Publications

JAK/STAT 経路: 関節リウマチの疼痛に焦点をあてて

Semin Arthritis Rheum. 2021 Feb;51(1):278-284

Simon LS,

Taylor PC,

Choy EH,

Sebba A,

Quebe A,

Knopp KL,

Porreca F

Many cytokines associated with RA pathogenesis and pain are affected directly or indirectly by the JAK/STAT pathway, therapeutic targeting may offer promise. Having better understanding of these mechanisms can help clinicians make treatment decisions that optimise the control of inflammation and pain. However, pain in patients with RA is complex and involves multiple driving mechanisms that may differentially occur over time in different people. Although one known constant is that nociceptive ac...

Keywords:

• JAK,
• Basic Science,
• Review

関節リウマチに対するトファシチニブの有害事象として出現したIgA 血管炎

Intern Med. 2020;59(6):817-821

Itoh I,

Kasuno K,

Yamamoto C,

Takahashi N,

Shimizu H,

Ojima T,

Hayashi S,

Kimura H,

Iwano M

Nephrotoxicity is a key side effect of NSAIDs and DMARDs used to treat RA, while biologics can reportedly cause proliferative glomerulonephritis or crescentic glomerulonephritis. This report reviews a patient on TOF presenting IgA vasculitis as an adverse effect that fully resolved following termination of TOF.Drug induced IgA vasculitis has been previously described for anti-TNFɑ therapies, but this is the first report with JAK inhibitor therapy. This is a case report of a 67-year old woman wit...

Keywords:

• JAK,
• Tofacitinib,
• Safety

関節リウマチ患者におけるMTX併用Tofacitinib: 24か月間の フェーズ3 ORAL Scan試験からの患者報告アウトカム結果

Clin Exp Rheumatol . Sep-Oct 2020;38(5):848-857. Epub 2019 Dec 19.

Strand V,

van der Heijde D,

Tanaka Y,

Keystone E,

Kremer J,

Zerbini C A F,

Cardiel M H,

Cohen S,

Nash P,

Song Y-W,

Tegzová D,

Gruben D,

Wallenstein G,

Connell C A,

Fleischmann R

In the ORAL SCAN study, patients receiving TOF 5 mg or 10 mg BID reported significant improvements in patient-reported outcomes at month 3 compared with placebo, which were maintained through 24 months of treatment.RA causes a significant health and socioeconomic burden and affects all aspects of health related quality of life. ORAL Scan included patients with active RA and inadequate response to MTX who were randomised to receive TOF 5 mg or 10 mg BID plus MTX or PBO. This study evaluated the i...

Keywords:

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

患者報告アウトカムに対するUpadacitinibの効果: SELECT-BEYOND, 生物学的製剤に効果不十分な関節リウマ チ患者を対象とした無作為化フェーズ3試験, からの結果

Arthritis Res Ther . 2019 Dec 2;21(1):263. doi: 10.1186/s13075-019-2059-8.

Strand V,

Schiff M,

Tunida N,

Friedman A,

Meerwein S,

Pangan A,

Ganguli A,

Fuldeore M,

Song Y,

Pope J

In SELECT-BEYOND, UPA demonstrated clinically meaningful improvements in patient reported outcomes compared to PBO in patients with RA who had an inadequate response to bDMARDs. In this post-hoc analysis of the SELECT-BEYOND study, the effect of UPA 15 or 30 mg on patient reported outcomes were assessed and compared to PBO.Eligible patients (498) with an inadequate response to bDMARDs were randomly assigned 1:1:1 to receive UPA 15 mg, UPA 30 mg or PBO. PROs collected at Wk1, Wk4, and Wk12 includ...

Keywords:

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

Upadacitinib は従来型抗リウマチ薬が効果不十分な関節 リウマチ患者の患者報告アウトカムを改善する: SELECT-NEXT 試験結果

Arthritis Res Ther . 2019 Dec 9;21(1):272.

Strand V,

Pope J,

Tundia N,

Friedman A,

Camp H,

Pangan A,

Ganguli A,

Fuldeore M,

Goldschmidt D,

Schiff M

In SELECT-NEXT, UPA demonstrated clinically meaningful improvements in patient reported outcomes compared to PBO in patients with RA who had an inadequate response to csDMARDs. In this post hoc analysis, the effect of UPA 15 or 30 mg on patient reported outcomes were assessed and compared to PBO.Eligible patients (661) with an inadequate response to csDMARDs were randomly assigned 2:2:1:1 to receive background csDMARD therapy with either UPA 15 mg, UPA 30 mg or PBO. PROs collected at Wk4 and Wk1...

Keywords:

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

低疾患活動性のRA患者における疼痛緩和と機能改善に対するバ リシチニブとアダリムマブの効果: RA-BEAMからの探索的解析

J Clin Med. 2019 Sep 5;8(9). pii: E1394

Fautrel B,

Kirkham B,

Pope JE,

Takeuchi T,

Gaich C,

Quebe A,

Zhu B,

de la Torre I,

De Leonardis F,

Taylor PC

Post hoc analyses from RA-BEAM concluded that BARI 4 mg QD or ADA 40 mg Q2W resulted in improvements in pain, physical function, fatigue and work productivity in patients with RA, independent of the treatment’s impact on inflammation. Among patients achieving remission or LDA, greater improvements in pain and physical function were seen with BARI than with ADA or PBO.Of 1010 patients included in the analysis at Week 24, 168 were in remission, 310 were in remission/LDA and 700 were not in remissi...

Keywords:

• JAK,
• Baricitinib,
• Phase 3,
• Pain

メトトレキサートに効果不十分な関節リウマチ患者における Upadacitinib 対 Placebo または Adalimumab : フェーズ3, 二 重盲検, 無作為化対照試験結果

Arthritis Rheumatol 2019 DOI: 10.1002/art.41032

Fleischmann R,

Pangan AL,

Song IH,

Mysler E,

Bessette L,

Peterfy C,

Durez P,

Ostor AJ,

Li Y,

Zhou Y,

Othman AA,

Genovese MC

UPA demonstrated superiority to ADA in terms of clinical, functional and patient-reported outcomes with comparable radiographic inhibition. As many RA patients fail to achieve LDA and remission with TNF inhibitors and MTX there is a requirement for additional treatment options. In this SELECT-COMPARE study the clinical and functional outcomes of UPA were compared to ADA in MTX-IR patients. 1629 MTX-IR were randomly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W or PBO, with background MTX. Key end...

Keywords:

• JAK,
• Updacitinib,
• Phase 3

反応性不良または試験デザインのためアダリムマブからバリシチニブにスイッチした患者の臨床的アウトカム: RA患者を対象とした第３相試験

Ann Rheum Dis. 2019 Jul;78(7):890-898.

Tanaka Y,

Fautrel B,

Keystone EC,

Ortmann RA,

Xie L,

Zhu B,

Issa M,

Patel H,

Gaich CL,

de Bono S,

Rooney TP,

Taylor PC

Switching from ADA to BARI without a lengthy washout period can be executed with acceptable safety and tolerability and was associated with maintained disease control. Switching therapies in RA is commonplace in myriad scenarios including inadequate responses, intolerances and patient preference. Assessing the safety and efficacy of new treatments such as BARI, in the context of use as a replacement therapy, is beneficial. A previous study (RA-BEACON) has demonstrated that safely switching from ...

Keywords:

• JAK,
• Baricitinib,
• Phase 3

Efficacy and Safety of Filgotinib, a Selective Janus Kinase 1 Inhibitor, in Patients with Active Psoriatic Arthritis (EQUATOR): Results from a Randomised, Placebo-controlled, Phase 2 Trial

Lancet. 2018 Dec 1;392(10162):2367-2377. DOI 10.1016/ S0140-6736(18)32483-8

Mease P,

Coates LC,

Helliwell PS,

Stanislavchuk M,

Rychlewska-Hanczewska A,

Dudek A,

Abi-Saab W,

Tasset C,

Meuleners L,

Harrison P,

Besuyen R,

Van der Aa A,

Mozafarian N,

Greer JM,

Kunder R,

Van den Bosch F,

Gladman DD

In this first clinical trial of filgotinib in patients with PsA, filgotinib was effective in treating the signs and symptoms of active PsA across various disease manifestations.The EQUATOR trial was a randomized, double-blind, placebo-controlled, Phase 2 trial, that enrolled 191 adult patients from 25 sites in seven countries. Patients with active moderate-to-severe PsA and an insufficient response or intolerance to at least one csDMARD were assigned 1:1 to receive filgotinib 200 mg or placebo o...

Keywords:

• JAK,
• Filgotinib,
• Phase 2

RAPID3による，トファシチニブ治療関節リウマチ患者の疾患活動性評価: 2つのフェーズ3治験の事後解析

Clin Rheumatol 2018 Aug; 37(8):2043–53

Strand V,

Lee EB,

Yazici Y,

Dikranian A,

Wilkinson B,

Takiya L,

Zang C,

Bananis E,

Bergman MJ

Patients given tofacitinib (TOF) who achieved Routine Assessment of Patient Index Data 3 (RAPID3) remission or low disease activity (LDA) at 6 months, had improved long-term outcomes at 2 years, compared to patients with moderate or high disease activity (MDA/HDA) at 6 months.RAPID3¹ is a patient-reported evaluation of disease activity, based on pooled PROs; patient global assessment, patient assessment of arthritic pain and HAQ-DI scores. Previous studies with tocilizumab have suggested that RA...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3