Contemporary approaches to treat people with hemophilia: what's new and what's not?

Abstract

The care of people with hemophilia with access to treatment has evolved over the past 70 years, with an average life expectancy like unaffected peers. For people with hemophilia living in low- and middle-income countries, the same is not true because of the lack of access to diagnosis and treatment. It is imperative to close gaps in care that exist throughout the world. Here, we provide a narrative review of hemophilia and the treatments available to people with hemophilia A and B with the goal of achieving a hemophilia-free state. We aim to provide information on what is new and what gaps remain that preclude equitable outcomes for everyone with hemophilia. Information on the current state of hemophilia care and outcomes, the products available for the treatment of people with hemophilia, comprehensive interdisciplinary care of people with hemophilia, and the remaining gaps in care for people with hemophilia were assembled by the authors using relevant literature. Research must focus on preventing all bleeding, and new approaches to detect joint bleeding are needed. Training on and implementation of comprehensive interdisciplinary care is needed to elevate the standards of care in low- and middle-income countries. The development and introduction of improved factor replacement and nonfactor products, such as second-generation bispecific monoclonal antibodies and targeted inhibitors of the anticoagulant mechanisms along with genetic therapies, have the possibility of normalizing hemostasis and achieving health equity for people with hemophilia. Improved outcomes and, ultimately, health equity, can only be realized if diagnosis, education, and care are accessible to everyone living with hemophilia worldwide.

Keywords: health equity; hemophilia; novel therapies; prophylaxis; psychosocial; quality of life; shared decision-making.

Figure

Five categories of therapeutics are available in the clinic or are in development to treat people with hemophilia, including standard half-life and extended half-life (EHL) factor (F)VIII and FIX replacement products, nonfactor therapies, and gene therapy for hemophilia A and B. The pharmacokinetic profiles of standard half-life and EHL products, along with their characteristic peaks and troughs of factor levels (red) and hemostatic effect (blue), are shown in the lower and upper profiles. Trough FVIII or FIX levels have historically been targeted to be above 1 IU/dL (1%), but effective prophylaxis and suppression of bleeding likely only is achieved when the trough level is maintained at substantially higher (>10%-15%) levels. The attainment of hemostasis in the nonhemophilic range is currently only achievable following successful gene therapy. The uncertain durability of hemophilia A gene therapy is shown by the parabolic curve, while that of hemophilia B gene therapy appears to be stable and durable. The frequency of intravenous infusions (blue) and subcutaneous injections (red) of the products is shown under the lower profile by the up arrows (), and the one-time infusion of a gene therapy product is shown by an open circle ().