Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: A post hoc analysis of clinical trial data

Mod Rheumatol. 2019 Sep;29(5):756-766. doi: 10.1080/14397595.2018.1553489. Epub 2019 Jan 11.


Objectives: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We investigated concomitant methotrexate (MTX) dose on tofacitinib efficacy/safety in Japanese RA patients. Methods: This post hoc analysis pooled data from a 3-month phase 2 study (NCT00603512) and a 24-month phase 3 study (NCT00847613). Patients (N= 254) received tofacitinib (low-dose (1 or 3 mg), 5 mg, 10 mg) twice daily (BID) or placebo, with low-dose (>0 to 8 mg/week) or high-dose (>8 mg/week) MTX. Efficacy (ACR20/50/70 and DAS28-4 (ESR)<2.6 response rates; changes from baseline (CFB) in DAS28-4 (ESR) and HAQ-DI) and safety (adverse events (AEs), discontinuations due to AEs, serious AEs, and deaths) were assessed through month 3. Results: At month 3, ACR20/50/70 response rates, mean DAS28-4 (ESR) CFB and HAQ-DI CFB were similar across MTX doses and generally greater for all tofacitinib doses versus placebo. AE rates with low-dose/high-dose MTX were: placebo, 28.6%/52.9%; tofacitinib low-dose, 50.0%/66.7%; 5 mg BID, 56.5%/64.3%; 10 mg BID, 73.8%/67.7%. Conclusion: Tofacitinib efficacy in Japanese RA patients may be unaffected by background MTX dose. AE rates with low-dose versus high-dose MTX were lower with placebo, tofacitinib low-dose or 5 mg BID, but not 10 mg BID, with no apparent differences across system organ class/laboratory parameters.

Keywords: Janus kinase; Japan; methotrexate; rheumatoid arthritis; tofacitinib.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Piperidines / administration & dosage
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*


  • Antirheumatic Agents
  • Piperidines
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • Methotrexate