A Delphi Consensus Approach for Difficult-to-Treat Patients with Severe Hemophilia A without Inhibitors

Abstract

Introduction

Over the past decade, there has been an increase in novel therapeutic options to treat hemophilia A. It is still unclear how these novel treatments are used in the management of patients with hemophilia A, particularly those with challenging clinical scenarios who are typically excluded in clinical trials.

Purpose

This study aimed to understand the areas of consensus and disagreement among hematologists regarding the preferences toward therapeutic approaches for difficult-to-treat patients with severe hemophilia A without inhibitors.

Patients and Methods

During February–June 2020, a three-round modified Delphi study was conducted to generate consensus among 13 US experts in the field of hemophilia. Experts were asked about their preferences toward therapeutic options for patients with challenging clinical situations, including age-related morbidities (eg, myocardial infarction, joint arthropathy), increasing demand for high-impact physical activities, early onset osteoporosis, and newborns with hemophilia A. Consensus was defined as ≥75% agreement between the panelists.

Results

Consensus was reached on many, but not all cases, leaving uncertainty about appropriateness of therapeutic approaches for some patients where clinical evidence is not available or driven by physicians’ or patients’ preferences toward therapeutic options. A majority of panelists preferred FVIII replacement therapy rather than emicizumab prophylaxis for the challenging cases presented due to established evidence on safety, efficacy, and level of bleed protection for FVIII treatment.

Conclusion

Recommendations emerging from this study may help guide practicing hematologists in the management of challenging hemophilia A cases. Future studies are needed to address treatment options in the clinical cases where no consensus was reached.

Keywords:

• emicizumab
• expert elicitation
• FVIII
• treatment
• management

Ethics Approval

Using the Department of Health and Human Services regulations, 45 CFR 46.104(d)(2), Advarra Institutional Review Board (IRB) exempted this study from IRB oversight.

Disclosure

Sreenivas P. Veeranki was a former employee and Priti Pednekar, Marlon Graf, and Rifat Tuly are current employees of PRECISIONheor, a research consultancy to the health and life sciences industries. Sreenivas P. Veeranki is now affiliated with Optum LifeSciences, Eden Prairie, MN. Katharine Batt served as a consultant on this project through PRECISIONheor. Michael Recht’s institutions have received research funding from Bayer, BioMarin, CSL Behring, Genentech, Grifols, Hema Biologics, LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi, Spark, Takeda, and uniQure. He has served as a consultant to Catalyst Biosciences, CSL Behring, Genentech, Hema Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda, and uniQure. He serves on the Board of Directors for the Foundation for Women and Girls with Blood Disorders and Partners in Bleeding Disorders. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by Takeda Pharmaceutical Company Limited, however, the sponsor had no role in the study, which involved design, execution of the Delphi panel, and analysis of study findings.