From the Guidelines
Familial Mediterranean Fever (FMF) should be treated with colchicine as soon as a clinical diagnosis is made, with the dose adjusted based on age, response, and tolerance, as it is the most effective way to prevent inflammatory attacks and reduce the risk of amyloidosis 1.
Key Considerations for Treatment
- The starting dose of colchicine varies by age: 0.5 mg/day for children under 5 years, 0.5-1.0 mg/day for children between 5-10 years, and 1.0-1.5 mg/day for individuals over 10 years and adults 1.
- The dose can be increased up to 2 mg in children and 3 mg in adults, or the maximum tolerated dose, with monitoring of CRP, SAA protein, or both every 3 months to determine the necessary dose 1.
- Patients who do not respond to the maximum tolerated dose of colchicine or have significant side effects may be considered for alternative treatments, such as IL-1 blockade, which has shown promise in reducing the number of attacks in colchicine-resistant patients 1.
Monitoring and Adjustments
- Regular monitoring of kidney function is crucial, as FMF patients are at risk of developing amyloidosis, which can lead to renal dysfunction 1.
- The development of amyloidosis can often be prevented by suppressing chronic inflammatory activity with colchicine, and complete suppression of inflammatory activity may prevent progression or reverse established amyloidosis 1.
- Dose adjustments should be made based on the patient's response and tolerance, with the option to divide the dose to minimize gastrointestinal side effects, which are common with colchicine therapy 1.
From the Research
Definition and Characteristics of FMF
- Familial Mediterranean Fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and serositis, lasting 12-72 hours 2, 3.
- FMF is associated with mutations in the MEFV gene, which encodes the abnormal pyrin protein, involved in the activation of caspase-1 and the processing and release of active pro-inflammatory IL-1β 3, 4.
- Clinical features of FMF include recurrent episodes of fever, leukocytosis, serositis, arthritis, myalgia, or erysipelas-like skin lesions 3.
Treatment of FMF
- Colchicine is the mainstay of treatment in symptomatic FMF patients, reducing disease activity and preventing secondary amyloidosis and renal damage 2, 3, 5.
- The minimal daily dose of colchicine in adults is 1.0 mg/day, but the dose in children is not well established 2.
- Alternative treatments, such as IL-1 inhibitors (e.g., anakinra, canakinumab), may be considered in colchicine-intolerant or colchicine-resistant patients 3, 5, 4, 6.
- IL-1 inhibitors have shown efficacy in controlling and preventing flares in FMF patients who are insufficiently controlled with colchicine alone 4, 6.
Management of FMF
- Patients experiencing more than four FMF attacks per year may require colchicine dose adjustment 5.
- In cases of persistent attacks despite maximum doses of colchicine, alternative treatment with IL-1 inhibitors should be considered 5.
- Routine genetic testing for MEFV mutations in asymptomatic siblings of an index case is not recommended 5.