Real-World Study of US Adults with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan

Abstract

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease characterized by complement-mediated hemolysis. OPERA is the first US longitudinal real-world study on C3 inhibitor therapy, known as pegcetacoplan. Methods: OPERA enrolled US patients with PNH, age ≥18, who were prescribed pegcetacoplan, and data were collected from routine care. Hemoglobin was reported by patients during regular follow-up (censored from transfusions). The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (0-52 score) and Patient-Reported Outcomes Measurement Information System scale for Cognitive Function Abilities (PROMIS-CF; 23.27-67.09 t-score) were completed electronically (low score = negative outcome). Patients self-reported incidence of healthcare resource utilization (HCRU). Results: By January 2024, 70 patients (mean age 44.6 years; 57.1% female) reported up to 9 months of pegcetacoplan treatment, with a median [IQR] follow-up of 6.6 [3.8] months. The latest reported hemoglobin levels improved by a mean (SD) of 2.6 (1.9) g/dL from baseline. At 3, 6 and 9 months, patients reported clinically meaningful improvements (≥5 points) in FACIT-F (53.3-69.0%) and (≥2 points) PROMIS-CF (46.7-55.2%). Patients reported a <10% incidence rate per person month of all HCRU events. Conclusions: This first longitudinal real-world US study indicates a positive trend in Hb, fatigue, and cognition with limited HCRU during pegcetacoplan treatment in adults with PNH.

Keywords: FACIT; OPERA; PROMIS; healthcare resource utilization; hemoglobin; quality of life; transfusions.

Figure 1

OPERA study design: patient selection and data collection. * Monthly contact between the patient and pharmacy was conducted regardless of study participation. Abbreviations: ePRO, electronic patient-reported outcomes; FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue; HCRU, healthcare resource utilization; PNH, Paroxysmal Nocturnal Hemoglobinuria; PROMIS-CF, Patient-Reported Outcome Measurement Information System v2.0—Cognitive Function Abilities Subset 8a; Tx, Treatment; PEG, pegcetacoplan.

Figure 2

OPERA subgroup analysis of average hemoglobin levels reported by treatment duration. Data depicts summary statistics during routine care and monitoring, which varies as directed by physicians. Hemoglobin was reported if/when this lab test was available; data were censored for transfusion events (all values provided after the first-reported intercurrent event were excluded from outcomes). * N = individual hemoglobin laboratory results reported during each period of treatment. ^ Line represents the lower limit of normal for hemoglobin values found for females in the general population. Current range: 4–39 weeks (1–9 months) of pegcetacoplan treatment. Over this period, the mean (SD) change from baseline by the latest reported hemoglobin level was 2.6 (1.9) g/dL. Abbreviations: LLN, lower limit of normal; SE, standard error.