Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review

被引：236

作者：

Iorio, A. ^{[1
]}

Halimeh, S. ^{[3
]}

Holzhauer, S. ^{[2
]}

Goldenberg, N. ^{[4
,5
]}

Marchesini, E. ^{[1
]}

Marcucci, M. ^{[1
]}

Young, G. ^{[6
]}

Bidlingmaier, C. ^{[10
]}

Brandao, L. R. ^{[9
]}

Ettingshausen, C. E. ^{[11
]}

Gringeri, A. ^{[7
]}

Kenet, G. ^{[12
]}

Knoefler, R. ^{[13
]}

Kreuz, W. ^{[11
]}

Kurnik, K. ^{[10
]}

Manner, D. ^{[8
]}

Santagostino, E. ^{[7
]}

Mannucci, P. M. ^{[7
]}

Nowak-Goettl, U. ^{[8
]}

机构：

[1] Univ Perugia, Hemophilia Ctr, I-06100 Perugia, Italy

[2] Charite, Dept Pediat Hematol Oncol, Berlin, Germany

[3] Med Thrombosis & Hemophilia Treatment Blood Trans, Duisburg, Germany

[4] Univ Colorado, Dept Pediat Hematol Oncol BMT, Denver, CO 80202 USA

[5] Childrens Hosp, Denver, CO 80218 USA

[6] Childrens Hosp, Div Hematol Oncol, Los Angeles, CA 90027 USA

[7] Mangiagalli & Regina Elena Fdn, Dept Med & Med Specialties, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, IRCCS Maggiore Hosp, Milan, Italy

[8] Univ Hosp Munster, Dept Pediat Hematol Oncol, Munster, Germany

[9] Hosp Sick Children, Dept Pediat Hematol Oncol, Toronto, ON M5G 1X8, Canada

[10] Univ Hosp Munich, Dept Pediat, Munich, Germany

[11] Univ Hosp Frankfurt, Dept Pediat Hematol Oncol, Frankfurt, Germany

[12] Chaim Sheba Med Ctr, Israel Natl Hemophilia Ctr, IL-52621 Tel Hashomer, Israel

[13] Univ Hosp Dresden, Dept Pediat Hematol Oncol, Dresden, Germany

来源：

JOURNAL OF THROMBOSIS AND HAEMOSTASIS | 2010年 / 8卷 / 06期

关键词：

factor VIII concentrates; hemophilia A; inhibitor development; previously untreated patients; systematic review; PROPHYLAXIS; FVIII; EPIDEMIOLOGY; PRODUCTS; CARE;

D O I：

10.1111/j.1538-7836.2010.03823.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Different rates of inhibitor development after either plasma-derived (pdFVIII) or recombinant ( rFVIII) FVIII have been suggested. However, conflicting results are reported in the literature. Objectives: To systematically review the incidence rates of inhibitor development in previously untreated patients (PUPs) with hemophilia A treated with either pdFVIII or rFVIII and to explore the influence of both study and patient characteristics. Methods: Summary incidence rates (95% confidence interval) from all included studies for both pdFVIII and rFVIII results were recalculated and pooled. Sensitivity analysis was used to investigate the effect of study design, severity of disease and inhibitor characteristics. Meta-regression and analysis-of-variance were used to investigate the effect of covariates ( testing frequency, follow-up duration and intensity of treatment). Results: Two thousand and ninety-four patients ( 1965 treated with pdFVIII, 887 with rFVIII; median age, 9.6 months) from 24 studies were investigated and 420 patients were observed to develop inhibitors. Pooled incidence rate was 14.3% (10.4-19.4) for pdFVIII and 27.4% (23.6-31.5) for rFVIII; high responding inhibitor incidence rate was 9.3% (6.2-13.7) for pdFVIII and 17.4% (14.2-21.2) for rFVIII. In the multi-way ANOVA study design, study period, testing frequency and median follow-up explained most of the variability, while the source of concentrate lost statistical significance. It was not possible to analyse the effect of intensity of treatment or trigger events such as surgery, and to completely exclude multiple reports of the same patient or changes of concentrate. Conclusions: These findings underscore the need for randomized controlled trials to address whether or not the risk of inhibitor in PUPs with hemophilia A differs between rFVIII and pdFVIII.

引用

页码：1256 / 1265

页数：10

共 23 条

[1] Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized [J].