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, Sadahiko; Toyoizumi, Shigeyuki; DeMasi, Ryan; Fukuma, Yuri; Hirose, Tomohiro; Sugiyama, Naonobu; Zwillich, Samuel H.; Tanaka, Yoshiya

doi:10.1080/14397595.2018.1553489

Cited by 11 publications

(3 citation statements)

References 34 publications

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“…This may be the result of the relatively higher proportion of Asian patients in the peficitinib clinical trials than in tofacitinib and baricitinib trials; due to the interaction between Asian ethnicity and the responses listed in the previous paragraph, the relative efficacy of peficitinib versus the other two JAK inhibitors was reduced once analyses were adjusted for the percentage of Asian patients. These results are consistent with data from previous trials, which showed that tofacitinib had greater efficacy in Asian patients than in [41,42]. We have also observed that peficitinib performed better in clinical trials in patients in Asian countries [9,10] compared with those in a global trial reported by Kivitz et al [43], despite the fact that patients in all three trials had had an inadequate response to MTX, and also predominantly moderate-tosevere RA according to baseline DAS28 or other validated composite measures of disease activity [9,10,43].…”

Section: Discussionsupporting

confidence: 92%

Comparative Efficacy and Safety of Peficitinib Versus Tofacitinib and Baricitinib for Treatment of Rheumatoid Arthritis: A Systematic Review and Network Meta-Analysis

Tanaka

Okumura

Kim³

et al. 2021

Rheumatol Ther

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Introduction: Peficitinib, a Janus kinase (JAK) inhibitor, is approved for clinical use in Japan, Korea, and Taiwan, but head-to-head comparisons versus other JAK inhibitors are lacking. We indirectly compared peficitinib, tofacitinib, and baricitinib for rheumatoid arthritis treatment. Methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congress archives up until February 12, 2019, for randomized controlled trials of peficitinib, tofacitinib, and baricitinib. Efficacy (American College of Rheumatology responses, disease activity scores, modified total Sharp score, Simplified Disease Activity Index [SDAI]) and safety outcomes were compared using a Bayesian network meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results. A network meta-regression assessed the impact on outcomes of proportions of patients receiving concomitant methotrexate or of Asian ethnicity. Results: The network meta-analysis included 21 randomized controlled trials. At 12 weeks, all evaluable efficacy outcomes were comparable or improved with peficitinib 150 mg and 100 mg once daily, versus baricitinib 2 and 4 mg once daily and tofacitinib 5 mg twice daily. At 24 weeks, efficacy outcomes were comparable or improved for each peficitinib dose versus baricitinib and tofacitinib. Risk of adverse events and serious adverse events at 12 weeks were similar with peficitinib 100 and 150 mg versus baricitinib and tofacitinib. The proportion of patients receiving concomitant methotrexate had no effect on any outcome analyzed, but Asian ethnicity had a positive effect on multiple efficacy outcomes. Conclusions: Peficitinib had comparable efficacy versus tofacitinib and baricitinib for

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Section: Discussionsupporting

confidence: 92%

Comparative Efficacy and Safety of Peficitinib Versus Tofacitinib and Baricitinib for Treatment of Rheumatoid Arthritis: A Systematic Review and Network Meta-Analysis

Tanaka

Okumura

Kim³

et al. 2021

Rheumatol Ther

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“…Post hoc analyses have suggested that concomitant MTX has minimal impact on efficacy, compared with bDMARD monotherapy (including adalimumab, etanercept, and infliximab) [22,23]. Assumptions regarding the impact of varying MTX dose on the efficacy and safety of bDMARDs or tsDMARDs in PsA may be drawn from post hoc analyses of RA studies [24][25][26]. For example, in a post hoc analysis of a phase III trial of tofacitinib in patients with RA, varying the MTX dose used in combination with tofacitinib had minimal effect on key endpoints, such as ACR and the Health Assessment Questionnaire-Disability Index (HAQ-DI) [25].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of tofacitinib by background methotrexate dose in psoriatic arthritis: post hoc exploratory analysis from two phase III trials

et al. 2021

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Objective Analyze tofacitinib efficacy and safety by background methotrexate (MTX) dose in patients with psoriatic arthritis (PsA). Methods This post hoc analysis pooled data from two phase III, double-blind trials (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) including patients receiving tofacitinib 5 or 10 mg twice daily (BID), or placebo, with stable MTX. Efficacy outcomes at month 3 stratified by MTX dose (≤ 15 month 3 stratified by MTX dose vs > 15 mg/week) were American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire-Disability Index (HAQ-DI); Psoriasis Area and Severity Index (PASI)50/75; change from baseline in HAQ-DI; physician’s global assessment of PsA (PGA-PsA-visual analog scale [VAS]); patient’s global joint and skin assessment (PGJS-VAS), Leeds Enthesitis Index (LEI); and Dactylitis Severity Score (DSS). Safety assessments included adverse events and laboratory parameters. Results Five hundred fifty-six patients received tofacitinib 5 mg BID (n = 186), 10 mg BID (n = 178), or placebo (n = 192), plus MTX (≤ 15 mg/week, n = 371; > 15 mg/week, n = 185). At month 3, tofacitinib efficacy was generally greater than placebo. Patients receiving tofacitinib 5 mg BID demonstrated greater numerical improvements in efficacy outcomes at month 3 with MTX > 15 mg/week vs MTX ≤ 15 mg/week; patients receiving tofacitinib 10 mg BID displayed the opposite. The safety profile was generally consistent between groups; headache was associated with MTX > 15 mg/week; decreased hemoglobin levels were observed in patients receiving tofacitinib 10 mg BID and MTX ≤ 15 mg/week. Conclusion Efficacy of tofacitinib was generally numerically greater than placebo, regardless of MTX dose. Tofacitinib 5 mg BID was generally more efficacious with MTX > 15 mg/week vs ≤ 15 mg/week; the opposite was observed for tofacitinib 10 mg BID. Headache was more frequent with MTX > 15 mg/week. Trial registration ClinicalTrials.gov. Identifier: NCT01877668 (registration: June 14, 2013) and NCT01882439 (registration: June 20, 2013). Key Points• Methotrexate is widely used in the treatment of psoriatic arthritis; however, there are limited data on the impact of varying background methotrexate doses on the efficacy and safety of Janus kinase inhibitors in patients with psoriatic arthritis.• This post hoc analysis assessed the impact of background methotrexate dose (≤ 15 or > 15 mg/week) on tofacitinib efficacy and safety in patients with psoriatic arthritis.• Results indicated that tofacitinib efficacy was generally numerically greater than placebo, regardless of methotrexate dose. Tofacitinib 5 mg twice daily, in combination with a higher dose of background methotrexate, was more efficacious compared with a lower dose of background methotrexate; the opposite was observed for tofacitinib 10 mg twice daily.• Headache was more frequent with the higher methotrexate dose. Data should be interpreted with caution due to the small sample sizes.

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“…Several randomized controlled trials (RCTs) in different countries have evaluated the efficacy of tofacitinib, baricitinib, peficitinib, upadacitinib, filgotinib and decernotinib as monotherapy in patients with RA by comparing them with placebo [3,[6][7][8][9][10], in which different JAK inhibitors showed better efficacy compared to placebo, but because the data from head-tohead studies comparing various JAK inhibitors at different doses are sparse, it is necessary to compare the efficacy of different JAK inhibitors at different doses in combination with evidence from RCTs of different treatments. Thie present study used a Bayesian reticulation meta-analysis to examine the relative efficacy and safety of various JAK inhibitors in RA patients.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of different Janus kinase inhibitors as monotherapy in rheumatoid arthritis: A Bayesian network meta-analysis

Qu,

Zhao,

Song

et al. 2024

PLoS ONE

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Objective This study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA. Methods The databases CNKI, VIP, Wanfang, CBM, and PubMed, Embase, Cochrane Library and Web of Science were searched to identify relevant randomized controlled trials (RCTs), all from the time of database creation to April 2024. Screening, data extraction, and risk of bias assessment (using Review Manager-5.3 software) were independently performed by at least two authors. The network meta-analysis was conducted using R 4.1.3 software. PROSPERO registration number: CRD42022370444. Results Thirty-three RCTs included 15,961 patients The experimental groups involved six JAK inhibitors (filgotinib, tofacitinib, decernotinib, baricitinib, upadacitinib and peficitinib) and 12 interventions (different doses of the six JAK inhibitors), and the control group involved adalimumab (ADA) and placebo. Compared with placebo, all JAK inhibitors showed a significant increase in efficacy measures (ACR20/50/70). Compared with ADA, only tofacitinib, low-dose decernotinib, and high-dose peficitinib showed a significant increase in ACR20/50/70. Decernotinib ranked first in the SUCRA ranking of ACR20/50/70. In terms of safety indicators, only those differences between low-dose filgotinib and high-dose upadacitinib, low-dose tofacitinib and high-dose upadacitinib were statistically significant. Low-dose filgotinib ranked first in the SUCRA ranking with adverse events as safety indicators. Only the efficacy and safety of tofacitinib ranked higher among different SUCRA rankings. Conclusion Six JAK inhibitors have better efficacy than placebo. The superior efficacy of decernotinib and safety of low-dose filgotinib can be found in the SUCRA. However, there are no significant differences in safety between the different JAK inhibitors. Head-to-head trials, directly comparing one against each other, are required to provide more certain evidence.

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

Cited by 11 publications

References 34 publications

Comparative Efficacy and Safety of Peficitinib Versus Tofacitinib and Baricitinib for Treatment of Rheumatoid Arthritis: A Systematic Review and Network Meta-Analysis

Comparative Efficacy and Safety of Peficitinib Versus Tofacitinib and Baricitinib for Treatment of Rheumatoid Arthritis: A Systematic Review and Network Meta-Analysis

Efficacy and safety of tofacitinib by background methotrexate dose in psoriatic arthritis: post hoc exploratory analysis from two phase III trials

The efficacy and safety of different Janus kinase inhibitors as monotherapy in rheumatoid arthritis: A Bayesian network meta-analysis

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