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. 2021 Aug 5;16(1):350.
doi: 10.1186/s13023-021-01983-2.

Prevalence of fibrodysplasia ossificans progressiva (FOP) in the United States: estimate from three treatment centers and a patient organization

Robert J Pignolo  1 , Edward C Hsiao  2   3   4 , Genevieve Baujat  5 , David Lapidus  6 , Adam Sherman  7 , Frederick S Kaplan  8   9
Affiliations

Prevalence of fibrodysplasia ossificans progressiva (FOP) in the United States: estimate from three treatment centers and a patient organization

Robert J Pignolo et al. Orphanet J Rare Dis. .

Abstract

Background: Fibrodysplasia ossificans progressiva (FOP), an ultra-rare, progressive, and permanently disabling disorder of extraskeletal ossification, is characterized by episodic and painful flare-ups and irreversible heterotopic ossification in muscles, tendons, and ligaments. Prevalence estimates have been hindered by the rarity of FOP and the heterogeneity of disease presentation. This study aimed to provide a baseline prevalence of FOP in the United States, based on contact with one of 3 leading treatment centers for FOP (University of Pennsylvania, Mayo Clinic, or University of California San Francisco), the International Fibrodysplasia Ossificans Progressiva Association (IFOPA) membership list, or the IFOPA FOP Registry through July 22, 2020.

Results: Patient records were reviewed, collected, and deduplicated using first and last name initials, sex, state, and year of birth. A Kaplan-Meier survival curve was applied to each individual patient to estimate the probability that he or she was still alive, and a probability-weighted net prevalence estimate was calculated. After deduplication, 373 unique patients were identified in the United States, 294 of whom who were not listed as deceased in any list. The average time since last contact for 284 patients was 1.5 years. Based on the application of the survival probability, it is estimated that 279 of these patients were alive on the prevalence date (22 July 2020). An adjusted prevalence of 0.88 per million US residents was calculated using either an average survival rate estimate of 98.4% or a conservative survival rate estimate of 92.3% (based on the Kaplan-Meier survival curve from a previous study) and the US Census 2020 estimate of 329,992,681 on prevalence day.

Conclusions: This study suggests that the prevalence of FOP is higher than the often-cited value of 0.5 per million. Even so, because inclusion in this study was contingent upon treatment by the authors, IFOPA membership with confirmed clinical diagnosis, and the FOP Registry, the prevalence of FOP in the US may be higher than that identified here. Thus, it is imperative that efforts be made to identify and provide expert care for patients with this ultra-rare, significantly debilitating disease.

Keywords: ACVR1; Epidemiology; FOP; Fibrodysplasia ossificans progressiva; Heterotopic ossification; Prevalence; Rare disease.

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Conflict of interest statement

None of the authors have competing interests to report. Robert J. Pignolo: Research investigator: Clementia/Ipsen, Regeneron; Advisory board: President of the International Clinical Council on FOP. Edward C. Hsiao: Research Investigator, Clementia/Ipsen; Prior research support from Regeneron. And Neurocrine Biosciences. Volunteer service on the IFOPA Medical Registry Advisory Board, the Fibrous Dysplasia Foundation Medical Advisory Board, and the International Clinical Council (ICC) of FOP. Genevieve Baujat: Research Investigator Ipsen, Regeneron, member of the International Clinical Council (ICC) of FOP, European Council for FOP and FOP France Medical Advisory Board. David Lapidus: David Ladipus was paid as a consultant by IFOPA for his work in compiling data. Prior consultant for Clementia (role ended in September, 2019). Adam Sherman: None. Frederick S. Kaplan: Research investigator: Ipsen & Regeneron; IFOPA Medical Advisory Board; Founder and Immediate Past-President of the International Clinical Council (ICC) on FOP; Chair of the Publications Committee of the ICC.

Figures

Fig. 1
Fig. 1
Waterfall of United States FOP patient population estimate on 22 July 2020. A pooled total of 720 patients were identified based on the 3 sources (the IFOPA membership list and FOP Registry were considered together as one source). Following deduplication based on first/last initial, sex, date of birth, and location, 373 unique patients were identified. Of these patients, 294 had not been reported to be deceased. Ten patients without sufficient data (year of birth, date of last contact) to calculate the survival-weighted prevalence were removed. After application of a survival prediction based on patient age at last contact and time since last contact (prevalence date of 22 July 2020), an unadjusted prevalence of 0.85 per million was calculated. After adjusting using a conservative survival rate (92.3%) based on the bottom quintile of the average estimated survival rate reported by Kaplan 2010 [2], an adjusted prevalence of 0.88 per million was calculated. When instead adjusting using the average survival rate of 98.4% reported by Kaplan 2010 [2], the adjusted prevalence is 0.88 per million
Fig. 2
Fig. 2
Overview of Patient Demographics. A Age distribution of 285 subjects with age data. B Time since last contact of 285 subjects with time since last contact data
Fig. 3
Fig. 3
Patient identification overlap. The Venn diagram shows the number of the 373 unique patients identified based on source (IFOPA membership list, FOP Registry, and any of the 3 centers). The term “source” refers to the IFOPA membership list, the FOP Registry, and each of the 3 centers represented by FOP expert clinicians
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References

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