Interleukin-1 Inhibitors - a New Hope for Fibrodysplasia Ossificans Progressiva?
2Sackler Faculty of Medicine, Tel Aviv University, ישראל
3Division of Endocrinology and Metabolism, University of California, ארצות הברית
4Pediatric Orthopedic Department, Dana-Dwek Children's Hospital, Sourasky Medical Center, ישראל
5Division of Rheumatology, Bambino Gesù Children’s Hospital IRCCS, איטליה
Background: Fibrodysplasia ossificans progressiva (FOP) is the most catastrophic form of heterotopic ossification (HO), due to ongoing intracellular signaling through the BMP pathway. It results in rapid and irreversible bone accumulation and loss of mobility. Unfortunately, there is no effective therapy to change the disease course.
The recurrent, paroxysmal appearance of inflammatory "lumps" and the fact that studies in FOP patients, and other forms of HO, indicate that several cytokines, including interleukin-1 (IL-1), are increased, indicate a similarity between FOP and other auto-inflammatory diseases. We hypothesized that anti-IL1 agents would ameliorate disease progression.
Objectives: To report our long-term experience using canakinumab (anti-IL1b) to prevent FOP flares.
Methods: Patients` data were analyzed to characterize the efficacy of canakinumab in ameliorating FOP progression.
Results: Four FOP patients are currently being treated with 4mg/kg/month canakinumab, with a total experience of over 7 patient years. Markedly lower rate of HO flares was documented, with a decrease from 1–3.1 to approximately 0.27 flares per month. In general, no new HO sites were documented, but existing sites may keep growing under treatment, although at a much slower rate. Response to corticosteroids was improved and some lumps diminished under canakinumab alone.
Conclusions: Our data suggest that FOP may be an auto-inflammatory disease and flares are mediated by IL1b. Anti-IL1 agents may have a role in ameliorating FOP progression, which offers new hope to FOP patients.