Eculizumab Dosing Intervals Longer than 17 Days May Be Associated with Greater Risk of Breakthrough Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria

被引：44

作者：

Nakayama, Hirokazu ^{[1
]}

Usuki, Kensuke ^{[2
]}

Echizen, Hirotoshi ^{[3
]}

Ogawa, Ryuichi ^{[3
]}

Orii, Takao ^{[1
]}

机构：

[1] NTT Med Ctr Tokyo, Dept Pharm, Shinagawa Ku, 5-9-22 Higashi Gotanda, Tokyo 1418625, Japan

[2] NTT Med Ctr Tokyo, Dept Hematol, Shinagawa Ku, 5-9-22 Higashi Gotanda, Tokyo 1418625, Japan

[3] Meiji Pharmaceut Univ, Dept Pharmacotherapy, 2-522-1 Noshio, Kiyose, Tokyo 2048588, Japan

来源：

BIOLOGICAL & PHARMACEUTICAL BULLETIN | 2016年 / 39卷 / 02期

关键词：

eculizumab; dosing interval; breakthrough hemolysis; paroxysmal nocturnal hemoglobinuria; COMPLEMENT INHIBITOR ECULIZUMAB; TERM SAFETY;

D O I：

10.1248/bpb.b15-00703

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Eculizumab given bi-weekly is widely recommended for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). We undertook a retrospective analysis on the medical records of 763 dosings of 14 PNH patients to investigate whether a threshold would exist in dosing intervals associated with breakthrough hemolysis. We identified 12 events of breakthrough hemolysis in 4 patients. Multivariate logistic regression and receiver operating characteristics (ROC) analysis revealed a significant association between increased risk of breakthrough hemolysis and prolonged dosing intervals of 17 days or more and concomitant inflammation: odds ratios (OR) and 95% confidence intervals (CIs) were 1.6 (1.3-2.0, p<0.01) and 5.5 (1.3-22.8, p=0.02), respectively. ROC analysis showed that the best cut-off dosing interval discriminating breakthrough hemolysis was 16.5 days. We consider that eculizumab dosing intervals longer than 17 days may be associated with an increased risk for developing breakthrough hemolysis in patients with PNH.

引用

页码：285 / 288

页数：4

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