Ankylosing spondylitis (AS) is characterized by chronic inflammation of the axial skeleton, sacroiliac joints, and entheses, often presenting in early adulthood and its pathogenesis remains incompletely understood and appears to involve a complex interplay between autoinflammatory and autoimmune mechanisms 1, 2. Genetic susceptibility plays a central role in AS. Beyond the strong association with HLA-B27, several molecular pathways, including the IL-17/IL-23 axis, endoplasmic reticulum aminopeptidases (ERAP1/2), have been implicated in disease development 2. Variants of the MEFV gene, classically associated with Familial Mediterranean Fever (FMF), have also been linked to an increased frequency of spondyloarthritis in FMF patients and their relatives 3. In particular, the M694V mutation has been associated with heightened inflammatory activity and increased disease susceptibility 4. FMF is considered a prototype autoinflammatory disorder driven by innate immune dysregulation and excessive IL-1–mediated inflammation 5. Colchicine, the mainstay of FMF treatment, suppresses inflammation through inhibition of microtubule polymerization and downstream inflammasome activation 5. Despite overlapping inflammatory pathways between FMF and AS, colchicine has not been systematically evaluated as a treatment option for AS and has only been reported in isolated cases, such as AA amyloidosis secondary to AS 6. We included 28 patients with established diagnoses of AS and FMF. AS was diagnosed according to the 1984 Modified New York Criteria, and FMF diagnosis was based on the Tel-Hashomer criteria 4, 5. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Visual Analogue Scale (VAS) for back pain before and after colchicine treatment. Genetic data, including MEFV mutation status, and treatment histories were obtained from medical records. The mean age of the patients was 44.89 ± 10.9 years with disease duration of AS and FMF being 12.35 ± 6.95 years and 17.71 ± 7.72 years, respectively. Colchicine treatment was associated with improvement in both BASDAI (6.17 ± 2.56 to 5.05 ± 2.26, p = 0.068) and VAS back pain scores (6.69 ± 3.65 to 5.48 ± 2.65, p = 0.145) without reaching statistical significance. Similarly no significant improvement was observed in patients carrying heterozygous M694V mutations (n = 9) for either parameter. In contrast, patients with homozygous M694V mutation (n = 6), both BASDAI and VAS improvement was found significant (Table 1). Our findings suggest a genotype-specific response to colchicine in AS patients with coexisting FMF. AS is increasingly recognized as a disease with overlapping autoinflammatory and autoimmune features 2. Its classification as an MHC class I–opathy and the evidence linking inflammasome activation to enhanced MHC class I expression further support this concept 7. Colchicine inhibits NLRP3 inflammasome activation and IL-1 secretion, pathways that are central to FMF pathogenesis and may also contribute to AS, particularly in genetically susceptible individuals 8. Additionally, interactions between IL-1, TNF, and the IL-17/IL-23 axis may play a role in amplifying inflammation 9. IL-1–mediated suppression of IL-2 and FOXP3 expression may further impair regulatory T-cell function, providing a potential mechanistic link between autoinflammatory and autoimmune processes 10. The significant improvement observed exclusively in M694V homozygous patients suggests that effective control of FMF-related inflammation may also modulate AS disease activity in this subgroup. In contrast, the absence of benefit in heterozygous patients highlights the importance of genetic stratification. Previous studies evaluating IL-1 inhibitors in AS have reported inconsistent results, likely due to small sample sizes 11, 12. This study has limitations, including its retrospective design, reliance on patient recall for BASDAI and VAS scores, and potential confounding related to FMF disease activity. In addition, the number of patients included in this study needs to be increased in future, larger prospective studies. Nevertheless, it represents the first systematic evaluation of colchicine's effect on AS disease activity and identifies a clinically meaningful response in a genetically defined subgroup. Colchicine may reduce disease activity in AS patients carrying homozygous MEFV M694V mutations, suggesting a genotype-specific therapeutic effect and reinforcing the role of autoinflammatory mechanisms in AS pathogenesis. Prospective, genotype-stratified studies are needed to confirm these findings and further clarify the contribution of MEFV variants to AS. Muhammed Bahaddin Ates: writing – review and editing, writing – original draft, visualization, methodology, formal analysis, data curation, conceptualization. Bugra Han Egeli: writing – review and editing. Serdal Ugurlu: writing – review and editing, supervision, methodology, conceptualization. The authors have nothing to report. The authors have nothing to report. The study was approved by the Istanbul University–Cerrahpaşa Ethical Committee (reference code: nq09KzAR). Verbal informed consent was obtained from all participants. The authors declare no conflicts of interest. The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.
Ates et al. (Sun,) studied this question.