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- Title
Pegcetacoplan for refractory paroxysmal nocturnal haemoglobinuria associated with the C5 genetic variant.
- Authors
Tamura, Shinobu; Hori, Yoshikazu; Hiroi, Takayuki; Morimoto, Masaya; Yamashita, Yusuke; Mushino, Toshiki; Sonoki, Takashi
- Abstract
Keywords: paroxysmal nocturnal hemoglobinuria; C5 genetic variant; refractory; eculizumab; pegcetacoplan EN paroxysmal nocturnal hemoglobinuria C5 genetic variant refractory eculizumab pegcetacoplan e57 e60 4 03/22/22 20220315 NES 220315 Anti-C5 antibodies effectively inhibit intravascular haemolysis, alleviate various symptoms associated with haemolysis and prevent thrombosis in most cases with paroxysmal nocturnal haemoglobinuria (PNH), thereby significantly improving the quality of life.1,2 However, some PNH cases are poor responders to anti-C5 antibody therapy and show poor prognosis.3-5 The common cause is the C3-mediated extravascular haemolysis; thus, C3 inhibitor as a possible therapeutic target has been developed specifically for them.3-7 Another cause of the refractoriness to treatment is the C5 genetic variant in a small population of PNH patient cases.3 Nishimura I et al i . identified a single missense heterozygous mutation in the C5 gene (c.2654G->A) in 11 Japanese PNH patient cases (corresponding to 3-2% of the Japanese PNH patient population) poorly responding to eculizumab. The mutation occurs in approximately 1% of the Han Chinese population.3 A very similar mutation in the C5 gene (c.2653C->T) has also been described in an Argentinian PNH patient, who was refractory to eculizumab.3 Recently, a unique heterozygous variant in the C5 gene (c.2653C->A) was identified in a Caucasian PNH patient with a poor response.8 To date, approved options for carriers of the C5 genetic variant are limited. Moreover, the PEGASUS study demonstrated an advantage of pegcetacoplan in patients who had an inadequate response to eculizumab.10 In these patients, pegcetacoplan has the potential to control not only residual intravascular haemolysis but also C3-mediated extravascular haemolysis.
- Subjects
PAROXYSMAL hemoglobinuria; GENETIC variation; COMPLEMENT (Immunology)
- Publication
British Journal of Haematology, 2022, Vol 196, Issue 6, pe57
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.17963