What is the first-line treatment for Familial Mediterranean Fever (FMF)?

First-Line Treatment for Familial Mediterranean Fever (FMF)

Colchicine is the first-line treatment for Familial Mediterranean Fever and should be started as soon as a clinical diagnosis is made. 1, 2

Colchicine Dosing and Administration

Initial Dosing

Colchicine should be initiated at age-appropriate doses:

• Children <5 years: 0.5 mg/day (0.6 mg/day if tablets contain 0.6 mg)
• Children 5-10 years: 0.5-1.0 mg/day
• Children >10 years and adults: 1.0-1.5 mg/day 1, 2

Dosing Strategy

• Colchicine can be administered as a single daily dose or divided doses, depending on patient tolerance and adherence 1
• Single doses may be more convenient but can cause more gastrointestinal side effects 1
• Maximum recommended dose: 2 mg/day for children and 3 mg/day for adults 1

Dose Adjustment

• If attacks persist or subclinical inflammation continues (elevated CRP or SAA), increase the colchicine dose gradually within the recommended range 1
• Dose increases should be made no more frequently than weekly 1
• During periods of physical or emotional stress that may trigger FMF attacks, temporary dose increases may be appropriate 1

Monitoring

Regular Assessment

• Monitor patients every 3-6 months 1, 2
• Evaluate:
  • Attack frequency and severity
  • Inflammatory markers (CRP, SAA)
  • Liver enzymes (reduce dose if >2× upper limit of normal)
  • Complete blood count
  • Renal function 1, 2

Special Considerations

• In patients with decreased renal function, monitor closely for signs of colchicine toxicity and adjust dose accordingly 1
• Colchicine should not be discontinued during conception, pregnancy, or lactation 1

Management of Colchicine Resistance

Colchicine resistance is defined as ≥1 attack per month over a 3-month period despite maximum tolerated dose 1, 2

Second-Line Treatment

• For patients not responding to maximum tolerated colchicine doses, add IL-1 inhibitors 1, 2, 3
• Options include:
  • Anakinra: 100 mg/day or 2 mg/kg subcutaneously daily
  • Canakinumab: 150-300 mg or 2-4 mg/kg subcutaneously every 4-8 weeks
  • Rilonacept: 2.2 mg/kg (maximum 160 mg) subcutaneously weekly 1, 3, 4

Management of Specific Symptoms

• During acute attacks: Continue regular colchicine dose and add NSAIDs for symptomatic relief 1, 2
• For protracted febrile myalgia: Glucocorticoids are most effective; NSAIDs and IL-1 blockade are alternatives 2
• For chronic arthritis: Consider additional treatments such as DMARDs, intra-articular steroid injections, or biologics 1, 2

Common Pitfalls and Caveats

• Adherence issues: Poor adherence is a common cause of treatment failure; always assess before labeling a patient as colchicine-resistant 1
• Drug interactions: Colchicine has numerous drug interactions due to metabolism via CYP450 3A4 and P-glycoprotein transport 4
• Gastrointestinal side effects: Common with colchicine; consider lactose-free diet and treatment of intestinal bacterial overgrowth to improve tolerance 5
• Narrow therapeutic window: Colchicine has a narrow therapeutic range; monitor closely for toxicity, especially in patients with renal or hepatic impairment 4
• Incomplete protection: Colchicine may not prevent all manifestations of FMF, such as protracted febrile myalgia or exertional leg pain 4

The primary goal of FMF treatment is to prevent attacks and subclinical inflammation, thereby reducing the risk of amyloidosis and improving quality of life 1. With appropriate colchicine dosing and monitoring, most patients can achieve good disease control.