Anti-Interleukin-1 Agents in Adult Onset Still's Disease

Abstract

<jats:p>Interleukin 1<jats:italic>β</jats:italic>(IL-1<jats:italic>β</jats:italic>) is emerging as a master mediator of adult onset Still’s disease (AOSD) pathogenesis. This pleiotropic cytokine, whose expression is under the control of the inflammasome pathway, has a wide type of effects. As a key mediator of innate immunity is a potent pyrogen and facilitates neutrophilic proliferation and diapedesis into the inflamed tissues, which are key AOSD manifestations. The study of proinflammatory cytokines profiles in sera and pathological tissues of AOSD patients has shown elevated levels of IL-1<jats:italic>β</jats:italic>, these levels being highly correlated with disease activity and severity. These experimental evidences and the analogy with other autoinflammatory diseases that share with AOSD clinical and biological characteristics have suggested the blockade of IL-1<jats:italic>β</jats:italic>as a possible new therapeutic option for the AOSD, especially in conventional therapy resistant cases. Anakinra, the first anti-IL-1 agent put on the market, has demonstrated capable to induce a rapid response sustained over time, especially in systemic forms, where anti-TNF<jats:italic>α</jats:italic>failed to control symptoms. While a growing number of evidences supports the utilisation of anakinra in AOSD, a new generation of anti-IL1<jats:italic>β</jats:italic>antagonists is developing. Canakinumab and rilonacept, thanks to their higher affinity and longer half-life, could improve the management of this invalidating disease.</jats:p>

Adult-onset Still’s disease: evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers

“…In fact, it is well-known that both steroids and MTX present strong anti-inflammatory and immunosuppressive effects [52–54]. Recently, multiple lines of evidence reported the efficacy of biologic agents in controlling AOSD clinical symptoms in steroids- and sDMARD-refractory AOSD [55–57]. In our cohort, according with the suggestions of Jamilloux et al [58], patients resistant to “traditional” therapies were treated with TNF-inhibitors or with IL-1 or IL-6 antagonists.…”

Interleukin 1 gene polymorphism and susceptibility to disease

“…As in children, IL-1, and specifically, activated IL-1β, plays a crucial role in the pathogenesis of adult onset Still's disease, and the disease activity is correlated with the serum levels of IL-1β. 87,88 Anakinra has been used for the treatment of Still's disease with satisfactory results, based on isolated case reports, and a single prospective randomized open-label clinical trial. 89,90 Canakinumab was successfully used in patients with Still's disease who were refractory to Anakinra.…”

Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart

“…This cytokine is responsible for systemic inflammation and can stimulate the destruction of cartilage and bone. Compelling evidence for IL-1b involvement in AOSD has mostly emerged from the dramatic efficacy of IL-1-inhibiting treatments [54,55]. Concurrent with the clinical response, many disease-associated changes in gene expression in mononuclear cells revert to normal.…”