Novel biologic therapies in development targeting IL-12/IL-23

J Eur Acad Dermatol Venereol. 2010 Oct:24 Suppl 6:5-9. doi: 10.1111/j.1468-3083.2010.03830.x.

Abstract

Recent research has identified the importance of interleukin 12 (IL)-12 and IL-23 in the immunopathogenesis of psoriasis. The p40 subunit common to IL-12 and IL-23 is an attractive target for selective therapy. Clinical study data are available for two anti-IL-12/23 therapies: ustekinumab (CNTO 1275, approved in 2009 for treatment of plaque psoriasis) and ABT-874. The Phase 3 clinical trials PHOENIX 1 and PHOENIX 2 have shown significant benefit for ustekinumab in moderate-to-severe plaque psoriasis, with PASI 75 response rates ranging from 66% at week 12 (after two injections) and rising to 85% at week 24 (after three injections). Withdrawal of treatment led to a gradual return of psoriasis whereas continued therapy every 12 weeks with ustekinumab maintained PASI 75 response. Analysis of safety data demonstrated a safety profile similar to placebo at week 12 and did not reveal any major safety concerns in blocking IL-12 and IL-23 for periods as long as 18 months. Phase 2 data indicate that ABT-874 is also efficacious in the treatment of moderate-to-severe plaque psoriasis across a range of dosing strategies.

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Biological Therapy*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Interleukin-12 / immunology
  • Interleukin-23 / immunology
  • Psoriasis / immunology
  • Psoriasis / therapy*
  • Severity of Illness Index
  • Treatment Outcome
  • Ustekinumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • Interleukin-23
  • Interleukin-12
  • briakinumab
  • Ustekinumab