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- Title
Long-term use of interleukin-1 inhibitors reduce flare activity in patients with fibrodysplasia ossificans progressiva.
- Authors
Haviv, Ruby; Zeitlin, Leonid; Moshe, Veronica; Ziv, Amit; Rabinowicz, Noa; Benedetti, Fabrizio De; Prencipe, Giusi; Matteo, Valentina; Cunto, Carmen Laura De; Hsiao, Edward C; Uziel, Yosef
- Abstract
Objectives 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 IL-1β. This study describes the short- and long-term responses of FOP patients to anti-IL-1 therapy. Methods 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 centres. Results 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 a 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. Conclusion 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 the formation of new HO. Funding 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.
- Subjects
FIBRODYSPLASIA ossificans progressiva; DISEASE exacerbation; RESEARCH funding; HEALTH status indicators; VISUAL analog scale; QUESTIONNAIRES; TREATMENT duration; TREATMENT effectiveness; BLOOD plasma; PAIN; RESEARCH; CASE studies; DISEASE relapse; HEALTH outcome assessment; INTERLEUKIN-1; GLUCOCORTICOIDS; INTERLEUKINS; WELL-being; CHEMICAL inhibitors
- Publication
Rheumatology, 2024, Vol 63, Issue 9, p2597
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/keae255