%0 Journal Article
%T Long term use of interleukin-1 inhibitors reduce flare activity in patients with fibrodysplasia ossificans progressiva.
%A Haviv R
%A Zeitlin L
%A Moshe V
%A Ziv A
%A Rabinowicz N
%A De Benedetti F
%A Prencipe G
%A Matteo V
%A De Cunto CL
%A Hsiao EC
%A Uziel Y
%J Rheumatology (Oxford)
%V 0
%N 0
%D 2024 May 11
%M 38733591
%F 7.046
%R 10.1093/rheumatology/keae255
%X <B>OBJECTIVE: </B>Fibrodysplasia ossificans progressiva (FOP) is one of the most catastrophic forms of genetic heterotopic ossification (HO). FOP is characterized by severe, progressive inflammatory flare-ups, that often lead to HO. The flare-ups are associated with increased inflammatory cytokine production, suggesting auto-inflammatory features driven by interleukin-1β (IL-1β). This study describes the short- and long-term responses of FOP patients to anti-IL-1 therapy.<BR><B>METHODS: </B>Previously, we reported that a patient with FOP treated with anti-IL-1 agents showed dramatically lower rates of flare-ups, improved flare-up symptoms, decreased use of glucocorticoids, and apparently decreased size of residual lesions. Plasma analyses also showed marked elevation in IL-1β levels during a FOP flare, further supporting a role of IL-1β in the pathogenesis of FOP flares. Here, we report results from long-term therapy with IL-1 inhibitors in that patient, and describe 3 additional patients, from two medical centers.<BR><B>RESULTS: </B>All 4 patients showed persistent improvement in flare activity during treatment with IL-1 inhibitors, with minimal formation of new HO sites. Two patients who stopped therapy experienced resurgence of flare activity that was re-suppressed upon re-initiation. These patients had IL-1β levels comparable to those in IL-1β-driven diseases. Child Health Assessment Questionnaires confirmed extensive subjective improvements in the pain and general health visual analogue scales.<BR><B>CONCLUSIONS: </B>This case series demonstrates significant benefits from IL-1 inhibitors for reducing flare activity and improving the general health of patients with FOP. These data provide strong support for additional studies to better understand the function of IL-1 inhibition, primarily in reducing formation new HO.<BR><B>BACKGROUND: </B>RH received support from the International FOP Association ACT grant; ECH received support from NIH/NIAMS R01AR073015 and the UCSF Robert Kroc Chair in Connective Tissue and Rheumatic Diseases III.