IL-1 inhibition in familial Mediterranean fever: clinical outcomes and expectations.

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).

Autoimmune phenomena following SARS-CoV-2 vaccination.

Vaccines represent an attractive possible solution to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Widespread vaccine distribution has yet to occur in most countries, partially due to public concerns regarding possible side effects. While studies indicate the vaccine is exceptionally safe, rare systemic side effects remain possible. In Israel, where a large percentage of the population has been rapidly vaccinated, such adverse events may be more apparent. We report a series of patients presenting with de-novo or flares of existing autoimmune conditions associated with the Pfizer BNT162b2 mRNA SARS-CoV-2 vaccine. All patients were assessed in our tertiary care center in Israel and had no history of previous SARS-COV-2 infection. We observed that while immune phenomena may occur following vaccination, they usually follow a mild course and require modest therapy. We briefly expound on the theoretical background of vaccine related autoimmunity and explore future research prospects.