Publications

Highlights of 2019

Please click the links below to go to the CSF review of each paper

McInnes. I

2019 was another remarkable year in cytokine signalling. We can be optimistic that clinical practice for inflammatory arthritis will continue to improve, with promising long-term safety data supporting the use of established JAK inhibitors; tofacitinib and baricitinib, in addition to exciting phase III clinical data for filgotinib and newly approved upadacitinib. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respecti...

Keywords:

• Review

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

活動性関節リウマチ患者におけるバリシチニブ開始時の既 往歴や併存症に基づく有効性と安全性データ

Ann Rheum Dis. 2019 Aug;78(8):1135-1138.

Combe B,

Balsa A,

Sarzi-Puttini P,

Tony HP,

de la Torre I,

Rogai V,

Durand F,

Witt S,

Zhong J,

Dougados M

In a post-hoc analysis, BARI 4 mg showed similar efficacy and safety during placebo-controlled and LTE observation periods regardless of the presence or absence of select comorbidities in RA patients.Patients with RA have a high prevalence of comorbidities. This post-hoc analysis investigated the effect of select comorbidities (depression, osteoporosis, hepatic, cardiovascular or pulmonary disorders) on the efficacy and safety of BARI 4 mg QD in patients with moderate-to-severe active RA and ina...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Safety

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

活動性関節リウマチ患者におけるバリシチニブの中央値2年間の安全性

J Rheumatol. 2019 Jan;46(1):7-18. DOI: 10.3899/jrheum.171361

Smolen J,

Genovese M,

Takeuchi T,

Hyslop D,

Macias W,

Rooney T,

Chen L,

Dickson C,

Riddle Camp J,

Cardillo T,

Ishii T and Winthrop K

Baricitinib (BARI) showed an acceptable 5.5-year safety profile in this integrated analysis of patients with moderate-to-severe, active RA.This study evaluated the safety profile of the oral, once daily Janus kinase inhibitor, BARI, in adults with moderately to severely active RA. Data from eight randomised clinical trials and one long-term extension study were pooled and analysed for placebo comparison and dose response.There were 3492 patients who received BARI for a total of 6637 patient-yea...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Review

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

JAK Inhibition as a Therapeutic Strategy for Immune and Inflammatory Diseases

Nat Rev Drug Discov 2017;16:843–62 DOI: 10.1038/nrd.2017.201

Schwartz DM,

Kanno Y,

Villarino A,

Ward M,

Gadina M,

O’Shea JJ

Janus kinases (JAKs) are essential mediators of downstream signaling pathways in many inflammatory and autoimmune diseases. This review summarizes current clinical data on first- and second-generation JAK inhibitors (jakinibs) and discusses their use for the treatment of immune and inflammatory conditions.First generation jakinibs such as tofacitinib, baricitinib, and ruxolitinib, non-selectively inhibit JAK-dependent pro-inflammatory cytokines, which are major contributors to immunopathology. T...

Keywords:

• JAK,
• Review