy; Novartis: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Apellis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Alexion: Consultancy, Honoraria.