Background/Purpose: Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease and colchicine is the drug of choice for its treatment. However, about 5-10% of FMF patients do not respond to colchicine, even when they are fully compliant. Anti-interleukin(IL)-1 treatments are used for the patients who are resistant to colchicine. Treatment with IL-1 inhibitors have been shown to be effective in clinical trials and in several case series. The objective of this report is to produce evidence-based recommendations to define “colchicine resistance“, as well as compliance and intolerance, to guide rheumatologists and other health professionals in the treatment and follow-up of patients with colchicine-resistant FMF.

Methods: A consensus meeting with 12 experts followed a systemic literature review and Delphi questionnaire. The expert committee consisted of pediatric rheumatologists with expertise in FMF. Parameters for colchicine resistance/intolerance/compliance derived from the literature were evaluated by a pre-meeting online questionnaire. All parameters were discussed with a nominal group technique during the meeting. Recommendations were accepted if more than 80% agreement was reached. If agreement was below 80% a second round of discussion was held.

Results: The systematic literature review yielded 264 articles. Of these, 38 were selected for expert review. After the literature review, Delphi survey, and round table discussion, recommendations that reached consensus levels were:

1. Colchicine is the drug of choice for the treatment of FMF and compliance is a critical issue. For the following statements, it is assumed that the patient is compliant with colchicine.
2. When utilizing colchicine to treat FMF, it is recommended to adjust the dose based on disease activity, with the maximal dose in children depending on age (and weight).
3. The maximum recommended colchicine dose for the treatment of FMF is between 1-3 mg per day, depending on age, limited by signs of toxicity and tolerability.
4. For a patient receiving the maximum tolerated dose of colchicine, resistance to colchicine is defined as ongoing disease activity (as reflected by either recurrent clinical attacks [average one or more attacks per month over a three-month period], or persistently elevated C-reactive protein or serum amyloid A in between attacks [depending on which is available locally)), in the absence of any other plausible explanation.
5. Amyloid A amyloidosis develops as a consequence of persistent inflammation, which may be a manifestation of colchicine resistance.
6. Colchicine intolerance, which generally manifests as gastrointestinal symptoms (such as diarrhea and nausea), is common and can limit the ability to achieve or maintain the effective dose. Dose-limiting toxicity is rare and may include elevated liver function tests, leukopenia, azoospermia etc.
7. Active disease and intolerance to colchicine affect quality of life.
8. Various patient reported outcomes to be used to guide FMF disease management were outlined.

Conclusion: The suggested recommendations are intended to improve patient care in FMF, to make a personalized treatment plan.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/recommendation-on-colchicine-dosing-and-definition-of-colchicine-resistance-intolerance-in-the-management-of-familial-mediterranean-fever/