Ustekinumab in treatment of Crohn's disease: design, development, and potential place in therapy

Drug Des Devel Ther. 2016 Nov 11;10:3685-3698. doi: 10.2147/DDDT.S102141. eCollection 2016.

Abstract

Crohn's disease is characterized by a dysregulation of both innate and adaptive immunity responses. Interleukin-12/23 (IL-12/23) pathway has been found to be a major driver of inflammation in adaptive immune responses. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23 and prevents their interaction with their cell surface receptor and further cytokine activation. It is currently approved in the management of plaque psoriasis and psoriatic arthritis. Very promising data have emerged through phase II and phase III trials (UNITI-1, UNITI-2, and IM-UNITI) for both induction and maintenance of clinical response and remission in moderate-to-severe Crohn's disease, resulting in approval by the Food and Drug Administration for this condition. This article reviews the immunology of the IL-12/23 pathway, available data regarding the initial designing of ustekinumab, drug development through clinical trials including pharmacokinetics, efficacy, and safety, and its potential place in the treatment of Crohn's disease.

Keywords: Crohn’s disease; inflammatory bowel disease; interleukin-12; interleukin-12/23 monoclonal antibody; interleukin-23; ustekinumab.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Arthritis, Psoriatic / drug therapy*
  • Crohn Disease / drug therapy*
  • Crohn Disease / physiopathology
  • Humans
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / metabolism
  • Interleukin-23 / antagonists & inhibitors*
  • Interleukin-23 / metabolism
  • Ustekinumab / administration & dosage
  • Ustekinumab / chemistry
  • Ustekinumab / pharmacology*
  • Ustekinumab / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-23
  • Interleukin-12
  • Ustekinumab