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

Int J Mol Sci. 2019 Apr 17;20(8):1898. doi: 10.3390/ijms20081898.

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.

Keywords: Interleukin-1; Kawasaki disease; anakinra; autoinflammatory disease; canakinumab; child; innovative biotechnologies; pediatrics; personalized medicine; systemic juvenile idiopathic arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / immunology
  • Cryopyrin-Associated Periodic Syndromes / drug therapy*
  • Cryopyrin-Associated Periodic Syndromes / immunology
  • Familial Mediterranean Fever / drug therapy*
  • Familial Mediterranean Fever / immunology
  • Fever / drug therapy*
  • Fever / immunology
  • Hereditary Autoinflammatory Diseases / drug therapy*
  • Hereditary Autoinflammatory Diseases / immunology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / adverse effects
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Interleukin-1beta / immunology
  • Mevalonate Kinase Deficiency / drug therapy*
  • Mevalonate Kinase Deficiency / immunology
  • Mucocutaneous Lymph Node Syndrome / drug therapy*
  • Mucocutaneous Lymph Node Syndrome / immunology
  • Receptors, Interleukin-1 / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Receptors, Interleukin-1
  • canakinumab

Supplementary concepts

  • Periodic fever, familial, autosomal dominant