Evaluation of safety and effectiveness of factor VIII treatment in haemophilia A patients with low titre inhibitors or a personal history of inhibitor

Vadim Romanov; Maura Marcucci; Ji Cheng; Lehana Thabane; Alfonso Iorio

doi:10.1160/TH14-10-0882

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2015; 114(01): 56-64
DOI: 10.1160/TH14-10-0882

Coagulation and Fibrinolysis

Schattauer GmbH

Evaluation of safety and effectiveness of factor VIII treatment in haemophilia A patients with low titre inhibitors or a personal history of inhibitor

Patient Data Meta-analysis of rAFH-PFM Post-Authorization Safety Studies

Vadim Romanov

¹Baxter HealthCare, Global Medical Affairs, Westlake Village, California, USA

,

Maura Marcucci

²UMI, Milan, Italy

,

Ji Cheng

³St Joseph’s Hospital, Hamilton, Ontario, Canada

⁴Department of Clinical Epidemiology and Biostatistics, McMaster, University, Hamilton, Ontario, Canada

,

Lehana Thabane

³St Joseph’s Hospital, Hamilton, Ontario, Canada

⁴Department of Clinical Epidemiology and Biostatistics, McMaster, University, Hamilton, Ontario, Canada

,

Alfonso Iorio

⁴Department of Clinical Epidemiology and Biostatistics, McMaster, University, Hamilton, Ontario, Canada

⁵Department of Medicine, McMaster, University, Hamilton, Ontario, Canada

› Institutsangaben

Abstract

Summary

There is no prospective evidence on inhibitor recurrence among haemophilia A patients with low titre inhibitors or history of inhibitors, and whether or how therapeutic choices affect the risk of recurrence. The aims of this study were to synthesise safety data in patients with moderate-severe haemophilia A and with low titre inhibitors or inhibitor history enrolled in the rAHF PFM (ADVATE) – Post-Authorization Safety Studies (ADVATE-PASS) international programme. The study was conducted in clinics participating to the ADVATE PASS programme. The patient population consisted of patients entering the studies with low titre (≤5 BU) inhibitors or a positive personal history of inhibitors. Patients on Immune Tolerance Induction at study entry were excluded. Primary outcome was new or recurrent inhibitor titre > 5 BU. Secondary outcomes were any increase of inhibitor titre not reaching 5 BU; any unexplained change in treatment regimen. Primary analysis was done by two-stage random effects meta-analysis. Secondary analysis was done by a hierarchical Bayesian random effects logistic model. A total of 219 patients from seven studies were included. Of these 214 (97.7 %) patients had been previously treated for more than 50 exposure days. Two hundred ten patients had positive history for inhibitors, nine a baseline measurable titre. No patient presented a primary outcome event (95 % confidence interval [CI] 0–1.6 %). Six patients with previous history developed a low titre recurrence (overall rate 2.2, 95 %CI 0–4.8 %). When any increase of inhibitor titre or any treatment change was accounted for, overall 3.7 % (95 % CI 0 %-8.0 %) of patients experienced the outcome. In conclusion, the observed rate of events does not support the definition of this population as at high risk for inhibitor development.

Keywords

Haemophilia A - ADVATE - low titre inhibitors - PASS - switching

Volltext

Referenzen

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