Efficacy and safety of anti-interleukin-6 treatment in familial Mediterranean fever: a systematic literature review

Abstract

Introduction: Biological treatments are indicated in familial Mediterranean fever (FMF) patients with colchicine resistance or intolerance. Interleukin-1 (IL-1) inhibitors may not yield sufficient efficacy and safety. Interleukin-6 inhibitors (tocilizumab - TCZ) have been suggested to be potentially beneficial. This systematic literature review aimed to evaluate the existing data on the efficacy and safety of IL-6 inhibitors in the treatment of FMF. Material and methods: A systematic literature review was conducted using PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify literature published until February 2024 on "Tocilizumab" OR "Interleukin-6 inhibitor" AND "Familial Mediterranean Fever". This study was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: A total of 11 studies were included, corresponding to 68 patients: 6 studies were case reports, 3 were case series, and 2 were randomized control trials. Tocilizumab was indicated mainly for amyloid A (AA) amyloidosis and resistance/intolerance to other drugs. Tocilizumab showed efficacy in controlling FMF attacks and disease symptoms including fever, abdominal pain, arthritis and arthralgia. Inflammatory markers including C-reactive protein and serum amyloid A protein decreased. A decrease in proteinuria levels was reported in 20 patients. Adverse events were recorded in one-third of patients and led to TCZ discontinuation in 5 patients. No deaths associated with anti-IL-6 treatment were documented within a median follow-up period of 13 months. Conclusions: Although the duration of follow-up of TCZ was short, we concluded that TCZ might present an acceptable profile regarding efficacy and safety in adult FMF patients. Our data suggest that TCZ could be a good treatment option after IL-1 inhibitors and warrants further investigation.