OBJECTIVES: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely debilitating genetic disorder characterised by congenital skeletal malformations and irreversible heterotopic ossification in soft and connective tissues. This review identified clinical, humanistic, and economic published literature to elucidate the burden of illness associated with FOP.

METHODS: Searches were conducted in MEDLINE, Embase, and Cochrane (inception to 09-Jun-2022); related conferences were manually searched. Dual screening, data extraction, and qualitative analysis were conducted.

RESULTS: From 1,429 abstracts identified, 53 publications were included; most reported clinical data (42/53), however humanistic (5/53) and economic (11/53) data were also identified. Information was primarily derived from three relatively new sources that have collated data from large numbers of patients with FOP: the FOP Natural History Study (NCT02322255), the FOP Registry (~34% of known FOP population internationally [2019]), and the FOP International Burden of Illness Survey (NCT04665323). According to the literature, FOP is progressive, with the neck and upper back earliest affected (at age 8.5 and 9.5 years, respectively) and wrists and feet affected later in life (54.5 and 58.5 years). Over 12 months, 48% of patients reported >1 flare-up frequently characterised by swelling, pain, and decreased movement. A significant relationship between decreased mobility and lower EQ-5D-5L scores has been reported; mean scores were 0.05 among patients with the most severe mobility restrictions. Within 12 months, 86% of patients with FOP required ≥1 physician visit and 27% were hospitalised. In older age groups, there was increased use of assistive devices and number of hospitalizations, which limited patients’ ability to attend school and become employed; 67% of patients did not have a paid occupation. Most patients required a caregiver, with the impact primarily falling to patients’ direct relatives.

CONCLUSIONS: Recent studies have increased understanding of FOP particularly related to the clinical and humanistic impact; however, evidence gaps related to the economic burden remain.