Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies

Int J Rheum Dis. 2016 Dec;19(12):1216-1225. doi: 10.1111/1756-185X.12901. Epub 2016 Jul 25.

Abstract

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1-30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore, the efficacy and safety of tofacitinib 5 and 10 mg twice daily in Phase 2 studies are the focus of this review. Tofacitinib ≥ 5 mg twice daily was efficacious in a dose-dependent manner, with statistically significant and clinically meaningful reductions in the signs and symptoms of RA and patient-reported outcomes. The safety profile was consistent across studies. The efficacy and safety profile of tofacitinib in Phase 2 studies supported its further investigation and the selection of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily for evaluation in Phase 3 studies.

Keywords: Phase 2; efficacy; rheumatoid arthritis; safety; tofacitinib.

Publication types

  • Review

MeSH terms

  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / enzymology
  • Clinical Trials, Phase II as Topic
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Janus Kinases / antagonists & inhibitors*
  • Janus Kinases / metabolism
  • Male
  • Middle Aged
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Randomized Controlled Trials as Topic
  • Remission Induction
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • Janus Kinases