Treatment of Familial Mediterranean Fever When Colchicine Fails to Control Attacks
Clinical Scenario
Familial Mediterranean fever (FMF) is initially managed with colchicine to suppress recurrent febrile attacks and subclinical inflammation. When that first-line approach does not achieve its targets, a defined next-line protocol applies.
First-Line Failure Condition
Colchicine (the standard first-line oral therapy) did not achieve complete control of unprovoked attacks and did not minimise subclinical inflammation between attacks — specifically, serum amyloid A protein and C-reactive protein levels remained elevated between episodes.
Next-Line Approach — Partial Overview
This protocol calls for a targeted biological therapy, coadministered alongside continuing colchicine. The specific agent selection, full regimen, and monitoring plan are detailed in the structured protocol.
Treatment Goals
Complete control of FMF attacks and minimised subclinical inflammation between attacks.
References
DOI: 10.1136/annrheumdis-2015-208690
- Evidence for therapeutic options for patients resistant or intolerant to colchicine is limited, but case reports and case series have suggested that IL-1 blockade is a promising second-line therapy.
- A recent small randomised controlled trial (n=14) of the IL-1 blocker rilonacept in colchicine-resistant patients with FMF reported a significant reduction in the number of attacks.
- Phase III trials with canakinumab and anakinra are currently being conducted.
- Tumour necrosis factor (TNF) inhibitors have also been used in colchicine-resistant patients, especially with articular involvement, with good responses reported in observational studies.
- It is recommended that colchicine should be coadministered with alternative biological therapies given that it may reduce the risk of amyloidosis despite persistence of attacks.
- The ultimate goal of treatment in FMF is to obtain complete control of unprovoked attacks and minimise subclinical inflammation in between attacks.
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