Ustekinumab for the treatment of psoriasis and psoriatic arthritis: a drug evaluation and literature review

Expert Opin Biol Ther. 2018 Jul;18(7):821-827. doi: 10.1080/14712598.2018.1492545. Epub 2018 Jul 9.

Abstract

Psoriasis (PsO) is an inflammatory disorder characterized by proliferation of keratinocytes, and it may be associated with a systemic inflammatory articular disorder, psoriatic arthritis (PsA). The presentations of PsO and PsA are heterogeneous, and our understanding of pathogenesis has led to a better understanding of the role of the interleukin (IL)-23/T-helper 17 (Th17) axis. Areas covered: Ustekinumab is a monoclonal antibody against IL-12 and IL-23. The pathogenesis of PsO and PsA is a multifactorial process involving genetic, environmental, and lifestyle factors. IL-23 signaling and activation of Th17 cells leads to a self-perpetuating inflammatory loop resulting in continuous keratinocyte proliferation and synovitis. Treatment options are varied, ranging from topical therapy to injection of targeted biologic disease-modifying antirheumatic drugs (bDMARDs). Evidence on the use of ustekinumab in the management of PsO is strong, but it is not as impressive in management of PsA. Expert opinion: IL-12/23 inhibition appears to be a good first-line option for plaque PsO, but efficacy in PsA does not compare favorably to IL-17 inhibition. In general, poorer responses to therapy with any bDMARD in PsA cohorts highlight psoriatic disease heterogeneity. Until new knowledge can remedy the failure of monotherapy, synergistic methods may have to be explored, including combination biologic therapy.

Keywords: Ustekinumab; biologic; interleukin-23; psoriasis; psoriatic arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Psoriatic / drug therapy*
  • Biological Therapy / methods
  • Drug Evaluation
  • Humans
  • Interleukin-12 / immunology
  • Interleukin-17 / immunology
  • Interleukin-23 Subunit p19 / immunology
  • Psoriasis / drug therapy*
  • Th17 Cells / immunology
  • Ustekinumab / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • IL17A protein, human
  • IL23A protein, human
  • Interleukin-17
  • Interleukin-23 Subunit p19
  • Interleukin-12
  • Ustekinumab