Treatment of Familial Mediterranean Fever (FMF)
Colchicine is the cornerstone of FMF treatment and should be started as soon as a clinical diagnosis is made, with lifelong administration required to prevent attacks and complications. 1
First-Line Treatment: Colchicine
Treatment with colchicine should begin immediately upon clinical diagnosis, even before genetic confirmation, to prevent inflammatory attacks and complications 1
Colchicine dosing is weight-based and age-dependent:
- Children <5 years: ≤0.5 mg/day (≤0.6 mg/day when tablets contain 0.6 mg)
- Children 5-10 years: 0.5-1.0 mg/day (1.2 mg/day for 0.6 mg tablets)
- Children >10 years and adults: 1.0-1.5 mg/day (1.8 mg/day for 0.6 mg tablets) 1
Colchicine can be administered as a single daily dose or divided doses, depending on patient tolerance and adherence 1
Long-term colchicine prophylaxis is essential to control inflammation, prevent clinical attacks, and most importantly, prevent the development of AA amyloidosis 1
Treatment Goals and Monitoring
The primary treatment goal is to achieve minimal or no clinical activity and complete control of subclinical inflammation to prevent associated damage 1
Regular monitoring of acute phase reactants (CRP, SAA) is necessary even in asymptomatic periods to detect subclinical inflammation 1
Adherence to treatment is crucial and should be regularly assessed, especially in adolescents and adults 1
Genetic testing is advised for every patient with suspected FMF, particularly to guide treatment decisions for colchicine-resistant patients 1
Management of Colchicine Resistance or Intolerance
In adherent patients with persistent attacks or subclinical inflammation, colchicine dose should be increased within the recommended range 1
For patients who are truly colchicine-resistant or intolerant, IL-1 inhibitors are the next treatment option 2
Canakinumab (ILARIS) is FDA-approved for FMF treatment at the following doses:
- Patients >40 kg: 150 mg subcutaneously every 4 weeks (can increase to 300 mg if inadequate response)
- Patients ≤40 kg: 2 mg/kg subcutaneously every 4 weeks (can increase to 4 mg/kg if inadequate response) 2
Special Considerations
FMF requires lifelong management with regular follow-up visits and patient education 1
Patient-centered management is essential to promote quality of life and support overall health and well-being 1
Patients with the M694V mutation, especially homozygotes, are at higher risk for amyloidosis and should be monitored more closely 3, 4
Verify medication adherence before diagnosing colchicine resistance, as non-adherence is a common cause of treatment failure 1, 5
Complications and Prevention
AA amyloidosis is the most serious complication of untreated or undertreated FMF, primarily affecting the kidneys and potentially leading to renal failure 3, 6
Regular colchicine treatment significantly reduces the risk of amyloidosis from 60% to less than 13% 1
Other potential complications include infertility, growth retardation in children, and chronic arthritis 7, 5
Genetic counseling should be offered to affected families, especially when the p.Met694Val allele is present, as renal amyloidosis can be prevented by colchicine 4