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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.
For research purposes, samples of:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Colchicine-resistant Familial Mediterranean Fever patients | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients. | Biological |
For research purposes, samples of:
|
| Measure | Description | Time Frame |
|---|---|---|
| Amount of colchicine measured in the first 2 cm of hair from the scalp of an FMF patient considered colchicine resistant or from pubic hair in patients with bald or colored hair, which corresponds to the average compliance of the last 2 months of intake | To assess 2-month compliance with colchicine in patients with FMF considered resistant via capillary drug dosage | Through study completion, an average of 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation between the amount of colchicine measured in the hair and the blood and urine levels of colchicine attesting to the last days' intake. | To study blood and urine colchicine dosage in FMF patients considered resistant to colchicine | Through study completion, an average of 18 months |
| Correlation between capillary colchicine dosage and colchicine compliance assessed with the 6-item GIRERD |
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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:
Exclusion Criteria:
- Patients participating in another interventional trial
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| Name | Affiliation | Role |
|---|---|---|
| Léa SAVEY, MD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Service de Médecine Interne. Hôpital Tenon, 4 Rue de la Chine | Paris | 75020 | France |
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| ID | Term |
|---|---|
| D002006 | Brucellosis |
| D010505 | Familial Mediterranean Fever |
| D055118 | Medication Adherence |
| ID | Term |
|---|---|
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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|
Compare hair dosing to self-reported compliance |
| Through study completion, an average of 18 months |
| Composition of the fecal microbiota (search for an overrepresentation of clostridiae) in colchicine-resistant patients patients with colchicine resistance | Studying the composition of the fecal microbiota in colchicine-resistant FMF patients | Through study completion, an average of 18 months |
| Testing for clostridioides difficile toxin B in colchicin-resistant patients | Testing colchicine-resistant FMF patients for clostridioides difficile toxin to rule out chronic asymptomatic carriage | Through study completion, an average of 18 months |
| Dosage of proinflammatory cytokines IL1, IL6, IL18, TNFa and il1Ra. | Study blood levels of proinflammatory cytokines in colchicine-resistant patients, in particular IL1 and il1RA | Through study completion, an average of 18 months |
| Percentage of patients for whom a prescription of anti-IL-1 biotherapy could have been avoided (i.e. poor compliance with Colchicine and/or Clostrioides Difficile infection) | Determine the percentage of patients labeled colchicine resistant who were actually noncompliant or chronically infected with pyrin-activating bacteria like clostridioides difficile | Through study completion, an average of 18 months |
| D056660 | Hereditary Autoinflammatory Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010349 | Patient Compliance |
| D010342 | Patient Acceptance of Health Care |
| D000074822 | Treatment Adherence and Compliance |
| D015438 | Health Behavior |
| D001519 | Behavior |