A paper published in the journal Haemophilia, suggests that clinical expectations for people with hemophilia have remained relatively static for years, falling out of alignment with treatment in the 21st century and its promise of unprecedented health outcomes.
The menu of products to treat a person with hemophilia (PwH) has grown dramatically in the last several decades, as breakthroughs in research and development continue to yield novel therapies that offer both improved protection from bleeds and greater ease of administration. In 2020, innovation has made possible the realization that patients may achieve vastly enhanced outcomes, even a “functional cure” of normal hemostasis.
Unfortunately, many current prophylaxis protocols for hemophilia A are still designed to maintain very modest factor VIII (FVIII) levels of more than 1%, a conservative goal that places patients in the mild-to- moderate category. The authors posit that this represents an antiquated model, a product of a very different time when therapies were less effective and supply limitations of plasma-based treatments weighed heavily on treatment protocols. While achievement of FVIII >1% at one time signified a historic improvement, resulting in improved outcomes, it still leaves patients at risk for bleeds.
“Aspirations for better treatment up to this point in time have been stymied by economic considerations and a failure of imagination. Payers, clinicians and in many cases PwH themselves have been satisfied with very slow incremental improvement in access to treatment, explain the authors. “The objective of a 1% trough level using prophylaxis has been seen as the holy grail for far too long. With newer treatments, novel products and gene therapy on the horizon, we must set our sights at a more ambitious goal—normal haemostasis and normal and optimized Quality of Life,” assert the authors.
Therefore, an updated model became necessary, one with patient outcomes that would be equivalent to other disease groups: to restore functioning to normal level comparable to the general population. A new approach first began to take shape in 2017 via an initial in person meeting of experienced clinicians and patients who concluded that a new model should align with the current treatment landscape and anticipate emerging, novel therapies. Through two subsequent global workshops in 2018 and 2019, healthcare providers and patient representatives from 24 countries developed a new treatment model. It was designed in a way that allows patients to reach a series of delineated milestones in a progressive fashion with the penultimate goal of health equity, defined by the World Health Organization as the “absence of avoidable or remediable differences among groups of people.”
“Prolongation of life is admirable but without optimizing therapy, patients are living longer lives with chronic pain and disability. Recent advancements that could normalize hemostasis open up the possibility of attaining a lifestyle unimpaired by disease complications,” explained the authors “Overcoming this challenge requires that PwH and physicians align their aspirations to achieve equity in their health and healthcare goals, respectively.”
The stepwise model includes specific, parallel clinical/patient-relevant outcomes, developed in ascending order so that each successive milestone represents an improvement on the previous, with the end goal of normal hemostasis and a lifestyle unburdened by hemophilia-related bleeding complications. Each milestone also encompasses their current status, as described by the authors, within the existing treatment landscape.
Milestone 1. Survival/prevent premature death – Achievable with use of factor concentrates and home treatment/easy access to health care.
Milestone 2. Minimal joint impairment/improved quality of life, participation in activities of daily living – Achievable in virtually all patients with prophylaxis started early in life.
Milestone 3. Freedom from spontaneous bleeds/ability to engage in low‐risk activities – Achievable in most patients with current prophylactic regimens.
Milestone 4. Attain ‘normal’ mobility/participation in work, school and family life without restriction – Achievable in some patients with prophylaxis but must be initiated at an early age.
Milestone 5. Able to sustain minor trauma/more unrestricted lifestyle – Current management is on-demand replacement factor and other treatments to manage bleeds.
Milestone 6. Undergo surgery or major trauma without additional intervention/not dependent on specialized health care – Managed in consultation with hemophilia treatment center and with laboratory support that can monitor, and supply required replacement factor levels.
Milestone 7. Normal hemostasis/optimized health and well‐being – Would require treatment (prophylaxis, gene therapy or non-replacement factor therapy) almost immediately after birth, while avoiding immune tolerance/inhibitors; promising gene therapy trials.
The workshop participants conceived of this stepwise approach for broad applicability and utility, so that regardless of an individual’s unique situation or their nation’s health system, a person may find their spot on the milestones staircase. Such a model could be utilized as an important advocacy tool by providing both guidance and context for the various stakeholders in the international hemophilia community including, clinicians, patients, health systems, payers, and others.
“This new treatment paradigm encompasses a shared vision by providers and patients alike, tracking clinical and patient‐centric outcomes in parallel, such that value is not limited to efficacy endpoints alone, but rather provides a clear path towards normal haemostasis,” concluded the authors.
Skinner M, Nugent D, Wilton P, et al. Achieving the Unimaginable: Health Equity in Haemophilia. Haemophilia. 2020 January; 26(1): 17-24.