Clinical efficacy of new JAK inhibitors under development. Just more of the same?

Rheumatology (Oxford). 2019 Feb 1;58(Suppl 1):i27-i33. doi: 10.1093/rheumatology/key256.

Abstract

Janus kinase inhibition is promising in the treatment of RA, with already two oral drugs marketed. New compounds are under investigation that are more selective for Janus kinase 1 or Janus kinase 3. Phase II results for filgotinib, upadacitinib, peficitinib and decernotinib are reviewed showing almost consistently a fast dose-dependent clinical improvement similar to already approved drugs tofacitinib and baricitinib. I will reflect on the most frequently reported dose-dependent adverse events and laboratory changes. Some are similar for all drugs of this class, some are more specific for a certain drug, but all may influence future treatment effectiveness in daily practice. This implies the need for a critical evaluation of phase III trials, and eventually trials specifically powered for conclusions on the safety profile and registries once these drugs become marketed. These innovative drugs also need head-to-head trials versus biologics or in-class as well as specific strategy studies to determine their optimal future use.

Keywords: Janus kinase inhibitor; RA; decernotinib; filgotinib; peficitinib; upadacitinib.

Publication types

  • Review

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Azetidines / therapeutic use
  • Heterocyclic Compounds, 2-Ring / therapeutic use
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors
  • Janus Kinase 3 / antagonists & inhibitors
  • Janus Kinase Inhibitors / therapeutic use*
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Piperidines / therapeutic use
  • Purines
  • Pyrazoles
  • Pyridines / therapeutic use
  • Pyrimidines / therapeutic use
  • Pyrroles / therapeutic use
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Triazoles / therapeutic use
  • Valine / analogs & derivatives
  • Valine / therapeutic use

Substances

  • 2-((2-(1H-pyrrolo(2,3-b)pyridin-3-yl)pyrimidin-4-yl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide
  • Azetidines
  • GLPG0634
  • Heterocyclic Compounds, 2-Ring
  • Heterocyclic Compounds, 3-Ring
  • Janus Kinase Inhibitors
  • Piperidines
  • Purines
  • Pyrazoles
  • Pyridines
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • Triazoles
  • Niacinamide
  • upadacitinib
  • tofacitinib
  • Janus Kinase 1
  • Janus Kinase 3
  • Valine
  • peficitinib
  • baricitinib
  • Adamantane