What is the best treatment for an acute flare in Familial Mediterranean Fever (FMF)?

Treatment for Acute Flares in Familial Mediterranean Fever

For acute flares of Familial Mediterranean Fever (FMF), continue the usual dose of colchicine and add NSAIDs for symptomatic relief. 1

First-Line Management of Acute Flares

• Continue regular colchicine: Do not discontinue or change the maintenance colchicine dose during an acute flare 1
• Add NSAIDs: Use non-steroidal anti-inflammatory drugs for symptomatic relief during the acute attack 1
• Rule out other causes: Always consider alternative diagnoses when evaluating a suspected FMF attack 1

Colchicine as Cornerstone Therapy

Colchicine is FDA-approved for both prophylaxis and treatment of FMF 2. The appropriate dosing strategy includes:

Age Group	Maintenance 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

Dose Adjustments for Persistent Attacks

If a patient continues to experience frequent attacks despite adherence to the initial colchicine dose:

1. Increase colchicine dose by 0.5 mg/day (or 0.6 mg/day depending on available formulation) 1
2. Do not exceed 2 mg/day in children or 3 mg/day in adults 1
3. Monitor for side effects, particularly gastrointestinal symptoms 1

Management of Special FMF Manifestations

• Protracted febrile myalgia: Glucocorticoids are most effective for symptom resolution; NSAIDs and IL-1 blockade are alternative options 1
• Exertional leg pain: NSAIDs are the suggested treatment 1
• Chronic arthritis: May require additional medications such as DMARDs, intra-articular steroid injections, or biologics 1

For Colchicine-Resistant or Intolerant Patients

Colchicine resistance is defined as ≥1 attack per month over a 3-month period despite maximum tolerated dose 1. For these patients:

1. IL-1 inhibitors are the preferred biological agents with the strongest evidence 1, 3:

   • 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) weekly subcutaneously

2. Other biologics with less evidence include:

   • Anti-TNF agents 4
   • IL-6 inhibitors (tocilizumab) 4, 5

Monitoring and Follow-up

• Assess response to treatment every 3-6 months 1
• Monitor inflammatory markers (CRP, SAA) to evaluate subclinical inflammation 1
• Check liver enzymes regularly; reduce colchicine if >2x upper limit of normal 1
• In patients with decreased renal function, monitor for signs of colchicine toxicity and adjust dose accordingly 1

Common Pitfalls to Avoid

1. Poor adherence: Low adherence to colchicine is a key component of apparent resistance 6
2. Inadequate dosing: Failure to increase colchicine to maximum tolerated dose before declaring resistance 1
3. Drug interactions: Colchicine has numerous drug interactions that can affect efficacy and toxicity 1
4. Discontinuing colchicine when adding biologics: Even when starting IL-1 inhibitors, continue colchicine at the maximum tolerated dose to prevent amyloidosis 3 (though recent evidence suggests IL-1 inhibitor monotherapy may be effective in truly colchicine-intolerant patients 7)

By following this approach, most FMF patients can achieve adequate control of acute flares and prevention of long-term complications such as amyloidosis.