Background/Purpose: Familial Mediterranean fever (FMF) is considered the prototype of autoinflammatory diseases, typically regarded as recessively inherited and caused by mutations in the pyrin protein leading to increased activation of IL-1β. Both IL-1β, and IL-17A are found in the joint of psoriatic arthritis (PsA) patients, and IL-23/17 pathway cytokines and TH17 cells are known critical drivers of PsA pathogenesis. Thus, one may speculate that high levels of IL-1 in FMF patients might cause TH17 activation, and increase the risk of PsA.  

 We aimed to assess the association between FMF and PsA using data from a large population database.

Methods: This retrospective cohort study is based on data from a large healthcare provider in the Mediterranean which includes ~4.9 million members. First, we identified all adults aged 18 years or older by January 1^st, 2010 ever diagnosed with FMF and treated with colchicine. Identified patients were frequency matched by sex and age to subjects without FMF using a 1:10 ratio. The group of patients with FMF and the matched group without FMF were followed until the occurrence of PsA, death or end of follow-up, December 31^st 2023, whichever came first. Cox proportional hazard regression analysis was used to assess the association between FMF and PsA adjusting for demographic factors and comorbidities.  

Results: The FMF study group consisted of 6855 subjects, 48.4% males, with a mean age of 41.4 ±15.6 years, matched by age and sex to 68550 controls.  During the follow-up 40 patients in the FMF group developed PsA compared to 115 in the control group, resulting in a crude HR of 3.52 (95%CI 2.45-5.04). The results remained statistically significant in the multivariable model following  adjustment for demographics and comorbidities, HR 3.48 (95% CI 2.42-4.99), and after further adjustment for psoriasis, HR 3.32 (95% CI 2.31-4.78). Patients with PsA and FMF compared to patients with PsA without FMF had a lower socioeconomic status (p=0.02) and lower prevalence of diabetes mellitus (p=0.015). No other significant differences were observed between the two groups in terms of demographics, comorbidities and treatment with conventional, biologic or targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) for PsA during the follow up period.  None of the FMF and PsA patients were treated with IL-1 inhibitors compared to 279 (4.1%) of the FMF patients who did not  develop PsA.

Conclusion: FMF is associated with increased risk of PsA. The positive association between FMF and PsA may point to common pathogenetic pathways and could influence treatment choices.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-risk-of-psoriatic-arthritis-in-patients-with-familial-mediterranean-fever-a-population-based-cohort-study/