Medical 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, with a maximum recommended dose of 2 mg/day for children and 3 mg/day for adults. 1
Colchicine Dosing Protocol
The recommended maintenance dose of colchicine varies by age group:
| Age Group | Starting Dose | Maximum Dose |
|---|---|---|
| <5 years | 0.5-0.6 mg/day | 1.2 mg/day |
| 5-10 years | 0.5-1.0 mg/day | 1.8 mg/day |
| >10 years and adults | 1.0-1.5 mg/day | 3.0 mg/day |
- Colchicine can be administered as a single daily dose or divided doses, depending on patient tolerance and adherence 2
- Dose escalation should be done gradually, with increases of 0.5 mg/day (or 0.6 mg/day depending on available formulation) 1
- Wait at least one week between dose increases to monitor for side effects 1
- For patients with pre-existing complications (e.g., amyloidosis) or greater disease activity, higher initial doses may be appropriate 2
Monitoring Protocol
Evaluate:
- Attack frequency and severity
- Inflammatory markers (CRP, SAA)
- Liver enzymes (reduce dose if >2x upper limit of normal)
- Complete blood count
- Renal function
In patients with decreased renal function, the risk of colchicine toxicity is very high; monitor carefully and reduce dose accordingly 2
Management of Colchicine Resistance
Colchicine resistance is defined as ≥1 attack per month over a 3-month period despite maximum tolerated dose and confirmed compliance 1.
For colchicine-resistant patients:
- Verify compliance and proper dosing
- Add IL-1 inhibitors while maintaining colchicine at the maximum tolerated dose 2, 1
IL-1 inhibitor options:
- Canakinumab: FDA-approved for FMF 3
- For patients >40 kg: 150 mg subcutaneously every 4 weeks (can increase to 300 mg if inadequate response)
- For patients ≤40 kg: 2 mg/kg subcutaneously every 4 weeks (can increase to 4 mg/kg if inadequate response)
- Anakinra: Used off-label but with substantial clinical evidence 4, 5
Acute Attack Management
During acute attacks:
- Continue regular colchicine dose
- Add NSAIDs for symptomatic relief 2, 1
- For protracted febrile myalgia, glucocorticoids are most effective; NSAIDs and IL-1 blockade are alternative options 2
- For exertional leg pain, NSAIDs are the suggested treatment 1
Special Considerations
- Colchicine should not be discontinued during conception, pregnancy, or lactation 2
- For chronic arthritis, consider additional treatments such as DMARDs, intra-articular steroid injections, or biologics 2
- During periods of physical or emotional stress that may trigger FMF attacks, temporary dose increases may be appropriate 2
- If a patient is stable with no attacks for more than 5 years and no elevated acute phase reactants, dose reduction could be considered after expert consultation and with continued monitoring 2
Common Pitfalls and Caveats
- Gastrointestinal side effects are common with colchicine. Consider lactose-free diet and treatment of intestinal bacterial overgrowth to improve tolerance 6
- Drug-drug interactions with colchicine can be dangerous due to its narrow therapeutic window. Monitor closely when adding medications metabolized by CYP450 3A4 or affecting P-glycoprotein 4
- Never abruptly discontinue colchicine, even during acute attacks, as this can worsen symptoms 2
- Approximately 10-15% of patients are non-responders or intolerant to colchicine, requiring alternative or additional treatments 6, 4
- When using IL-1 inhibitors, continue colchicine at tolerable doses to help prevent amyloidosis 4