Reviews
IL-1 inhibition in familial Mediterranean fever: clinical outcomes and expectations
F. Kharouf1, T. Tsemach-Toren2, E. Ben-Chetrit3
- Department of Medicine and Rheumatology Unit, Hadassah Medical Center and the Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
- Department of Medicine and Rheumatology Unit, Hadassah Medical Center and the Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
- Rheumatology Unit, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel. eldad@hadassah.org.il
CER16067
2022 Vol.40, N°8
PI 1567, PF 1574
Reviews
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PMID: 36062765 [PubMed]
Received: 19/07/2022
Accepted : 22/07/2022
In Press: 30/08/2022
Published: 14/09/2022
Abstract
Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease, characterised by recurrent episodes of fever and serositis. Since 1972, colchicine is the drug of choice for FMF. It is effective in preventing the attacks and withholding amyloidosis in most patients with FMF. Colchicine blood and tissue levels are regulated by a glycoprotein pump (GLP) and by Cytochrome P450 3A4 (CYP450 3A4). It is secreted through the bile system and the kidneys. Over the years several problems have been raised following the use of colchicine in FMF. These include potential side effects (particularly gastrointestinal), non-compliance, inefficacy due to drug resistance, many drug-drug interactions and high risk for intoxication due to a narrow therapeutic range. In addition, colchicine does not prevent protracted febrile myalgia or exertional leg pain. Based upon our current understanding of the pathogenesis of FMF, it seems that anti-interleukin-1 (anti-IL-1) agents can solve many of the aforementioned problems related to colchicine therapy. The gastrointestinal side effects of colchicine are extremely uncommon with anti-IL-1 biologics. Drug-drug interactions are also unlikely, and their therapeutic window is not narrow. The once daily injection of anakinra, the once weekly injection of rilonacept, and the once monthly injection of canakinumab result in a better compliance to therapy. Nevertheless, there are no controlled trials showing the efficacy of anti-IL-1 agents in preventing amyloidosis or their safety in pregnancy. Therefore, it is still needed to give IL-1 blockers with concomitant colchicine in its tolerable dose effective in preventing amyloidosis (1.5 mg daily in adult).
