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.