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

Carla J Jonker, Katrien Oude Rengerink, Arno W Hoes, Peter G M Mol, H Marijke van den Berg, Carla J Jonker, Katrien Oude Rengerink, Arno W Hoes, Peter G M Mol, H Marijke van den Berg

Abstract

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.

Keywords: factor VIII; haemophilia A; inhibitor development; previously untreated patients; registry.

Conflict of interest statement

All of the authors state that they have no financial or personal relationships that inappropriately influenced their role in this work. No funds for the content of this manuscript or the preparation of the manuscript were received by any of the authors.

© 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Kaplan‐Meier curve for inhibitor development. Kaplan‐Meier curves for inhibitor development in PUPs from a clinical study (broken line) and from a registry‐based study (solid line). The table below indicates patients numbers with inhibitor development and the patient numbers on treatment at the corresponding exposure days. Patients not followed up to 50 exposure days are right censored.

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