Familial mediterranean fever medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]


The mainstay of treatment for familial Mediterranean fever is medical therapy with colchicine. Exertional leg pain may be treated with NSAIDs. Glucocorticoids may be indicated in case of protracted febrile myalgia. Although there is no alternative for colchicine in case of colchicine resistance, IL-1-blockade may be useful.

Medical Therapy



  • 1.2-1.8 mg PO daily (maximum, 3 mg per day)
  • Higher initial doses (up to 2 mg per day) may be indicated in those with:


  • Children younger than 5 years of age, =< 0.5 mg per day (maximum, 0.6 mg per day)
  • Children aged 5 to 10 years of age, 0.5 to 1 mg per day (maximum, 1.2 mg per day)
  • Children older than 10 years of age, 1 to 1.5 mg per day (maximum, 2 mg per day)

Parenteral colchicine

  • Colchicine may be administered intravenously every week in critically ill patients, but this method is associated with increased risk of toxicity.[2][3]

Specific instructions

  • It is generally recommended to give the dose once daily. However, it may be divided in case of side effects.[4]
  • After initiation of therapy, the patient should be evaluated closely for 3 to 6 months to assess its efficacy on attack severity and frequency.
  • Treatment preferably should be initiated with a low dose and then the dose be increased according to the patients' response.
  • The persistence of attacks or sub clinical inflammation is an indication to increase the dose of colchicine.
  • Emotional or physical stress can trigger FMF attacks. Temporary increase in colchicine dose may be considered during stress.
  • During medical therapy with colchicine, liver function test should be monitored regularly; any elevation greater than twofold the upper limit of normal is an indication for dose reduction.
  • CRP, or SAA, or both should be monitored at least every three months during dosage increase to determine the necessary dose.
  • Colchicine may be continued during conception, pregnancy, and lactation. However, dose and frequency of usage may be adjusted according to disease activity.
  • In case of decreased renal function, symptoms and signs of colchicine toxicity as well as CPK level should be monitored regularly to reduce colchicine dose accordingly.
  • In case of preexisting severe renal insufficiency (GFR< 10 ml/min), colchicine dosage should be decreased to 50% due to the potential renal toxicity.
  • Dose reduction may be considered in a patient with no attack for more than 5 years and no elevation in acute phase reactant.

Side effects




  • Theses medications may shorten the duration of attack, but may also increase the frequency of attacks.[9]
  • Indications:

Disease modifying anti rheumatic drugs (DMARDs)


  • Chronic arthritis refractory to treatment with colchicine


  • Indications:[1]
    • Compliant patients who continue to have ≥ 1 attacks each month despite receiving the maximally tolerated dose for at least 6 months are considered to be a non-responder or resistant to colchicine therapy; alternative biological treatments are indicated.
    • According to the recent data, anakinra and canakinumab treatments had a positive effect on both the development and the intensity of FMF episodes.[12][13]


  1. 1.0 1.1 Ozen, Seza; Demirkaya, Erkan; Erer, Burak; Livneh, Avi; Ben-Chetrit, Eldad; Giancane, Gabriella; Ozdogan, Huri; Abu, Illana; Gattorno, Marco; Hawkins, Philip N; Yuce, Sezin; Kallinich, Tilmann; Bilginer, Yelda; Kastner, Daniel; Carmona, Loreto (2016). "EULAR recommendations for the management of familial Mediterranean fever". Annals of the Rheumatic Diseases. 75 (4): 644–651. doi:10.1136/annrheumdis-2015-208690. ISSN 0003-4967.
  2. Rozenbaum M, Boulman N, Feld J, Avshovich N, Petrovich S, Elias M, Slobodin G, Rosner I (2009). "Intravenous colchicine treatment for six months: adjunctive therapy in familial Mediterranean fever (FMF) unresponsive to oral colchicine". Clin. Exp. Rheumatol. 27 (2 Suppl 53): S105. PMID 19796546.
  3. Lidar M, Kedem R, Langevitz P, Pras M, Livneh A (December 2003). "Intravenous colchicine for treatment of patients with familial Mediterranean fever unresponsive to oral colchicine". J. Rheumatol. 30 (12): 2620–3. PMID 14719203.
  4. 4.0 4.1 Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E, Giancane G, Ozdogan H, Abu I, Gattorno M, Hawkins PN, Yuce S, Kallinich T, Bilginer Y, Kastner D, Carmona L (April 2016). "EULAR recommendations for the management of familial Mediterranean fever". Ann. Rheum. Dis. 75 (4): 644–51. doi:10.1136/annrheumdis-2015-208690. PMID 26802180.
  5. Putterman C, Ben-Chetrit E, Caraco Y, Levy M (December 1991). "Colchicine intoxication: clinical pharmacology, risk factors, features, and management". Semin. Arthritis Rheum. 21 (3): 143–55. PMID 1788551.
  6. Ben-Chetrit E, Levy M (August 1998). "Colchicine: 1998 update". Semin. Arthritis Rheum. 28 (1): 48–59. PMID 9726336.
  7. Roldan, Rosa; Ruiz, Adela M.; Miranda, Maria D.; Collantes, Eduardo (2008). "Anakinra: New therapeutic approach in children with Familial Mediterranean Fever resistant to colchicine". Joint Bone Spine. 75 (4): 504–505. doi:10.1016/j.jbspin.2008.04.001. ISSN 1297-319X.
  8. Ben-Zvi I, Livneh A (May 2014). "Colchicine failure in familial Mediterranean fever and potential alternatives: embarking on the anakinra trial". Isr. Med. Assoc. J. 16 (5): 271–3. PMID 24979828.
  9. Amital H, Ben-Chetrit E (2004). "Therapeutic approaches to familial Mediterranean fever. What do we know and where are we going to?". Clin. Exp. Rheumatol. 22 (4 Suppl 34): S4–7. PMID 15515775.
  10. Kaplan E, Mukamel M, Barash J, Brik R, Padeh S, Berkun Y, Uziel Y, Tauber T, Amir J, Harel L (2007). "Protracted febrile myalgia in children and young adults with familial Mediterranean fever: analysis of 15 patients and suggested criteria for working diagnosis". Clin. Exp. Rheumatol. 25 (4 Suppl 45): S114–7. PMID 17949564.
  11. Demirag, Mehmet D.; Ozturk, Mehmet A.; Goker, Berna; Haznedaroglu, Seminur (2008). "Intramuscular gold for the treatment of seronegative spondyloarthropathy associated with familial Mediterranean fever". Rheumatology International. 29 (1): 77–79. doi:10.1007/s00296-008-0631-7. ISSN 0172-8172.
  12. Özen, Seza; Bilginer, Yelda; Aktay Ayaz, Nuray; Calguneri, Meral (2011). "Anti-Interleukin 1 Treatment for Patients with Familial Mediterranean Fever Resistant to Colchicine: Table 1". The Journal of Rheumatology. 38 (3): 516–518. doi:10.3899/jrheum.100718. ISSN 0315-162X.
  13. Meinzer, Ulrich; Quartier, Pierre; Alexandra, Jean-François; Hentgen, Véronique; Retornaz, Frédérique; Koné-Paut, Isabelle (2011). "Interleukin-1 Targeting Drugs in Familial Mediterranean Fever: A Case Series and a Review of the Literature". Seminars in Arthritis and Rheumatism. 41 (2): 265–271. doi:10.1016/j.semarthrit.2010.11.003. ISSN 0049-0172.