Approach

Colchicine is the only established treatment for patients diagnosed with FMF (first demonstrated in 1972) and can prevent the potentially fatal complication renal amyloidosis.[68][69] It is almost 95% effective (after excluding those who might be intolerant or non-adherent).[90] Colchicine is used to treat acute attacks, suppress attacks, prevent amyloidosis, and stabilise proteinuria in patients with amyloid nephropathy.[68][91] Some patients also use colchicine to treat acute attacks.

Colchicine is not usually used for asymptomatic patients even if FMF mutations have been identified. Family members of an index case with elevated acute-phase reactants and carrying the same mutation(s) as the symptomatic family member should receive colchicine treatment, as they may develop full FMF symptoms later in life and may be at risk for secondary amyloidosis.

Acute attacks

Acute attacks are treated with analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for symptom relief.

A transient increase in the dose of colchicine should be discouraged due to its inconsistent effectiveness and an increased risk of side effects.[92] When increased doses of colchicine are used to treat an FMF attack, the following considerations are mandatory:

  • Increase the doses only during the prodrome of the attack

  • Never exceed the maximum daily dose

  • Monitor side effects

  • Return to the patient's 'normal' dose immediately after the attack.

Protracted myalgia

Patients with continuing myalgia may require adjunctive therapy with prednisolone and/or an NSAID for as long as 6 weeks, but may also respond to colchicine alone.[53][72][93]

Lifelong prophylaxis

Patients require lifelong treatment with daily colchicine. Initially, adherence might be poor due to adverse effects including diarrhoea, nausea, abdominal cramps, and bloating. However, long-term colchicine therapy is highly effective and safe with mild and infrequent adverse effects. Intravenous colchicine use is discouraged due to the potential to cause severe bone marrow suppression and death. Adjunctive biological agents have been used and found effective for patients who respond poorly or have poor tolerance to colchicine.[94][95][96]

Currently, evidence supporting the use of biological agents is limited. Functional studies suggest that interleukin (IL)-1 is implicated in the inflammatory reaction in FMF; therefore, IL-1 inhibitors are thought to be a good approach in resistant FMF. Studies have confirmed the good response of colchicine-resistant FMF patients to IL-1 inhibitors.[97][98][99] One Cochrane review concluded that anakinra and canakinumab are probably effective, but more research is needed for rilonacept.[100] IL-1 inhibitors are now tried first for colchicine-resistant and/or intolerant patients.[101] Even if an increasing number of IL-1 targeting drugs are currently available, treatment should start with a short half-life drug (i.e., anakinra) in order to test effectiveness. Medium or long half-life drugs (i.e., rilonacept, canakinumab) should be considered only if the short half-life drug is effective.[99][102] Canakinumab and anakinra are approved for FMF in some countries.

Tumour necrosis factor (TNF)-alpha antagonists have also been tested in colchicine-intolerant patients with articular involvement, and they have been shown to be a good therapeutic option for most of them. TNF antagonists could be considered in resistant FMF patients with important articular involvement.[102][103]

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