Complement C3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to C5 inhibitor therapy

The introduction of the complement component C5 inhibitor eculizumab has radically changed the prognosis and quality of life of patients with paroxysmal nocturnal hemoglobinuria. Up to 30 % of patients develop only a suboptimal response to C5 inhibition. One reason for this is activation of extravas...

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Main Authors: M. V. Marchenko, O. U. Klimova, E. V. Anikina, A. V. Lapina, T. A. Rudakova, T. I. Ksenzova, A. D. Kulagin
Format: Article
Language:Russian
Published: ABV-press 2024-09-01
Series:Онкогематология
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Online Access:https://oncohematology.abvpress.ru/ongm/article/view/938
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author M. V. Marchenko
O. U. Klimova
E. V. Anikina
A. V. Lapina
T. A. Rudakova
T. I. Ksenzova
A. D. Kulagin
author_facet M. V. Marchenko
O. U. Klimova
E. V. Anikina
A. V. Lapina
T. A. Rudakova
T. I. Ksenzova
A. D. Kulagin
author_sort M. V. Marchenko
collection DOAJ
description The introduction of the complement component C5 inhibitor eculizumab has radically changed the prognosis and quality of life of patients with paroxysmal nocturnal hemoglobinuria. Up to 30 % of patients develop only a suboptimal response to C5 inhibition. One reason for this is activation of extravascular hemolysis, due to opsonization of erythrocytes with fragments of the C3 component. Pegcetacoplan, the first ever registered C3 inhibitor, is aimed at solving this problem.In Russia, 2 patients received pegcetacoplan as part of a phase 3, randomized, open-label, active-comparator controlled trial PEGASUS. The analysis includes data from the first year of therapy: the run-in period (pegcetacoplan 1080 mg SC twice weekly in addition to the current dose of eculizumab, 4 weeks), the randomized controlled period (both patients were randomized to eculizumab monotherapy, 16 weeks), and the open-label period of pegcetacoplan therapy (32 weeks). Data from the extension study to evaluate the long-term safety and efficacy of pegcetacoplan are also presented. The duration of follow-up on pegcetacoplan therapy in both patients exceeded 4 years.
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spelling doaj-art-71420cfe4cba44df9b8161e886d0f53e2025-08-20T03:01:03ZrusABV-pressОнкогематология1818-83462413-40232024-09-01193687810.17650/1818-8346-2024-19-3-68-78765Complement C3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to C5 inhibitor therapyM. V. Marchenko0O. U. Klimova1E. V. Anikina2A. V. Lapina3T. A. Rudakova4T. I. Ksenzova5A. D. Kulagin6Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of RussiaRaisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of RussiaRegional Clinical Hospital No. 1Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of RussiaRaisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of RussiaRegional Clinical Hospital No. 1Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of RussiaThe introduction of the complement component C5 inhibitor eculizumab has radically changed the prognosis and quality of life of patients with paroxysmal nocturnal hemoglobinuria. Up to 30 % of patients develop only a suboptimal response to C5 inhibition. One reason for this is activation of extravascular hemolysis, due to opsonization of erythrocytes with fragments of the C3 component. Pegcetacoplan, the first ever registered C3 inhibitor, is aimed at solving this problem.In Russia, 2 patients received pegcetacoplan as part of a phase 3, randomized, open-label, active-comparator controlled trial PEGASUS. The analysis includes data from the first year of therapy: the run-in period (pegcetacoplan 1080 mg SC twice weekly in addition to the current dose of eculizumab, 4 weeks), the randomized controlled period (both patients were randomized to eculizumab monotherapy, 16 weeks), and the open-label period of pegcetacoplan therapy (32 weeks). Data from the extension study to evaluate the long-term safety and efficacy of pegcetacoplan are also presented. The duration of follow-up on pegcetacoplan therapy in both patients exceeded 4 years.https://oncohematology.abvpress.ru/ongm/article/view/938paroxysmal nocturnal hemoglobinuriacomplement c5 inhibitorsuboptimal responsecomplement c3 inhibitorpegcetacoplan
spellingShingle M. V. Marchenko
O. U. Klimova
E. V. Anikina
A. V. Lapina
T. A. Rudakova
T. I. Ksenzova
A. D. Kulagin
Complement C3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to C5 inhibitor therapy
Онкогематология
paroxysmal nocturnal hemoglobinuria
complement c5 inhibitor
suboptimal response
complement c3 inhibitor
pegcetacoplan
title Complement C3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to C5 inhibitor therapy
title_full Complement C3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to C5 inhibitor therapy
title_fullStr Complement C3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to C5 inhibitor therapy
title_full_unstemmed Complement C3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to C5 inhibitor therapy
title_short Complement C3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to C5 inhibitor therapy
title_sort complement c3 inhibitor in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to c5 inhibitor therapy
topic paroxysmal nocturnal hemoglobinuria
complement c5 inhibitor
suboptimal response
complement c3 inhibitor
pegcetacoplan
url https://oncohematology.abvpress.ru/ongm/article/view/938
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