Study of Colchicine Resistance in Familial Mediterranean Fever

Study Of Colchicine Resistance In Familial Mediterranean Fever

Five to 10% of familial mediterranean patients are considered colchicine-resistant (i.e. patients with a persistent inflammatory syndrome, despite taking the maximum tolerated dose of colchicine daily). The recommended treatment in this case is a subcutaneous anti-interleukin 1 biotherapy (anakinra or canakinumab). These treatments are expensive (1,000 to 12,000 euros/month).

However, for a patient to be considered colchicine-resistant, compliance with the treatment must be verified. Furthermore specific activation of the pyrin inflammasome by Clostrioides difficile toxin and the overrepresentation of these bacteria in the stools of our patients led us to systematically search for them in our resistant patients. The demonstration of the involvement of C. difficile in the imbalance of the disease has not yet been published.

The colchiresist study aim to better characterize colchicine-resistance by confirming good compliance to treatment with colchicine hair measurement and by looking for clostrioides infection or intestinal dysbiosis.

Patients meeting the criteria for colchicine resistance will be included in a follow-up visit.

• Adherence to colchicine therapy will be assessed by the Girerd questionnaire completed by the patient at the inclusion visit.
• A blood test is performed including a haemogram, CRP and SAA, creatinine and proteinuria.
• a standard stool analysis on site to look for C. difficile toxin.

For research purposes, samples of:

• Stool.
• A strand of hair with the diameter of a pencil and a minimum length of 2 cm, in the region of the posterior vertex, where the growth and integration are relatively constant to avoid variability.
• In patients with baldness or bleached hair only: pubic and/or axillary hair will be taken, The samples will then be processed without segmentation.
• Additional blood (5ml) and urine (2ml) samples for colchicine dosage. The patient's participation ends after this visit

Inclusion Criteria:

Inclusion Criteria Age ≥ 12 years with no upper age limit -Patients with familial Mediterranean fever (FMF) meeting international criteria for the disease (Livneh criteria) and carrying 2 pathogenic mutations in the MEFV gene.

Patients considered colchicine-resistant according to EULAR criteria reviewed by an expert consensus:

• Persistence of signs of activity (at least one attack per month for at least 3 months) despite taking the maximum tolerated dosage of colchicine.
• Persistence of a biological inflammatory syndrome after exclusion of other causes and despite taking a maximum tolerated dosage of colchicine.
• Signature of an informed consent by the patient (or his parents if under 18 years of age)
• Patients affiliated to a social security system

Exclusion Criteria:

- Patients participating in another interventional trial