Inhibitors: solving the problem

Three experts on inhibitors in hemophilia opened the first session of the 10th World Federation of Hemophilia (WFH) Global Forum held in Montreal on November 9, 2017. The session, Inhibitors—solving the problem, was chaired by Marijke van den Berg, MD, PhD.

Inhibitors—defining the problem

David Lillicrap, MD, a researcher from the Clinical and Molecular Hemostasis Research Group, Queen’s University, Kingston, Canada, gave a brief overview of inhibitor epidemiology and management. Lillicrap reminded the audience that the management of people with hemophilia and inhibitors has changed very little since the discovery of inhibitors over 50 years ago. He added that even less has been done to prevent the occurrence of inhibitors. Nonetheless, Lillicrap identified several opportunities to advance inhibitor prevention and management, including:

  1. Improving laboratory monitoring of the factor VIII (FVIII) immune response, especially during early exposure to FVIII
  2. Designing clinical trials to assess the risk of inhibitor development by product type
  3. Introducing novel non-replacement therapies for people with inhibitors to improve therapeutic efficacy and quality of life

Call to action—coordinated prevention in previously untreated patients (PUPs) and intervention in patients with inhibitors

Steven Pipe, MD, is a pediatric hematologist/oncologist from the University of Michigan Hospitals and Health Centers, U.S.A., and chair of the National Hemophilia Foundation’s (NHF) Medical and Scientific Advisory Council (MASAC). Pipe presented the U.S.A.-focused priorities of MASAC’s Inhibitor Prevention and Eradication Working Group: to progressively reduce the rate and burden of inhibitors within the U.S.A. hemophilia population and to provide ongoing surveillance. Pipe explained that these priorities would be achieved by:

  1. Increasing enrollment in the national inhibitor surveillance program
  2. Optimizing laboratory assays and monitoring
  3. Developing a coordinated scientific agenda
  4. Prioritizing the implementation of interventions to reduce inhibitor development and more effectively eradicate inhibitors

Comparison of hemophilia A PUP data derived from historic clinical PUP studies and from the PedNet registry

Christine Keipert, PhD, is a scientist from the Paul-Ehrlich-Institut, Langen, Germany. She presented a comparison of 20 years of clinical trial data with 16 years of data from the European PEDiatric NETwork (PedNet) registry for hemophilia management. Keipert explained that there were no major differences in the characteristics of hemophilia A PUPs between the clinical trials and PedNet. Indeed, the two data sources were complementary, and a well-managed patient registry appears to be as good as clinical trials for detecting inhibitor development. Keipert closed the first session by concluding that the data required for PUPs can be fulfilled in registries; however, there needs to be agreement on a minimum data set that should be collected, and on rules for data sharing.