Product information and disease description Place of product in therapy Disease description

Natural history, survival, and mortality

12 evidence topics · 8 sources

Onset in childhood and cumulative disability

“Most children with FOP develop episodic, painful, inflammatory soft tissue swellings called flare-ups during the first decade of life. While some flare-ups regress spontaneously, most transform soft connective tissues into mature heterotopic bone through a process of endochondral ossification.” (opens the source at this quote in a new tab)
“Most patients with FOP are confined to a wheelchair by the third decade of life and require lifelong assistance with activities of daily living. The median estimated life expectancy is 56 yr. Death often results from complications of thoracic insufficiency syndrome.” (opens the source at this quote in a new tab)

Prospective 36-month natural history study: flare-ups and new heterotopic ossification

“In total, 114 individuals participated; 33 completed the study (mean follow up: 26.8 months). Median age was 15.0 (range: 4-56) years; 54.4% were male. During the study, 82 (71.9%) individuals reported 229 flare-ups (upper back: 17.9%, hip: 14.8%, shoulder: 10.9%).” (opens the source at this quote in a new tab)
“Results from individuals receiving standard care for up to 3 years in this natural history study show the debilitating effect and progressive nature of FOP cross-sectionally and longitudinally, with greatest progression during childhood and early adulthood.” (opens the source at this quote in a new tab)

Imaged flare-ups with new heterotopic ossification at Day 84

“HO was present at the flare-up site in 71.2% of imaged flare-ups at flare-up Day 1, and 26.9% had new HO at flare-up Day 84 (Figure 1A).” (opens the source at this quote in a new tab)

Imaged flare-up frequency by age group

“A total of 52 flare-ups in 40 (35.1%) individuals were imaged (Supplement 2A). The proportion of individuals with ≥1 imaged flare-up was highest in the 2 to <8 years age group (47.1%) and lowest in the 25 to 65 years age group (25.9%).” (opens the source at this quote in a new tab)

Functional and physical function scores over 36 months

“At baseline, mean CAJIS total score was 11.8 (SD = 7.0) points and mean FOP-PFQ percentage of the worst total score was 46.3% (SD = 28.1%); small increases were observed from baseline to Month 36 (1.6 points and 7.3%, respectively; Supplement 3A and B).” (opens the source at this quote in a new tab)

One death during the 36-month natural history study

“One death occurred during the study: a 38-year-old female individual had fatal cardiac arrest not due to study procedures.” (opens the source at this quote in a new tab)

Baseline cross-sectional phenotype: HO volume and function increase with age

“Findings from 114 subjects (age range 4 to 56 years) were evaluated. While subject age was significantly (p < 0.0001) correlated with increased CAJIS (r = 0.66) and FOP-PFQ scores (r = 0.41), the estimated mean increases per year (based on cross-sectional average changes over time) were small (0.47 units and 1.2%, respectively). There was also a significant (p < 0.0001) correlation between baseline age and HO volume (r = 0.56), with an estimated mean increase of 25,574 mm3/year.” (opens the source at this quote in a new tab)

Anatomic progression and progression without flare-ups

“Onset of FOP usually occurred first in the neck and upper back, and with the exception of the jaw, progressed from axial to appendicular regions (Figure 1).” (opens the source at this quote in a new tab)
“Most body regions were affected before the third decade of life (Figure 2c).” (opens the source at this quote in a new tab)
“Almost half of all patients (46.9%; 230/490) reported disease progression without flare-up symptoms.” (opens the source at this quote in a new tab)

Clinical staging

“Based on assessment of FOP features in seven areas, it is possible to assign five clinical stages.” (opens the source at this quote in a new tab)
“Assessments of these features assign an individual with FOP to early/mild, moderate, severe, profound, or late-stage disease.” (opens the source at this quote in a new tab)

Median lifespan and causes of death in the international FOP community

“Sixty deaths (thirty male and thirty female patients) were reported in the fibrodysplasia ossificans progressiva community during a thirty-three-year-period. For all sixty patients, the median age at the time of death was forty years (range, three to seventy-seven years).” (opens the source at this quote in a new tab)
“The median lifespan estimated from the 371 individuals in the international fibrodysplasia ossificans progressiva community who were alive and the sixty who had died was fifty-six years (95% confidence interval, fifty-one to sixty years). The most common causes of death in patients with fibrodysplasia ossificans progressiva were cardiorespiratory failure from thoracic insufficiency syndrome (54%; median age, forty-two years) and pneumonia (15%; median age, forty years).” (opens the source at this quote in a new tab)

Survival compared with matched controls in France

“Overall survival was significantly worse in individuals with FOP vs the control group (p < .0001; Figure 4). Seven deaths were reported in the 77 individuals with FOP, and 8 deaths were reported in the 769 individuals without FOP. The mean (SD) age at death for individuals with FOP and controls was 50.4 (20.9) yr and 63.1 (18.3) yr, respectively (p = .2239).” (opens the source at this quote in a new tab)

Systematic review of reported mortality

“Ten of the 32 publications reported the number of deaths within the study cohorts” (opens the source at this quote in a new tab)
“However, none of the studies calculated annual mortality rates or contextualized the number of deaths observed.” (opens the source at this quote in a new tab)
“The most frequently reported causes of death, as determined by the investigators’ medical records review, were cardiovascular or cardiorespiratory issues, pneumonia, and trauma resulting from a fall.” (opens the source at this quote in a new tab)