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

Tsutomu Takeuchi, Hisashi Yamanaka, Kunihiro Yamaoka, Shoko Arai, Shigeyuki Toyoizumi, Ryan DeMasi, Yuri Fukuma, Tomohiro Hirose, Naonobu Sugiyama, Samuel H. Zwillich, Yoshiya Tanaka

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)756-766
Number of pages11
JournalModern rheumatology
Volume29
Issue number5
DOIs
Publication statusPublished - 2019 Sep 1

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Methotrexate
Rheumatoid Arthritis
Clinical Trials
Safety
ametantrone
Placebos
tofacitinib

Keywords

  • Janus kinase
  • Japan
  • methotrexate
  • rheumatoid arthritis
  • tofacitinib

ASJC Scopus subject areas

  • Rheumatology

Cite this

Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose : A post hoc analysis of clinical trial data. / Takeuchi, Tsutomu; Yamanaka, Hisashi; Yamaoka, Kunihiro; Arai, Shoko; Toyoizumi, Shigeyuki; DeMasi, Ryan; Fukuma, Yuri; Hirose, Tomohiro; Sugiyama, Naonobu; Zwillich, Samuel H.; Tanaka, Yoshiya.

In: Modern rheumatology, Vol. 29, No. 5, 01.09.2019, p. 756-766.

Research output: Contribution to journalArticle

Takeuchi, T, Yamanaka, H, Yamaoka, K, Arai, S, Toyoizumi, S, DeMasi, R, Fukuma, Y, Hirose, T, Sugiyama, N, Zwillich, SH & Tanaka, Y 2019, 'Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: A post hoc analysis of clinical trial data', Modern rheumatology, vol. 29, no. 5, pp. 756-766. https://doi.org/10.1080/14397595.2018.1553489
Takeuchi, Tsutomu ; Yamanaka, Hisashi ; Yamaoka, Kunihiro ; Arai, Shoko ; Toyoizumi, Shigeyuki ; DeMasi, Ryan ; Fukuma, Yuri ; Hirose, Tomohiro ; Sugiyama, Naonobu ; Zwillich, Samuel H. ; Tanaka, Yoshiya. / Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose : A post hoc analysis of clinical trial data. In: Modern rheumatology. 2019 ; Vol. 29, No. 5. pp. 756-766.
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abstract = "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.",
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AU - Yamaoka, Kunihiro

AU - Arai, Shoko

AU - Toyoizumi, Shigeyuki

AU - DeMasi, Ryan

AU - Fukuma, Yuri

AU - Hirose, Tomohiro

AU - Sugiyama, Naonobu

AU - Zwillich, Samuel H.

AU - Tanaka, Yoshiya

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N2 - 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.

AB - 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.

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