SUN-737 Relationship Between Whole-Body Heterotopic Ossification (HO) Volume, as a Proxy of Chest HO, and Pulmonary Function: A Post-Hoc Analysis of a Natural History Study (NHS) of Fibrodysplasia Ossificans Progressiva (FOP)

Abstract Disclosure: E. Hsiao: Ipsen, Clementia, Ultragenyx. J.R. Marden: Analysis Group Inc. A. Anderson: Analysis Group Inc. E. Pranschke: Analysis Group Inc. (at the time of this analysis and development of the abstract). P. Wright: Ipsen. N. Shamseddine: Ipsen. G. Su: None. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification (HO), abnormal bone formation in soft and connective tissues that is associated with disability and shortened life expectancy.1-3 While restriction of pulmonary function due to chest wall deformity is documented, data on the relationship between HO volume and pulmonary function are limited.4 This analysis used data from a natural history study (NHS; NCT02322255) to quantify the relationship between HO volume and pulmonary function among patients with FOP.5 Given a strong positive correlation between chest HO (defined as HO developed in the chest, neck, or shoulders) and whole-body HO in the NHS data (r=0.72, p<0.0001), whole-body HO volume (‘HO’, in 100,000 mm3) was used as a proxy for chest HO in this analysis. Pulmonary function was defined as the reduction of forced vital capacity percent-predicted (‘FVCpp’) below severe (<50%) and very severe (<30%) thresholds. The relationship between HO and FVCpp was assessed cross-sectionally via unadjusted and adjusted logistic regression models with an exchangeable correlation structure, accounting for multiple observations per patient. All NHS visits with non-missing data on the following covariates were included: age, sex, presence of steroid use in the previous 12 months, and time since last flare-up. The models included 109 patients (male: 53.2%) with 248 visits (18 December 2014 - 11 April 2019). Across all visits, mean (standard deviation [SD]) age was 19.0 (9.7) years, mean (SD) time since last flare-up was 20.8 (32.9) months, and 50.8% of visits had steroid use in the past 12 months. In the unadjusted models, the odds of having FVCpp<50% were 1.15 times higher (95% confidence interval [CI]: 1.03-1.28; p=0.012) and the odds of having FVCpp<30% were 1.22 times higher (95% CI: 1.12-1.33; p<0.001) for every additional 100,000 mm3 of HO. When adjusting for covariates, the odds of having FVCpp<50% and FVCpp<30% were 1.09 times higher (95% CI: 0.97-1.24; p=0.159) and 1.12 times higher (95% CI: 1.00-1.25; p=0.047), respectively, for every additional 100,000 mm3 of HO. Results were similar but non-significant when adjusting for whether the last flare-up was in the chest region. These analyses may be underpowered to detect statistical significance if the true effect sizes are below 1.10; however, consistent effect sizes across models suggest that results remained robust to model changes. This analysis found that greater whole-body HO volume was associated with increased odds of very severe pulmonary function restriction, indicating the need to evaluate and prioritize strengthening pulmonary function in patients with FOP to potentially improve their life expectancy and quality of life. 1. Zhang et al. 2013. 2. Connor et al. 1982. 3. Kaplan et al. 2010. 4. Botman et al. 2021. 5. Pignolo et al. 2022. Funding: Ipsen. Presentation: Sunday, July 13, 2025