JAK3-selective inhibitor peficitinib for the treatment of rheumatoid arthritis

Expert Rev Clin Pharmacol. 2019 Jun;12(6):547-554. doi: 10.1080/17512433.2019.1615443. Epub 2019 May 13.

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease characterized by synovitis as well as symmetric and destructive arthropathy. Although several disease modified antirheumatic-drugs (DMARDs) have widely used in clinical practice, certain patients are nonresponsive to or cannot take such medications due to adverse reactions. It is evident that Janus kinase (JAK) inhibitors have the potential to provide a significant breakthrough in the treatment of RA. These potent, orally administered, JAK inhibitors simplify the treatment options for patients. Areas covered: We discuss the pharmacodynamics, pharmacokinetics, efficacy, and safety of peficitinib for the treatment of RA. Expert opinion: Peficitinib is a novel JAK3 inhibitor potently inhibiting JAK3 enzymatic activity and JAK1/3-mediated cell proliferation. Its selectivity for JAK family kinases is similar to that of tofacitinib, but slightly less potent for JAK2. It is currently being evaluated by the FDA to treat adult patients with moderately to severely active RA who show inadequate response to or are intolerant of methotrexate. It can be used either as monotherapy or combination therapy with methotrexate, or other DMARDs. However, we think that more cautious consideration and measurement for adverse events are needed, after considering the safety results of ongoing clinical studies of peficitinib.

Keywords: JAK3-selective inhibitor; Janus kinase inhibitors; peficitinib; pharmacokinetics; rheumatoid arthritis.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology
  • Adamantane / therapeutic use
  • Adult
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / enzymology
  • Cell Proliferation / drug effects
  • Humans
  • Janus Kinase 3 / antagonists & inhibitors
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / pharmacology
  • Janus Kinase Inhibitors / therapeutic use*
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Niacinamide / therapeutic use
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use

Substances

  • Antirheumatic Agents
  • Janus Kinase Inhibitors
  • Piperidines
  • Pyrimidines
  • Pyrroles
  • Niacinamide
  • tofacitinib
  • JAK3 protein, human
  • Janus Kinase 3
  • peficitinib
  • Adamantane
  • Methotrexate