Model-Based Comparison of Dose-Response Profiles of Tofacitinib in Japanese Versus Western Rheumatoid Arthritis Patients

J Clin Pharmacol. 2020 Feb;60(2):198-208. doi: 10.1002/jcph.1514. Epub 2019 Sep 12.


Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The aim of this analysis was to characterize the relationship between tofacitinib dose and efficacy, as measured by American College of Rheumatology (ACR) response rates, and to compare this between Japanese and Western patients with RA. Efficacy data were pooled from 2 double-blind, dose-ranging phase 2 studies of tofacitinib monotherapy 1-15 mg twice daily in patients with RA with an inadequate response to disease-modifying antirheumatic drugs (DMARDs). NCT00550446 was carried out in mostly Western patients and NCT00687193 in Japanese patients. ACR20, ACR50, and ACR70 response rates in week 12 were analyzed using maximum drug effect (Emax ) models on the logit domain. Both studies showed a dose-response for each end point, supporting the efficacy of tofacitinib in patients with inadequate response to DMARDs. Study-specific differences in Emax were noted, whereas potency (dose providing half the maximum effect [ED50 ]) was similar across studies. After adjustment for study differences in Emax by calculating the fractions of the maximum placebo-adjusted proportion of ACR responses, the estimated locations for the 5- and 10-mg twice-daily doses on the dose-response curves were similar for the 2 patient populations: ACR20, ACR50, andACR70 mean fractional responses for 5 and 10 mg twice daily were 0.78, 0.43, 0.32 and 0.90, 0.69, and 0.56, respectively, for the Japanese study and 0.54, 0.41, and 0.22 and 0.73, 0.61, and 0.40, respectively, for the Western study. This analysis therefore supports the rationale for the same dosing regimen in Japanese patients as in Western patients from an efficacy perspective.

Keywords: Japanese; dose-response; efficacy; rheumatoid arthritis; tofacitinib.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / drug therapy*
  • Asian People
  • Black People
  • Clinical Trials, Phase II as Topic
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Multicenter Studies as Topic
  • Piperidines / administration & dosage*
  • Piperidines / pharmacokinetics*
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Pyrimidines / administration & dosage*
  • Pyrimidines / pharmacokinetics*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • White People
  • Young Adult


  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • tofacitinib

Associated data