Inhibitor development in previously untreated patients with severe haemophilia: A comparison of included patients and outcomes between a clinical study and a registry-based study.

Autor: Jonker CJ; Dutch Medicines Evaluation Board (CBG-MEB), Utrecht, The Netherlands.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Oude Rengerink K; Dutch Medicines Evaluation Board (CBG-MEB), Utrecht, The Netherlands.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Hoes AW; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Mol PGM; Dutch Medicines Evaluation Board (CBG-MEB), Utrecht, The Netherlands.; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands., van den Berg HM; PedNet Haemophilia Research foundation, Baarn, The Netherlands.
Jazyk: angličtina
Zdroj: Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2020 Sep; Vol. 26 (5), pp. 809-816. Date of Electronic Publication: 2020 Jul 06.
DOI: 10.1111/hae.14100
Abstrakt: Aim: The aim of this study was to investigate whether a disease registry could serve as a suitable alternative to clinical studies to investigate safety of orphan drugs in children.
Methods: We used individual patient data from previously untreated patients (PUPs) with severe haemophilia A from the factor VIII (rAHF-PFM)-clinical study and the PedNet registry. The primary outcome was the patient characteristics at entry and the difference in inhibitor development between the clinical study and the registry-based study at 50 exposure days.
Results: Clinical study patients more often had a positive family history of inhibitors (31% vs 10%) and a high-risk F8 genotype (82% vs 63%). In the clinical study 41/55 (75%) and in the registry-based study 162/168 (96%) patients reached 50 exposure days. Inhibitors developed in 16 of the 41 patients in the clinical study (39%) vs 44 of the 162 patients in the registry-based study (27%); seven patients (7%) vs 28 patients (17%) had high-titre inhibitors. The risk of developing an inhibitor during the first 50 exposure days was similar (HR 1.04; 95% CI 0.56-1.94), when adjusted for family history of inhibitors, F8 gene mutation and intensive treatment at first exposure.
Conclusion: In the registry-based study, patient numbers and completeness of follow-up were higher. The risk of developing an inhibitor to a single product was comparable. Although the sample size of this study was too small to conclude on differences in high- or low-titre inhibitors, this suggests that a registry could serve as a more suitable source for evaluation of high-titre inhibitors in the setting of factor VIII deficiency.
(© 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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