Unveiling the Efficacy, Safety, and Tolerability of Anti-Interleukin-1 Treatment in Monogenic and Multifactorial Autoinflammatory Diseases

Abstract

Autoinflammatory diseases (AIDs) are heterogeneous disorders characterized by dysregulation in the inflammasome, a large intracellular multiprotein platform, leading to overproduction of interleukin-1(IL-1)β that plays a predominant pathogenic role in such diseases. Appropriate treatment is crucial, also considering that AIDs may persist into adulthood with negative consequences on patients’ quality of life. IL-1β blockade results in a sustained reduction of disease severity in most AIDs. A growing experience with the human IL-1 receptor antagonist, Anakinra (ANA), and the monoclonal anti IL-1β antibody, Canakinumab (CANA), has also been engendered, highlighting their efficacy upon protean clinical manifestations of AIDs. Safety and tolerability have been confirmed by several clinical trials and observational studies on both large and small cohorts of AID patients. The same treatment has been proposed in refractory Kawasaki disease, an acute inflammatory vasculitis occurring in children before 5 years, which has been postulated to be autoinflammatory for its phenotypical and immunological similarity with systemic juvenile idiopathic arthritis. Nevertheless, minor concerns about IL-1 antagonists have been raised regarding their employment in children, and the development of novel pharmacological formulations is aimed at minimizing side effects that may affect adherence to treatment. The present review summarizes current findings on the efficacy, safety, and tolerability of ANA and CANA for treatment of AIDs and Kawasaki vasculitis with a specific focus on the pediatric setting.

Hints for Genetic and Clinical Differentiation of Adult-Onset Monogenic Autoinflammatory Diseases

“…The first step for the diagnosis of mAIDs is to review carefully all details of fever episodes and response to treatment, since examination between attacks may be unrevealing, and tailor the potentially enormous laboratory evaluation to a few tests focusing on the most likely diagnoses. For instance, a favourable response to colchicine prophylaxis is a major diagnostic clue to the diagnosis of FMF [236], whereas constitutive activation of the IL-1 secreting platform is the backstory of CAPS, which dramatically responds to IL-1 antagonists [237]. The discovery of a causative link between autoinflammation and IL-1 release has improved our understanding of the intimate mechanisms of innate immunity, and have likewise led to the identification of extraordinary treatments for many of these disorders [238][239][240].…”

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events*

“…No cases of canakinumab-related anaphylaxis have been reported in the current literature [127]. In addition, patients with anaphylaxis to anakinra have been shown to tolerate canakinumab very well [122].…”

Anakinra for Treatment-Resistant Kawasaki Disease: Evidence from a Literature Review

“…A big advantage of this drug over the other anti-IL-1 agents is the rapid onset of action and the short half-life of 4-6 h; these aspects confer the advantages of being able to quickly test the response and limit the effects in the case of a serious adverse event [7]. This makes the drug an extremely manageable treatment in clinical practice.…”