Publications

関節リウマチ治療における中央値3年にわたるBaricitinibの 安全性プロファイル: 安全性解析のアップデート

Lancet Rheumatol 2020;2:e347–57

Genovese MC,

Smolen JS,

Takeuchi T,

Burmester G,

Brinker D,

Rooney TP,

Zhong J,

Daojun M,

Saifan C,

Cardoso A,

Issa M,

Wu W-S,

Winthrop KL

RA is a chronic, life-long disease requiring long-term treatment. As such, it is important to understand the long-term safety profile of DMARDs. In this analysis, baricitinib maintained a stable safety profile during long-term exposure. This baricitinib safety analysis included integrated data from nine Phase 3, 2, and 1b clinical trials, and one long-term extension, with data up to 360 weeks. 3700 patients were included, with maximum follow-up of almost 7 years – representing an additional 3,54...

Keywords:

• JAK,
• Baricitinib,
• Safety

RA診療におけるEULAR推奨– 2019 アップデートとJAK阻害薬に関する共同声明

Ann Rheum Dis. 2020 Jan 22. pii: annrheumdis-2019-216655.

Smolen JS,

Landewé RBM,

Bijlsma JWJ,

Burmester GR,

Dougados M,

Kerschbaumer A,

McInnes IB,

Sepriano A,

et al.

The EULAR recommendations for the management of RA have become increasingly useful in providing rheumatologists, patients, payers and other stakeholders with the evidence-based guidance and views of experts on the optimal use and sequence of pharmaceutical therapies in patients with RA. Over the course of the last decade, the evolution of the treatment landscape has already required two updates. The release of the new addition updates the 2016 recommendations.An international task force consider...

Keywords:

• EULAR

関節リウマチ患者におけるトファシチニブのフェーズIIIと長期 試験での, 主要な心血管有害事象のリスク因子

Arthritis Rheumatol .2019 Sep;71(9):1450-1459. doi: 10.1002/art.40911. Epub 2019 Aug 6.

Christina Charles-Schoeman,

Ryan DeMasi,

Hernan Valdez,

Koshika Soma,

Lie-Ju Hwang,

Mary G. Boy,

Pinaki Biswas,

Iain B. McInnes

Post hoc analyses of the six ORAL studies and two LTE’s suggested that after 24 weeks of TOF treatment, increases in HDL-c and decreases in the TC/HDL-c ratio appeared to be associated with reduced future MACE risk in RA patients. 52 MACE occurred in 4076 patients over 12873 patient-years of exposure. Separate Cox regression models were used to evaluate traditional CV risk factors’ association with time to first MACE at baseline and changes in lipid levels with time to future MACE after 24 weeks...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• LTE,
• Cardiovascular

トファシチニブで治療された乾癬性関節炎患者の脂質変化と心血 管イベント発生率: フェーズ3と長期試験のプール解析

Arthritis Care Res (Hoboken) 2019;71(10):1387–95

Gladman DD,

Charles-Schoeman C,

McInnes IB,

Veale DJ,

Thiers B,

Nurmohamed M,

Graham D,

Wang C,

Jones T,

Wolk R,

DeMasi R

Serum lipid level increases at month 3 following TOF treatment in PsA were consistent with observation in RA and psoriasis. The risk of CV disease is higher in people with PsA versus the general population – comparable with the well-documented rates seen in RA and diabetes. The reasons for this are not fully elucidated, but it has been suggested that there is an association between peripheral joint inflammation and lipid dysregulation in PsA. This post hoc analysis of pooled data from OPAL Broad...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• Safety,
• LTE,
• Cardiovascular

ヤヌスキナーゼ阻害薬が関節リウマチ患者の心血管イベントに及ぼすリスク: 無作為化試験のシステマティックレビューとメタ解析

Ann Rheum Dis. 2019 Aug;78(8):1048-1054.

Xie W,

Huang Y,

Xiao S,

Sun X,

Fan Y,

Zhang Z

Existing evidence from RCTs indicated no significant change in CV risk for JAK inhibitor (JAKinib) treated RA patients in a short-term perspective compared to placebo.Patients with RA have an elevated risk of CV morbidity and mortality, which cannot be fully explained by traditional CV risk factors. Reaching remission or LDA in order to reduce CV events (CVE) is encouraged in the current EULAR recommendations. JAKinibs and their roles in the modulation of CV risk remain undetermined. This study ...

Keywords:

• JAK,
• Safety,
• Meta analysis,
• Cardiovascular

関節リウマチ治療における，Tofacitinib の 9.5年間の有効性 と安全性: グローバル，オープンラベル，長期延長試験の最 終結果

Arthritis Res Ther. 2019 Apr 5;21(1):89.

Wollenhaupt J,

Lee EB,

Curtis JR,

Silverfield J,

Terry K,

Soma K,

Mojcik C,

DeMasi R,

Strengholt S,

Kwok K,

Lazariciu I,

Wang L,

Cohen S

TOF 5 mg and 10mg BID demonstrated a consistent safety profile and sustained efficacy for up to 9.5 years in this open-label LTE ORAL Sequel study.TOF 5 mg and 10 mg BID demonstrated consistent safety (as monotherapy and combination therapy) and efficacy within this open-label LTE study of RA patients. As RA requires long-term treatment, it’s important to assess the long-term efficacy and safety of RA therapies to understand the potential lifelong impact on patient health and quality of life. Th...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Efficacy,
• LTE

バリシチニブは関節リウマチにおいてLDL-C と HDL-C 上昇を誘導する: 無作為化対照比較試験のメタ解析

Lipids Health Dis. 2019 Feb 18;18(1):54.

Qiu C,

Zhao X,

She L,

Shi Z,

Deng Z,

Tan L,

Tu X,

Jiang S,

Tang B

This study confirmed that BARI induced a stable dose-dependent increase in LDL-C and HDL-C levels. There was no significant difference of CV risk between BARI and placebo groups.High risk of CV events is strongly associated with RA. Mechanisms underlying the excess risk of CV events in RA remains unclear. This study aims to provide additional insight into the clinical safety of BARI, focusing on the effects of BARI on LDL-C and HDL-C levels and CV risk. A Cochrane analysis was performed on studi...

Keywords:

• JAK,
• Baricitinib,
• Meta analysis,
• Cardiovascular

関節リウマチにおけるバリシチニブの心血管に対する安全性

Arthritis Rheumatol. 2019 Jul;71(7):1042-1055.

Taylor PC,

Weinblatt ME,

Burmester GR,

Rooney TP,

Witt S,

Walls CD,

Issa M,

Salinas CA,

Saifan C,

Zhang X,

Cardoso A,

González-Gay MA,

Takeuchi T

This study indicates no association between exposure to BARI and MACE, arterial thrombotic events (ATE), or congestive heart failure (CHF). Overall IRs for venous thromboembolic event (VTE) in BARI-treated patients falls within the reported range for patients with RA.RA patients have a greater risk of cardiovascular (CV) diseases of arterial ischemic origin, and an increased risk of VTE. Studied frequencies of thromboembolic events in RA populations in the last decade has been reported as 2–3x h...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Cardiovascular

バリシチニブ試験フェーズ IIとIIIにおける脂質プロファイルとスタチン治療の影響

Ann Rheum Dis. 2018 Jul;77(7):988-995. DOI 10.1136/annrheumdis-2017-212461

Taylor PC,

Kremer JM,

Emery P,

Zuckerman SH,

Ruotolo G,

Zhong J,

Chen L,

Witt S,

Saifan C,

Kurzawa M,

Otvos JD,

Connelly MA,

Macias WL,

Schlichting DE,

Rooney TP,

de Bono S,

McInnes IB

Baricitinib (BARI) was associated with increased lipid levels; baseline statins did not alter these profiles. The introduction of statins during treatment reduced total cholesterol and LDL-C.The use of anti-inflammatory drugs in RA patients has been shown to alter lipid levels and is associated with reduced atherogenic risk. Increases in lipid levels, specifically HDL-C and LDL-C, have been observed in Phase 2 BARI studies1.This study analysed data from seven randomised RA Phase 2/3 studies of ...

Keywords:

• JAK,
• Baricitinib,
• Phase 3,
• Safety,
• Cardiovascular

Effects of Tofacitinib and other DMARDs on Lipid Profiles in Rheumatoid Arthritis: Implications for the Rheumatologist

Semin Arthritis Rheum 2016;46:71–80

Charles-Schoeman et al.

Increased inflammation and CV disease have been associated with lower total cholesterol (TC) and low density lipoprotein (LDL-C) levels in RA patients – an apparent paradox to what is observed in the general population. Previously, reduced high-density lipoprotein (HDL-C) levels have been associated with increased risk of CV, and an inverse relationship observed with levels of HDL-C level and C-reactive protein (CRP).This analysis of the literature with regard to studies using DMARDs in RA patie...

Keywords:

• JAK,
• Tofacitinib,
• Cardiovascular