colchicineresistance

Colchicine resistance refers to the lack of adequate clinical response to colchicine therapy at doses that are otherwise tolerated. It is discussed most often in familial Mediterranean fever (FMF) but can also be described in gout and recurrent pericarditis. It is important to distinguish resistance from intolerance (where adverse effects limit dose) and from nonadherence or misdiagnosis of disease activity.

Causes and potential mechanisms include nonadherence, underdosing, or drug interactions that reduce colchicine exposure (for example, inhibitors of CYP3A4 or P-glycoprotein). True pharmacodynamic resistance is not well understood; genetic and inflammatory pathway variation, especially in FMF with MEFV mutations and dysregulated IL-1 signaling, may influence response. Other comorbidities or concurrent infections can mimic or mask disease activity, complicating assessment.

Diagnosis and evaluation involve confirming adherence, reviewing dosing, and examining drug interactions and absorption. Exclude intolerance as a limiting factor. If appropriate, optimize the colchicine dose to the maximum tolerated level according to clinical guidelines, with careful monitoring for toxicity such as neutropenia, myopathy, or gastrointestinal adverse effects.

Management strategies depend on the underlying condition. In FMF with colchicine resistance, escalation to higher doses is often considered, and IL-1–targeted therapy (such as canakinumab or anakinra) may be recommended for patients with continued attacks or inflammation. In gout or recurrent pericarditis, similar use of IL-1 blockade or other targeted anti-inflammatory approaches can be used on a case-by-case basis, alongside efforts to improve adherence and manage comorbidities.