A short history of biological therapy for psoriatic arthritis

Clin Exp Rheumatol. Sep-Oct 2015;33(5 Suppl 93):S104-8. Epub 2015 Oct 15.

Abstract

Psoriatic arthritis (PsA) is an inflammatory disease characterised by the clinical domains of arthritis, enthesitis, dactylitis, spondylitis, and psoriasis, often causing significant functional disability, loss of quality of life, and premature mortality. Prior to the introduction of targeted biologic medications, such as TNF inhibitors, the capacity to control disease activity was limited, with only modest effects noted in most patients with traditional oral medications such as methotrexate and sulfasalazine. The introduction of TNF inhibitors substantially changed the outlook of PsA patients, yielding significant response in all relevant clinical domains and demonstrating the capacity to inhibit progressive structural damage of joints. However, not all patients responded to these agents and many patients displayed initial response which waned over time, partly due to immunogenicity (development of antibodies which blocked full therapeutic effect of the biologic protein), or because of poor tolerability and/or adverse events. Thus, it has been important to develop new medicines which target other key cytokines and immunologic pathways, including ustekinumab which inhibits both IL12 and IL23 and thus is felt to work in both the TH1 and TH7 pathways of inflammation, has been approved for the treatment of PsA as well as psoriasis. IL17 inhibitors, including secukinumab and ixekizumab have demonstrated significant effectiveness in psoriasis and PsA; abatacept, which modulates T cell activity via inhibition the second signal of T cell activation is under study. This article provides an historical overview of this revolution; details of specific biological therapies will be provided in adjacent articles in this supplement.

Publication types

  • Historical Article
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / history
  • Anti-Inflammatory Agents / therapeutic use*
  • Arthritis, Psoriatic / diagnosis
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Psoriatic / history
  • Arthritis, Psoriatic / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Biological Products / adverse effects
  • Biological Products / history
  • Biological Products / therapeutic use*
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / history
  • Inflammation Mediators / immunology
  • Remission Induction
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • Biological Products
  • Inflammation Mediators
  • Tumor Necrosis Factor-alpha