Inhibitor development according to concentrate in severe hemophilia: reporting on 1392 Previously Untreated Patients from Europe and Canada

被引：8

作者：

Fischer, Kathelijn ^{[1
,16
]}

Lassila, Riitta ^{[2
]}

Peyvandi, Flora ^{[3
,4
]}

Gatt, Alexander ^{[5
]}

Hollingsworth, Rob ^{[6
]}

Lambert, Thierry ^{[7
]}

Kaczmarek, Radek ^{[8
,9
]}

Bettle, Amanda ^{[10
]}

Samji, Nasrin ^{[11
]}

Rivard, Georges-etienne ^{[12
]}

Carcao, Manuel ^{[13
]}

Iorio, Alfonso ^{[14
]}

Makris, Mike ^{[15
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Ctr Benign Haematol Thrombosis & Haemostasis, Van Creveldklin, Utrecht, Netherlands

[2] Univ Helsinki, Dept Hematol, Unit Coagulat Disorders, Cent Hosp, Helsinki, Finland

[3] Fdn IRCCS CaGranda Osped Maggiore Policlin, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy

[4] Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy

[5] Mater Dei Hosp, Tal Qroqq, Msida, Malta

[6] MDSAS, Manchester, England

[7] Hop Bicetre, Paris, France

[8] World Federat Hemophilia, Coagulat Prod Safety Supply & Access Comm, Montreal, PQ, Canada

[9] Indiana Univ Sch Med, Wells Ctr Pediat Res, Indianapolis, IN USA

[10] IWK Hlth Ctr, Halifax, NS, Canada

[11] McMaster Univ, Dept Pediat, Div Hematol Oncol, Hamilton, ON, Canada

[12] Univ Montreal, Dept Pediat, Div Hematol Oncol, CHU St Justine, Montreal, PQ, Canada

[13] Hosp Sick Children, Div Haematol Oncol, Toronto, ON, Canada

[14] McMaster Univ, Dept Clin Epidemiol & Biostat, Toronto, ON, Canada

[15] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, England

[16] Univ Med Ctr Utrecht, Van Creveldklin, POB 85500, NL-3508 GA Utrecht, Netherlands

来源：

RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS | 2023年 / 7卷 / 08期

关键词：

antibodies; factor VIII; hemophilia A; hemophilia B; neutralizing; registries; FACTOR-VIII PRODUCTS; EMICIZUMAB PROPHYLAXIS; EUHASS; BOYS; METAANALYSIS;

D O I：

10.1016/j.rpth.2023.102265

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant.Objectives: To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B.Methods: The European Haemophilia Safety Surveillance (EUHASS) and Canadian Bleeding Disorders Registry (CBDR) have been monitoring adverse events overall and according to concentrate for 11 and 8 years, respectively. Inhibitors were reported quarterly, and PUPs completed 50 exposure days without inhibitor development annually. Cumulative inhibitor incidences and 95% confidence intervals (CIs) were compared without adjustment for other risk factors.Results: Fifty-six European and 23 Canadian centers reported inhibitor development in 312 of 1219 (26%; CI, 23%-28%) PUPs with severe hemophilia A and 14 of 173 (8%; CI, 5%-13%) PUPs with severe hemophilia B. Inhibitor development was lower on plasma -derived factor (F)VIII (pdFVIII, 20%; CI, 14%-26%) than on standard half-life recom-binant FVIII (SHL-rFVIII, 27%; CI, 24%-30% and odds ratio, 0.67; CI, 0.45%-0.98%; P = .04). Extended half-life recombinant FVIII (EHL-rFVIII, 22%; CI, 12%-36%) showed an intermediate inhibitor rate, while inhibitor rates for Advate (26%; CI, 22%-31%) and Kogenate/Helixate (30%; CI, 24%-36%) overlapped. For other SHL-rFVIII concentrates, inhibitor rates varied from 3% to 43%. Inhibitor development was similar for pdFIX (11%; CI, 3%-25%), SHL-rFIX (8%; CI, 3%-15%), and EHL-rFIX (7%; CI, 1%-22%).Conclusion: While confirming expected rates of inhibitors in PUPs, inhibitor develop-ment was lower in pdFVIII than in SHL-rFVIII. Preliminary data suggest variation in inhibitor development among different SHL-rFVIII and EHL-rFVIII concentrates.

引用

页数：10

共 30 条

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