Comparative analysis of global practices in the management of colchicine-resistant familial Mediterranean fever: a CliPS network analysis

Abstract

Background: Although colchicine is the mainstay of familial Mediterranean fever (FMF) treatment, 5-10% of patients are considered to have colchicine resistance (CR). However, there is no globally agreed CR definition or indications for biological disease-modifying anti-rheumatic drugs (bDMARDs).

Methods: A survey on 'Biologics in Monogenic Autoinflammatory Diseases', part of the 'Clinical Practice Strategies' (CLiPS) initiative, was conducted by a JIR cohort-initiated eCOST network among expert participants worldwide. Our primary aim was to provide a flowchart reflecting the different CR definitions and present data regarding bDMARD indications. The secondary aim was to determine how specific biases influence clinical approaches. We analysed the CliPS according to the experience levels of physicians, country-specific FMF prevalence, countries' gross domestic product, bDMARD availability and reimbursement policies of the countries.

Results: A total of 223 responses from 46 countries were included in the study. Almost half of the respondents (73/160, 45.6%) indicated that three to four attacks within the preceding 6 months were necessary for their CR definition. The most frequently used acute-phase reactant was C-reactive protein (157/164, 95.7%). Almost three-fourths of the respondents (74%, n=165) considered that supplementary factors, including complications of FMF, attack severity, elevated activity scores, patient-reported outcome and quality of life scales, influenced their CR definition.

Conclusion: We present a novel flowchart describing physicians' general attitudes and unique findings regarding management strategies for colchicine-resistant FMF and shifting trends influenced by epidemiological and socioeconomic factors.

Keywords: Amyloidosis; Biological Therapy; Economics; Familial Mediterranean Fever; Interleukin 1 Receptor Antagonist Protein.

Figure 1. A simplified flowchart developed from real-world survey responses, depicting the approaches of clinicians for defining and managing CR in familial Mediterranean fever. The left panel outlines the suspicion phase, highlighting core and optional clinical parameters. The right panel addresses the decision phase, including follow-up duration, dose escalation strategies, and criteria for final CR definition. This figure reflects cumulative clinical reasoning processes used by physicians from diverse healthcare settings. CR, colchicine resistance; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; QOL, quality of life; SAA, serum amyloid A; WBC, white blood cell.