Colchicine resistance and intolerance in familial mediterranean fever: Definition, causes, and alternative treatments

https://doi.org/10.1016/j.semarthrit.2017.03.006Get rights and content
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Abstract

Background

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory syndrome characterized by recurrent serositis or arthritis attacks and, in some patients, chronic subclinical inflammation that predisposes to secondary amyloidosis. Colchicine is the gold standard of treatment, which reduces attack frequency and amyloidosis risk. However, up to 5% of patients are considered resistant or inadequately respond to colchicine, and some others cannot tolerate the side effects of effective doses of colchicine (colchicine intolerant).

Methods

We examine how the definition of colchicine resistance has evolved along with various characteristics of colchicine that may help explain unresponsiveness to the drug.

Results

Key factors in assessing colchicine resistance include attack frequency and severity, levels of acute phase reactants, colchicine dosage and composition, and treatment compliance. Promising clinical results have been obtained with biologics targeting interleukin-1 in colchicine-resistant or -intolerant patients with FMF.

Conclusions

These results underscore the need to identify patients who are not optimally managed with colchicine and who might therefore benefit from additional biologic therapies.

Abbreviations

ACR
American College of Rheumatology
CRP
C-reactive protein
CYP
cytochrome P450
ER
extended release
ESR
erythrocyte sedimentation rate
EULAR
European League Against Rheumatism
FAVOR
FMF Arthritis Vasculitis and Orphan Disease Research in Pediatric Rheumatology
FDA
Food and Drug Administration
FMF
familial Mediterranean fever
HRQOL
health-related quality of life
IL-1
interleukin-1
NF-κB
nuclear factor-kappa B
P-gp
P-glycoprotein
SAA
serum amyloid A
VAS
visual analog scale

Keywords

Colchicine resistance
Familial Mediterranean fever
Interleukin-1
Second-line therapy

Cited by (0)

The development of this manuscript was sponsored and funded by Novartis Pharma AG.