Abstract Objective Exertional leg pain (ELP) is a distinctive musculoskeletal manifestation of familial Mediterranean fever (FMF), associated with severe disease and chronic inflammation. Despite adequate control of disease activity with colchicine, ELP often persists and contributes to disability, creating a serious unmet therapeutic need. This exploratory study evaluated the efficacy of IL-1 blockers in alleviating ELP in colchicine-resistant FMF (CR-FMF) patients. Methods Twenty-seven CR-FMF patients treated with IL-1 blockers (23 canakinumab, 4 anakinra) at the Sheba Medical Center FMF clinic were included. Patients retrospectively assessed ELP severity and quality of life (QOL), using a 0—10 visual analogue scale (VAS), before and during IL-1 blocker treatment. The primary end point was reduction in ELP severity, measured by change in VAS pain score. Results The cohort exhibited a severe phenotype (mean pre-treatment annual attack rate 50.69 ± 35.4; 55.5% M694V homozygous; 11% with amyloidosis). Following IL-1 blockade, 52% (14/27) of patients reported improvement in ELP. Mean pain scores decreased by 3.0 ± 3.68 points (p= 0.0003), and QOL scores improved by 3.07 ± 3.73 points (p= 0.0002). Residual ELP severity correlated strongly and negatively with QOL under biological treatment (r = –0.73, p 0.0001) Conclusion IL-1 blockers provide meaningful benefit in approximately half of patients with FMF-related ELP, supporting their role as a therapeutic option for this refractory manifestation. However, the persistence of ELP in a substantial proportion of patients underscores the need for additional therapeutic strategies to address this disabling manifestation.
Druyan et al. (Tue,) studied this question.