THROMBOSIS and MENINGOCOCCAL INFECTION RATES in PEGCETACOPLAN PATIENTS with PAROXYSMAL NOCTURNAL HEMOGLOBINURIA in the POST-MARKETING SETTING.
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All Authors
Panse, J.
Kelly, R.
Nishimori, H.
Horneff, R.
Hillmen, P.
Uchendu, U.
Zhang, D.
Lallier, S.
Gerber, G.
LTHT Author
Kelly, Richard
LTHT Department
Oncology
Haematology
Haematology
Non Medic
Publication Date
2024
Item Type
Conference Abstract
Language
Subject
ADULT , CAUSE OF DEATH , CLINICAL TRIALS AS TOPIC , CONTROLLED CLINICAL TRIALS AS TOPIC , DRUG THERAPY , WOMEN , FOLLOW-UP-STUDIES , HAEMOPHILUS INFLUENZAE , HEALTH PERSONNEL , MEN , MARKETING , NEISSERIA MENINGITIDIS , HAEMOGLOBINURIA , PATIENT COMPLIANCE , PRIMARY PREVENTION , PNEUMOCOCCAL INFECTIONS , THROMBOSIS , VACCINATION , ANTI-BACTERIAL AGENTS , ANTIBODIES, MONOCLONAL
Subject Headings
Abstract
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis, aplasia, and thrombosis. Before approval of complement inhibitors, thrombosis was the leading cause of death in patients with PNH. Complement inhibitors have subsequently decreased thrombosis rates in these patients. In patients who received the C5 inhibitor (C5i) eculizumab in clinical trials, thrombosis rates decreased from 7.37 events/100 patient-years before eculizumab treatment to 1.07 events/100 patient-years with eculizumab.[1] Treatment with the C5i ravulizumab had a similar thrombosis rate of 1.21 events/100 patient-years.[2] In clinical trials of pegcetacoplan, the first C3-targeted therapy approved for PNH, the thrombosis rate up to November 13, 2022, was 1.22 events/100 patient-years.[3] Optimal PNH treatment must block complement activity enough to reduce risk of thrombosis without compromising the complement system to an extent that increases the risk of life-threatening infections, especially Neisseria meningitidis. To achieve this fine balance, patient compliance with the recommended treatment dosing and risk-mitigating strategies for preventing infections are essential. Aim(s): To report the most current real-world rates of thrombosis and meningococcal infections in patients with PNH treated with pegcetacoplan in the post-marketing setting as of November 13, 2023. Method(s): We calculated the cumulative patient-year exposure to pegcetacoplan and reviewed compliance along with events of thrombosis (arterial and venous) and meningococcal infections in the post-marketing setting. Rates in the post-marketing setting were estimated from the total number of events reported in the Apellis/Swedish Orphan Biovitrum AB global safety database, using solicited reports from patient support and market research programs; spontaneous reports from health care providers, consumers, and regulatory agencies; and reports extracted from the literature. The trial protocols and label require vaccination against N meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae before pegcetacoplan use; the label recommends prophylactic antibiotic use if pegcetacoplan must be administered before vaccination. Informed consent was obtained before clinical trial participation. Result(s): Patients with PNH had experienced a total of 625.6 patient-years of pegcetacoplan exposure in the post-marketing setting (in the United States, Europe, and rest of the world) as of November 13, 2023. Compliance was estimated at 97%, with 96% of patients reporting they were confident in self-administering pegcetacoplan after receiving training. In the post-marketing setting, 2 thrombotic events occurred, resulting in a thrombosis rate of 0.32 events/100 patient-years (Table). No meningococcal infections were reported up to November 13, 2023, across countries in the post-marketing and clinical trial contexts (total 1, 127.3 patient-years). Summary/Conclusion: These findings suggest that the thrombosis rate on pegcetacoplan is low overall and comparable to rates on C5is in patients with PNH. A potential confounder is the real-world nature of the data, which may be subject to underreporting. There have been no reported meningococcal infections, suggesting effective risk mitigation strategies. Continued follow-up is required. (Table present).
Journal
HemaSphere