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Inhibitor development in previously treated hemophilia A patients: a systematic review, meta‐analysis, and meta‐regression
Author(s) -
Xi M.,
Makris M.,
Marcucci M.,
Santagostino E.,
Mannucci P. M.,
Iorio A.
Publication year - 2013
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12335
Subject(s) - meta analysis , medicine , cochrane library , confidence interval , subgroup analysis , medline , systematic review , incidence (geometry) , meta regression , biology , biochemistry , physics , optics
Summary Background The development of neutralizing alloantibodies (inhibitors) is the most serious complication of factor VIII ( FVIII ) replacement therapy in patients with hemophilia A . Unlike previously untreated patients, no definite risk factors for inhibitor development are known for previously treated patients ( PTP s). The investigation of the development of inhibitors in PTP s is hindered by several methodological limitations in the available literature. We conducted a systematic review to account for these limitations. Methods We considered the studies reporting on PTP s that were included in the W ight and P aisley meta‐analysis and a systematic search of MEDLINE , EMBASE , and The C ochrane L ibrary was conducted to identify studies published after 2003. Studies that investigated the development of inhibitors in hemophilia A PTP s who were treated with any type of FVIII concentrate and that included at least 25 patients with follow‐up were included in the analysis. Results Thirty‐three independent cohorts of PTP s with 4323 subjects and 43 incident de novo inhibitors were found and analyzed. The pooled incidence rate of inhibitor development for the 25 studies providing data on follow‐up was 3 (95% confidence interval 1–4) per 1000 person‐years. A significant association was not found between putative risk factors and inhibitor development in PTP s at meta‐regression analysis and subgroup analysis, but the model was sensitive enough to the inclusion of the reports on the B elgian‐ D utch experience with a highly immunogenic factor VIII . Conclusion We confirmed a low overall rate of de novo inhibitors in PTP s, without any significant effect of putative predictors, including the type of factor VIII concentrate.