Publications

分子標的療法に効果不十分の関節リウマチ患者における抗GM-CSFオチリマブ対サリルマブまたはプラセボ: フェーズ III 無作為化試験 (contRAst 3)

Ann Rheum Dis. 2023;82(12):1527–1537 doi 10.1136/ard-2023-224449

Taylor PC,

Weinblatt ME,

McInnes IB,

Atsumi T,

Strand V,

Takeuchi T,

Bracher M,

Brooks D,

Davies J,

Goode C,

Gupta A,

Makherjee S,

O’Shea C,

Saurigny D,

Schifano LA,

Shelton C,

Smith JE,

Wang M,

Watts S,

Fleischmann R

The ContRAst 3 study investigated otilimab, in RA patients with inadequate responses to multiple treatments. Otilimab did not significantly improve ACR20 versus placebo at Weeks 12 or 24. In addition, there we no significant improvements in secondary endpoints, including disease activity, disability, and pain.

Keywords:

• Sarilumab,
• Phase 3

従来型または生物学的抗リウマチ薬に効果不十分な関節リウマチ患者における抗GM-CSDオチリマブとプラセボとトファシチニブ (contRAst 1 と contRAst 2)

Ann Rheum Dis 2023;0:1–11 doi 10.1136/ard-2023-224482

Fleischmann R,

van der Heijde D,

Strand V,

Atsumi T,

McInnes I,

Takeuchi T,

Taylor P,

Bracher M,

Brooks D,

Davies J,

Goode C,

Gupta A,

Mukherjee S,

O’Shea C,

Saurigny D,

Schifano L,

Shelton C,

Smith J,

Wang M,

Wang R,

Watts S,

Weinblatt M

Fleischmann, et al investigated the safety and efficacy of otilimab versus tofacitinib and placebo in RA patients treated with MTX (contRAst 1) or csDMARDs (contRAst 2). They found that while otilimab achieved the primary endpoint of ACR20 versus placebo in Week 12, it did not demonstrate non-inferiority to tofacitinib.

Keywords:

• Phase 3,
• Tofacitinib

関節リウマチ患者におけるtofacitinibの深部血栓症　　リスク: 人口基盤のコホート研究

Rheumatology (Oxford). 2021 Mar 22:keab294. Epub ahead of print. DOI: 10.1093/rheumatology/keab294

Desai RJ,

Pawar A,

Khosrow-Khavar F,

Weinblatt ME,

Kim SC

A population-based cohort study of 87,653 RA patients has found no evidence for an increased risk of venous thromboembolism (VTE) for tofacitinib, versus TNFis, in patients with RA.The introduction of JAKinibs, almost a decade ago, has provided an important oral option for the treatment of RA. However, in recent years, a safety concern, relating to incidence of VTE after treatment, has emerged. Consequently, both the US and European regulatory authorities now recommend caution for use of tofacit...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Real-World

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

トファシチニブと腫瘍壊死因子阻害薬では同等の血栓塞栓症リスク: 関節リウマチ患者のコホート研究

Desai RJ, et al. Arthritis Rheumatol. 2019 June;71(6):892-900.

Desai RJ,

Pawar A,

Weinblatt ME,

Kim SC

Occurrences of venous thromboembolism (VTE) in 50, 865 RA patients initiating Tofacitinib (TOF) or a TNF inhibitor (TNFi) was infrequent. No significant risk of VTE for TOF versus TNFi was observed.Safety concerns of JAK inhibitor BARI include potentially increased risk of VTE at the higher 4 mg dose. It’s unclear if this is attributable to JAK-inhibition and extends to TOF. This study compared the risk of VTE with TOF, versus TNFi in real-world settings with RA patients.RA patients initiating T...

Keywords:

• JAK,
• Tofacitinib,
• Safety

関節リウマチ患者のトファシチニブ治療における　　　　　　　メトトレキサートまたはステロイドの中止または開始の効果: Post Hoc 解析

Rheumatol Ther 2018 Jun; 5(1):203–14. DOI: 10.1007/s40744-018-0093-7

Fleischmann R,

Wollenhaupt J,

Cohen S,

Wang L,

Fan H,

Bandi V,

Andrews J,

Takiya L,

Bananis E,

Weinblatt ME

Methotrexate (MTX) or Glucocorticoid (GC) discontinuation has little effect on CDAI response in patients given tofacitinib (TOF) for up to 3 years. Patients receiving TOF who showed initial improvements benefitted from initiation of MTX or GCs. Concomitant treatments such as MTX or GC are commonly used in combination with RA therapies to improve or accelerate clinical responses. However, their use is associated with many adverse events so clinicians aim to use them for a minimal duration.This po...

Keywords:

• JAK,
• Tofacitinib

Patient-reported Outcomes from a Phase 3 Study of Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis: Secondary Analyses from the RA-BEAM Study

Ann Rheum Dis 2017;76(11):1853-1861. doi: 10.1136/annrheumdis-2017-211259

Keystone EC,

Taylor PC,

Tanaka Y,

Gaich C,

DeLozier AM,

Dudek A,

Velasco Zamora J,

Covarrubias Cobos JA,

Rooney T,

de Bono S,

Arora V,

Linetzky B,

Weinblatt ME

This paper describes the patient-reported outcome (PRO) data collected in RA-BEAM, a Phase 3 study of baricitinib compared with both placebo and adalimumab in patients with RA and an inadequate response to MTX.PRO measures evaluated include health-related quality of life (HRQOL), physical function, disability, fatigue, sleep, mental health status, work productivity and work activity impairment. The RA-BEAM study demonstrated that patients treated with baricitinib experienced a greater improveme...

Keywords:

• JAK,
• Baricitinib,
• Phase 3,
• PRO / QoL

Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Arthritis Rheumatol 2016;68:2857–66

Genovese MC,

Smolen JS,

Weinblatt ME,

Burmester GR,

Meerwein S,

Camp HS,

Wang L,

Othman AA,

Khan N,

Pangan AL and Jungerwirth S

The summary and accompanying slide deck have been developed in conjunction with the Kremer et al. study (Study 2) which examined ABT-494 in TNF-IR patients in order to compare and contrast the data. In these two Phase 2b studies, ABT-494 (a novel selective JAK-1 inhibitor) was shown to be effective in patients with active RA who were non-responders to MTX or at least one TNF inhibitor.Patients with active RA who had an inadequate response to MTX (study 1) or were refractory to or intolerant of p...

Keywords:

• JAK,
• Updacitinib,
• Phase 2

A Randomized Phase 2b Study of ABT-494, a Selective JAK Inhibitor in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Arthritis Rheumatol 2016; Accepted article DOI 10.1002/art-39808 [Epub 2016]

Genovese M,

Smolen J,

Weinblatt M,

Burmester G,

Meerwein S,

Camp H,

Wang L,

Othman A,

Khan N,

Pangan A,

Jungerwirth S

This dose-ranging study evaluated the efficacy of the novel, selective JAK1 inhibitor ABT-494 versus placebo in patients with moderate-to-severe RA and inadequate response (IR) to MTX.In this 12-week, randomised, double-blind study (BALANCE II), the efficacy and safety ofABT-494 dosed at 3mg, 6 mg, 12 mg, 18 mg (all twice daily) and 24 mg (once daily) was assessed. Patients included had not received prior biologic therapy.Of the 299 patients included in the analysis, the proportions of patients ...

Keywords:

• JAK,
• Updacitinib,
• Phase 2

The Efficacy and Safety of Subcutaneous Clazakizumab in Patients with Moderate-to-Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results from a Phase IIb, Randomized, Double-Blind, Placebo/Active-Controlled, Dose-Ranging, Multinational Study

Arthritis & Rheumatology. 2015 Jul 2. doi: 10.1002/art.39249. [Epub ahead of print]

Weinblatt ME,

Mease P,

Mysler E,

Takeuchi T,

Drescher E,

Berman A,

Xing J,

Zilberstein M,

Banerjee S,

Emery P

The humanised monoclonal antibody, Clazakizumab (CLZ), binds to circulating interleukin-6 (IL-6) cytokine rather than the IL-6 receptor, blocking both classical and trans-signalling. The purpose of this phase 2B study was to evaluate the efficacy and safety of clazakizumab in patients with inadequate response to methotrexate (MTX). Data on selected response rates – ACR20/50/70, DAS28-CRP, SDAI ≤3.3, CDAI ≤2.8 and the ACR/EULAR Boolean definition – and adverse events were collected from 418 patie...