A new treatment approach to fibrodysplasia ossificans progressiva patients - the canakinumab experience
2Sackler Faculty of Medicine, Tel Aviv University
3Division of Rheumatology, Bambino Gesù Children’s Hospital IRCCS
4Pediatric Orthopedic Department, Dana Children`s Hospital, Tel Aviv Medical Center
Background: Fibrodysplasia ossificans progressiva (FOP), is the most catastrophic form of heterotopic ossification (HO), due to an ongoing intracellular signaling through the bone morphogenic protein pathway. Unfortunately, there is no effective prophylactic treatment to change the course of this disease.
The recurrent paroxysmal appearance of inflammatory "lumps", and the fact that macrophages derived from FOP patients are in a pro-inflammatory state, as reported before, hint that FOP "behaves" as an auto-inflammatory disease.
Moreover, interleukin 1 (IL1) has been linked to the mineralization of human and mice bone marrow mesenchymal cells before.
Objectives: To lower the rate of FOP flares, and limit the symptoms and residual lesions, by using the anti- IL1beta agent canakinumab.
Methods: Patients` data were analyzed, to characterize the efficacy of canakinumab in ameliorating the progression of FOP
Results: Three FOP patients are currently treated with canakinumab 4mg/kg/month, with a total experience of over 4 patient years.
Markedly lowered rate of HO flares was documented:
* once monthly (vs. 3-4/month) in the male patient.
* almost none (vs. once monthly) in both female patients.
In general, no new HO sites were documented, but existing HO sites may kept growing under treatment, although growth rate was much lower, and response to corticosteroids was better (less doses were needed). Some of the cartilaginous lumps were diminished under canakinumab alone.
Conclusion: Our data may suggest that FOP flares are mediated by - IL1beta. Anti-IL-1 agents may have a role in ameliorating the progression of FOP. FOP may be an auto-inflammatory disease.