INJECTION SITE REACTIONS in ADULT PATIENTS with PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO RECEIVED SUBCUTANEOUS PEGCETACOPLAN MONOTHERAPY for UP to 3 YEARS.
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All Authors
Arnold, L.
Czech, B.
Hillmen, P.
Kelly, R.
LTHT Author
Arnold, Louise
Kelly, Richard
Kelly, Richard
LTHT Department
Oncology
Haematology
PNH Service
Haematology
PNH Service
Non Medic
Advanced Clinical Practitioner
0
0
Publication Date
2024
Item Type
Conference Abstract
Language
Subject
ADULT , COMORBIDITY , CONTROLLED CLINICAL TRIALS AS TOPIC , ACTIVITIES OF DAILY LIVING , DRUG THERAPY, COMBINATION , DRUG DOSAGE CALCULATIONS , SELF ADMINISTRATION , DRUG THERAPY , FATIGUE , WOMEN , FOLLOW-UP-STUDIES , OUTCOME ASSESSMENT , HOSPITALISATION , INJECTIONS , MEN , HAEMOGLOBINURIA , PATIENT COMPLIANCE , CLINICAL TRIALS AS TOPIC , QUALITY OF LIFE , WORLD HEALTH ORGANIZATION
Subject Headings
Abstract
Background: Pegcetacoplan (PEG) is the first complement C3-targeted therapy for paroxysmal nocturnal hemoglobinuria (PNH). PEG improved hematological outcomes for patients with PNH in 2 Phase 3 trials: PEGASUS (NCT03500549) in complement C5 inhibitor (C5i)-experienced patients and PRINCE (NCT04085601) in C5i-naive patients. PEG is self-administered by subcutaneous (SC) injection, a method with potential for injection site reactions (ISRs). Aim(s): To assess ISR treatment-emergent adverse events (TEAEs) in an integrated analysis of PEG-treated patients from PEGASUS and PRINCE studies and the follow-up open-label extension study (307 OLE; NCT03531255) for up to 3 years. Method(s): Patients received PEG 1080 mg SC twice weekly, with dosage escalations allowed. In patients with a lactate dehydrogenase concentration of >2x the upper limit of normal (226 U/L), dosing frequency could be increased to every 3 days or 3 times weekly. Treatment compliance was the total number of doses received from initiation until data cut divided by the number of expected doses. Patients provided informed consent before participation. The number of patients with TEAEs, including ISR TEAEs, was measured from initiation of PEG monotherapy through 3 years (PEGASUS) or 2.5 years (PRINCE); ISR severity, as reported by investigators, was defined as mild (mild/passing discomfort not limiting activities; no treatment required), moderate (discomfort limiting daily activities; may have required treatment), or severe (significant symptoms prevented activities; may have required hospitalization/invasive intervention). Quality of life was assessed by mean (standard error [SE]) Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores from PEG initiation through 3 (PEGASUS) or 2.5 years (PRINCE) of PEG. Result(s): Of 132 patients in PEGASUS (N=80) and PRINCE (N=52), 114 (PEGASUS, n=64; PRINCE, n=50) enrolled in the 307 OLE. In PEGASUS patients (N=80), PEG dosing increased from twice weekly to every 3 days in 13 (16.3%) patients and from twice weekly to 3 times weekly in 7 (8.8%); in PRINCE patients (N=52), dosing increased from twice weekly to every 3 days in 9 (17.3%) and from twice weekly to 3 times weekly in 4 (7.7%). Overall, >92% had compliance of >=95%. Most patients from PEGASUS and PRINCE had a TEAE during 3 years of PEG monotherapy. Thrombotic events occurred in 3 (2.3%) patients (all in the context of multiple comorbidities while receiving PEG [n=2] or after PEG discontinuation [n=1]); no meningitis cases were reported. ISR rates decreased from 38.8% (Year 0-1) to 9.1% (Year 2-3) in PEGASUS patients and from 17.3% (Year 0-1) to 9.1% (Year 2-2.5) in PRINCE; most ISRs were mild (Table). There were no serious ISRs and no ISR-related discontinuations. As ISRs decreased with continued PEG, FACIT-Fatigue scores increased from well below the population norm (43.6) at baseline to approaching/above the norm after up to 3 years of PEG, showing reduced fatigue. The mean (SE) FACIT-Fatigue in PEG-treated PEGASUS patients was 31.6 (1.3) at PEG initiation (n=80), 41.6 (1.2) at week 48 (n=66), and 37.6 (2.5) at year 3 (n=26); in PEG-treated PRINCE patients, scores were 36.6 (1.4) at initiation (n=52), 45.0 (1.1) at week 48 (n=40), and 45.5 (1.4) at year 2.5 (n=33). Summary/Conclusion: Most ISRs were mild; none led to treatment discontinuation. Over time, the percentage of patients reporting ISRs decreased, possibly because patients gained confidence with self-administration. These results, along with high compliance and decreased fatigue (evident from higher FACIT-Fatigue scores), suggest ISRs are likely not a barrier to PEG treatment. (Table present).
Journal
HemaSphere