IL-6: A new target in crystal-induced arthritides – A narrative review

Abstract

Gout and calcium pyrophosphate deposition disease (CPPD) are two highly prevalent causes of inflammatory arthritis, characterized by the pathological deposition of monosodium urate (MSU) and CPP crystals, respectively, in joint tissues. These crystals can induce an intense inflammatory response, known as crystal-induced inflammation, which involves innate immunity and is highly dependent of the activation of interleukin 1β (IL-1β) following the recruitment of the NLRP3 inflammasome. In patients in whom first-line treatments (colchicine, prednisone, NSAIDs) are either ineffective or inappropriate, IL-1 inhibitors can be used to treat acute crystal-induced arthritis. However, some patients do not respond to these therapies, or experience adverse events. There is therefore a need for other treatments, particularly in CPPD, where the inflammation induced by CPP crystals can be chronic and affect elderly patients, making IL-1 inhibitors a less suitable option. IL-6, which is highly expressed during crystal-induced inflammation, is emerging as a promising therapeutic target in chronic CPP arthritis, with publications reporting the efficacy of tocilizumab in patients with inadequate response to other treatments, including anakinra, the most commonly used IL-1 inhibitor in this indication (off-label). These data require confirmation in randomized controlled trials. Other therapies, such as JAK inhibitors or NLRP3 inhibitors, may also be of interest in crystal-induced arthritis.