OBJECTIVES: To examine the relationships between an intermediate endpoint (heterotopic ossification [HO] volume) and functional and quality of life (QoL) outcomes in patients with FOP, an ultra-rare genetic disorder characterized by progressive, cumulative, and irreversible HO in soft and connective tissues.

METHODS: Data from 171 patients were extracted from the FOP Natural History Study (NCT02322255) and the MOVE phase III trial (NCT03312634) and used to analyze the relationships between HO and the Cumulative Analogue Joint Involvement Scale (CAJIS), the FOP-Physical Function Questionnaire (FOP-PFQ), and the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Scale. Summary scores distinguishing between the upper and lower extremities were used for HO, CAJIS, and FOP-PFQ. For HO, additional scores were used for the separate underlying body regions. Fixed and mixed effect models were fitted cross-sectionally and longitudinally.

RESULTS: Considering the cross-sectional data for the CAJIS scores, the highest Spearman correlations (>0.50) were obtained using the mixed effect models including the underlying body regions. Changes over time were best predicted using the overall extremity scores. The FOP-PFQ total and upper extremity scores were best predicted when including all HO and CAJIS extremity scores; the FOP-PFQ lower extremity score model was best predicted when including the HO and CAJIS lower extremity scores. In the models for PROMIS, HO in the arms and the lower extremity CAJIS score were found to be significant predictors (p<0.05; the latter only for PROMIS physical score). No significance was found predicting longitudinal changes in values.

CONCLUSIONS: Cross-sectional as well as longitudinal data confirm a logical significant relationship between HO regions and CAJIS and FOP-PFQ. There is insufficient data to confirm or reject a relationship between HO and PROMIS. These results help to better understand the relationships between HO and functional and QoL outcomes in FOP.