Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria

Peter Hillmen, Petra Muus, Alexander Röth, Modupe O. Elebute, Antonio M. Risitano, Hubert Schrezenmeier, Jeffrey Szer, Paul Browne, Jaroslaw P. Maciejewski, Jörg Schubert, Alvaro Urbano-Ispizua, Carlos de Castro, Gérard Socié, Robert A Brodsky

Research output: Contribution to journalArticle

Abstract

Summary: Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival.

Original languageEnglish (US)
Pages (from-to)62-73
Number of pages12
JournalBritish Journal of Haematology
Volume162
Issue number1
DOIs
StatePublished - Jul 2013

Fingerprint

Paroxysmal Hemoglobinuria
Safety
Complement Activation
Hemolysis
Chronic Renal Insufficiency
Therapeutics
Antibodies, Monoclonal, Humanized
Survival
eculizumab
L-Lactate Dehydrogenase
Pulmonary Hypertension
Dyspnea
Abdominal Pain
Fatigue
Erythrocytes
Morbidity
Kidney

Keywords

  • Eculizumab
  • Haemolysis
  • Long-term therapy
  • Paroxysmal nocturnal haemoglobinuria
  • Phase III

ASJC Scopus subject areas

  • Hematology

Cite this

Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. / Hillmen, Peter; Muus, Petra; Röth, Alexander; Elebute, Modupe O.; Risitano, Antonio M.; Schrezenmeier, Hubert; Szer, Jeffrey; Browne, Paul; Maciejewski, Jaroslaw P.; Schubert, Jörg; Urbano-Ispizua, Alvaro; de Castro, Carlos; Socié, Gérard; Brodsky, Robert A.

In: British Journal of Haematology, Vol. 162, No. 1, 07.2013, p. 62-73.

Research output: Contribution to journalArticle

Hillmen, P, Muus, P, Röth, A, Elebute, MO, Risitano, AM, Schrezenmeier, H, Szer, J, Browne, P, Maciejewski, JP, Schubert, J, Urbano-Ispizua, A, de Castro, C, Socié, G & Brodsky, RA 2013, 'Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria', British Journal of Haematology, vol. 162, no. 1, pp. 62-73. https://doi.org/10.1111/bjh.12347
Hillmen, Peter ; Muus, Petra ; Röth, Alexander ; Elebute, Modupe O. ; Risitano, Antonio M. ; Schrezenmeier, Hubert ; Szer, Jeffrey ; Browne, Paul ; Maciejewski, Jaroslaw P. ; Schubert, Jörg ; Urbano-Ispizua, Alvaro ; de Castro, Carlos ; Socié, Gérard ; Brodsky, Robert A. / Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. In: British Journal of Haematology. 2013 ; Vol. 162, No. 1. pp. 62-73.
@article{1b38ff94b17148cb8997baadfae73832,
title = "Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria",
abstract = "Summary: Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6{\%}. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9{\%} at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8{\%}, with 96·4{\%} of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1{\%} of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0{\%} from baseline, with the number of red blood cell units transfused decreasing by 54·7{\%}. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival.",
keywords = "Eculizumab, Haemolysis, Long-term therapy, Paroxysmal nocturnal haemoglobinuria, Phase III",
author = "Peter Hillmen and Petra Muus and Alexander R{\"o}th and Elebute, {Modupe O.} and Risitano, {Antonio M.} and Hubert Schrezenmeier and Jeffrey Szer and Paul Browne and Maciejewski, {Jaroslaw P.} and J{\"o}rg Schubert and Alvaro Urbano-Ispizua and {de Castro}, Carlos and G{\'e}rard Soci{\'e} and Brodsky, {Robert A}",
year = "2013",
month = "7",
doi = "10.1111/bjh.12347",
language = "English (US)",
volume = "162",
pages = "62--73",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria

AU - Hillmen, Peter

AU - Muus, Petra

AU - Röth, Alexander

AU - Elebute, Modupe O.

AU - Risitano, Antonio M.

AU - Schrezenmeier, Hubert

AU - Szer, Jeffrey

AU - Browne, Paul

AU - Maciejewski, Jaroslaw P.

AU - Schubert, Jörg

AU - Urbano-Ispizua, Alvaro

AU - de Castro, Carlos

AU - Socié, Gérard

AU - Brodsky, Robert A

PY - 2013/7

Y1 - 2013/7

N2 - Summary: Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival.

AB - Summary: Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival.

KW - Eculizumab

KW - Haemolysis

KW - Long-term therapy

KW - Paroxysmal nocturnal haemoglobinuria

KW - Phase III

UR - http://www.scopus.com/inward/record.url?scp=84879121370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879121370&partnerID=8YFLogxK

U2 - 10.1111/bjh.12347

DO - 10.1111/bjh.12347

M3 - Article

VL - 162

SP - 62

EP - 73

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 1

ER -