Intermittent and Short‐Term Empirical Ruxolitinib Regimen for Steroid‐Refractory Flareups of Fibrodysplasia Ossificans Progressiva

Fibrodysplasia ossificans progressiva (FOP) is an ultra‐rare genetic disorder with inflammation‐related flare‐ups resulting in catastrophic heterotopic ossification (HO). Janus‐associated kinase (JAK) inhibitors may have had a blocking effect on bone formation in controlling FOP flare‐ups by blocking multiple inflammatory signaling pathways. Continuous JAK inhibitor tofacitinib treatment has shown preliminary safety and effect in preventing FOP flare‐ups. There is concern that the use of long‐term continuous JAK inhibitors might cause renal, hepatic, and hematological toxicity, as well as increased infections and cancers. We incorporated a six‐week ruxolitinib (another JAK inhibitor) regimen given intermittently for empirical use at the flare‐up onset in a teenager after she experienced three consecutive corticosteroid‐refractory severe lower limb FOP flare‐ups within 1 year. The regimen proved well‐tolerated with efficacy in terms of blocking morbidity‐generating heterotopic ossification and extending the flare‐up‐free intervals to 5, 12, and 36 months until subsequent flare‐ups, respectively, accompanied by a stable cumulative analog joint involvement scale (CAJIS) score for the subsequent 5 years. The regimen appeared to inhibit new bone formation and may avoid long‐term use‐related toxicities in FOP patients.