| 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; De Benedetti, Fabrizio; Prencipe, Giusi; Matteo, Valentina; De Cunto, Carmen Laura; Hsiao, Edward C; Uziel, Yosef |
| Contributors: |
International FOP Association ACT; NIH; NIAMS; UCSF Robert Kroc Chair in Connective Tissue and Rheumatic Diseases III |
| Source: |
Rheumatology ; volume 63, issue 9, page 2597-2604 ; ISSN 1462-0324 1462-0332 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2024 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/rheumatology/keae255 |
| DOI: |
10.1093/rheumatology/keae255/57824540/keae255.pdf |
| Availability: |
https://doi.org/10.1093/rheumatology/keae255; https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/keae255/57824540/keae255.pdf; https://academic.oup.com/rheumatology/article-pdf/63/9/2597/59007301/keae255.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.D2A74827 |
| Database: |
BASE |