What is the role of colchicine in the treatment of familial Mediterranean fever (FMF)?

Updated: Apr 07, 2020
  • Author: John O Meyerhoff, MD; Chief Editor: Herbert S Diamond, MD  more...
  • Print

Colchicine is so effective in preventing attacks of familial Mediterranean fever (FMF) and preventing the development of amyloidosis that the most important aspects of medical care are to make the correct diagnosis and to institute therapy.

Administer colchicine therapy daily in patients at risk of developing amyloidosis (eg, North African Jewish people, Turkish people, Armenian people living in Armenia). Other Sephardic Jewish people and Arabic people are at lower risk but also probably require daily colchicine therapy.

Daily colchicine is customarily given in a dosage of 0.6 or 0.5 mg twice daily, depending on the dosage form available. However, a study in treatment-naive pediatric patients newly diagnosed with FMF found that a single 1-g daily dose was noninferior to 0.5 mg given twice daily. [19] Guidelines from the European League Against Rheumatism (EULAR) recommend the following starting dosages of colchicine [20] :

  • Children < 5 years of age: ≤0.5 mg/day (≤0.6 mg/day if tablets contain 0.6 mg)
  • Children 5–10 years: 0.5–1.0 mg/day (1.2 mg/day if tablets contain 0.6 mg)
  • Children >10 years and adults:1.0–1.5 mg/day (1.8 mg/day if tablets contain 0.6 mg)

After colchicine has been started, EULAR recommends following patients closely for 3–6 months to observe the therapeutic effect.

In patients who do not respond to twice-a-day dosing, administer colchicine three, or even four, times a day. In patients who have difficulty tolerating colchicine, start therapy at once-a-day dosing and gradually increase the dose. In patients whose conditions were not responsive to oral colchicine, the addition of 1 mg IV once a week reduced the number of attacks in 10 of 13 patients and the severity of attacks in 6 of 13 patients. [21]

Colchicine also stabilizes the amount of proteinuria in patients with amyloid nephropathy. Renal disease may resolve in patients with a creatinine level of less than 1.5 mg/dL who are treated with 1.5 mg/d of colchicine.

Ashkenazi Jewish people and Armenian people living in the United States seem to be at extremely low risk of amyloidosis and may need treatment only to prevent attacks. If attacks are rare and patients can determine when they are beginning, treatment with intermittent colchicine therapy at the onset of attacks may be sufficient.

The regimen for acute attacks in patients not taking daily colchicine is 0.6 mg every hour for 4 doses, then 0.6 mg every 2 hours for 2 doses and then 0.6 mg every 12 hours for 4 doses. Colchicine should be started as soon as the patient recognizes that an attack is occurring. If the initial doses are effective, patients may be able to do without the later doses, but this varies from patient to patient.

A Turkish study found that in children who were heterozygous for MEFV variants and required initiation of colchicine treatment after experiencing symptoms of FMF, colchicine may be successfully discontinued in some cases, if very careful follow-up is provided. In this study, the median duration of colchicine treatment was 36 (range, 24-110) months, and colchicine was discontinued after a median attack- and inflammation-free period of 27 (range, 24-84) months. Colchicine was restarted in 2 of the 22 patients because of symptom recurrence. [22]

A group from another Turkish hospital followed 69 children who were heterozygous for MEFV mutations and did not meet criteria for pediatric FMF. Of these, 39 had known pathogenic mutations and 30 had mutations of unknown significance (E148Q or P369S in 26 cases). None of these children developed persistent proteinuria and only 2 patients who were M694V heterozygous experienced febrile episodes often enough to be started on colchicine. [23]

Some patients treated with colchicine develop lactose intolerance and may respond to a lactose-free diet.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!