Current challenges and opportunities in the care of patients with fibrodysplasia ossificans progressiva (FOP): an international, multi-stakeholder perspective

Abstract

Background Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, disabling genetic disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification of soft and connective tissues. Assiduous attention to the unmet needs of this patient community is crucial to prevent potential iatrogenic harm and optimize care for individuals with FOP. Objective To gather international expert opinion and real-world experience on the key challenges for individuals with FOP and their families, highlight critical gaps in care, communication, and research, and provide recommendations for improvement. Methods An international group of expert clinicians, patients and patient advocates, caregivers and representatives from the international FOP community participated in a virtual, half-day meeting on 22 March 2021 to discuss the key unmet needs of individuals with FOP. Results Individuals with FOP often face the frustration of long diagnostic journeys, the burden of self-advocacy and the navigation of novel care pathways. Globally, patients with FOP are also confronted with inequities in access to diagnosis and specialist care, and consequently, unequal access to registries, clinical trials, and essential support from patient associations. Organizations such as the International FOP Association, the International Clinical Council on FOP, and national FOP organizations work to provide information, facilitate access to expert clinical guidance, nurture patient empowerment, fund FOP research and/or foster meaningful collaborations with the research community. The non-profit Tin Soldiers Global FOP Patient Search program aims to identify and provide a pathway to diagnosis and care for individuals with FOP, particularly in underserved communities. Such global initiatives and the increasingly widespread use of telemedicine and digital platforms offer opportunities to improve vital access to care and research. Conclusions This multi-stakeholder perspective highlights some of the unmet needs of individuals with FOP and their families. Regional and international organizations play an important role in improving the quality of life of those they reach in the global FOP community. However, globally, fundamental issues remain around raising awareness of FOP among healthcare professionals, identifying individuals with FOP, reducing time to diagnosis, and ensuring access to best practice in care, support, and clinical research. Medical writing support was industry-sponsored.

Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility

“…The International Clinical Council on FOP [22] recommends nonoperative treatment of fractures in patients with FOP, when possible, to avoid iatrogenic harm that could incite flareups and additional HO and avoid life-threatening complications owing to general anesthesia [10, 16]. Our study supports the notion of nonoperative treatment of fractures in FOP, when possible, because 97% of the fractures appeared to have healed without issue with a nonoperative approach.…”

“…However, HO was seen radiographically at all anatomic locations in which patients reported post-traumatic flareups and resultant loss of mobility. Importantly, loss of mobility after a traumatic flareup was almost always thought to be HO-related [21][22][23][24][25].…”

Novel Therapeutic Targets for Fibrodysplasia Ossificans Progressiva: Emerging Strategies and Future Directions

“…The limited understanding of the disease hinders the identification of precise targets for therapeutic intervention, and accurate animal models that faithfully replicate FOP characteristics are scarce [23]. The risk of exacerbating the condition poses difficulties in implementing therapeutic interventions such as surgery or drug treatments [24].…”

Navigating the Complex Landscape of Fibrodysplasia Ossificans Progressiva: From Current Paradigms to Therapeutic Frontiers

“…The structural and epistemological complexities in executing clinical trials for FOP, or any ultrarare disease, are enormous [36,118]. These obstacles include a dearth of standardized natural history data to inform trial designs, scarcity of validated and surrogate outcome measures, and diminutive patient populations, rendering traditional large-scale randomized control trials (RCTs) infeasible [36,118,119].…”