Publications

活動性関節リウマチ患者におけるPeficitinib 25, 50, 100, 150 mgの 有効性と安全性の比較: ランダム化対照試験のBayesian Network Meta-Analysis

Clin Drug Investig .2020 Jan;40(1):65-72. doi: 10.1007/s40261-019-00863-9.

Lee YH,

Song GG

PEF 50, 100, and 150 mg once daily was effective in treating active RA, without causing a significant risk for AEs.Intracellular pathways, including JAK and Tyk-2, are critical for immune cell activation, pro-inflammatory cytokine production, and cytokine signaling. PEF has been developed for use in RA, but the comparative efficacy and safety of regimens and dosages has not been established. A Bayesian network meta-analysis was conducted to combine direct and indirect evidence to assess the rela...

Keywords:

• JAK,
• Peficitinib,
• Meta analysis

関節リウマチにおける低分子JAK阻害薬の感染リスクに関す るシステマティックレビューとメタ解析

Rheumatology (Oxford) 2019;58(10):1755–66

Bechman K,

Subesinghe S,

Norton S,

Atzeni F,

Galli M,

Cope AP,

Winthrop KL,

Galloway JB

Absolute serious infection rates were low. However, across the JAKinibs, the incidence of HZ is higher than expected for the population. While the risk was numerically greatest with BARI, indirect comparisons between the drugs did not demonstrate any significant difference in risk. How JAKinibs increase the risk of HZ reactivation is unclear, but how different JAKs interact in the immune response suggest that there may be differences in safety profiles between JAKinib drugs, underpinned by their...

Keywords:

• Safety,
• 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

Baricitinib, Upadacitinib および Tofacitinib を介したヒト白血球 分画におけるサイトカインシグナルの比較

Arthritis Res Ther. 2019 Aug 2;21(1):183

McInnes IB,

Byers NL,

Higgs RE,

Lee J,

Macias WL,

Na S,

Ortmann RA,

Rocha G,

Rooney TP,

Wehrman T,

Zhang X,

Zuckerman SH,

Taylor PC

Different JAKinibs modulated distinct cytokine pathways to varying degrees, and no agent potently or continuously inhibited an individual cytokine signalling pathway throughout the dosing interval. This study aimed to compare the in vitro cellular pharmacology of BARI, TOF and UPA across relevant leukocyte subpopulations, coupled with their in vivo PK, to determine their effects on distinct cytokine pathways. Peripheral blood mononuclear cells from healthy donors were incubated with different JA...

Keywords:

• JAK,
• Baricitinib,
• Tofacitinib,
• Upadacitinib,
• MOA

メソトレキセートに効果不十分の関節リウマチ患者におけるPeficitinib (ASP015K) の有効性と安全性: 日本で実施された Phase III 無作 為化二重盲検プラセボ対照臨床試験結果 (RAJ4)

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215164

Takeuchi T,

Tanaka Y,

Tanaka S,

Kawakami A,

Iwasaki M,

Katayama K,

Rokuda M,

Izutsu H,

Ushijima S,

Kaneko Y,

Shiomi T,

Yamada E,

van der Heijde D

Peficitinib (PEF) 100 and 150 mg demonstrated robust clinical and structural efficacy in patients with RA who have an inadequate response to MTX. In Japan, two JAK inhibitors, TOF and BARI are currently available for RA patients with an inadequate response to conventional therapies. This randomized phase 3 study (RAJ4), assessed the efficacy and safety of two PEF doses in combination with MTX compared to PBO, in Japanese MTX-IR. Patients were randomized 1:1:1 to PBO, PEF 100 mg and 150 mg with M...

Keywords:

• JAK,
• Peficitinib,
• Phase 3

抗リウマチ薬に抵抗性の中等度から重度関節リウマチ患者に おける臨床的反応性に対する Filgotinib の Placebo対照とした 効果 : FINCH 2 無作為化試験

JAMA 2019 322(4):315-325

Genovese MC,

Kalunian K,

Gottenberg JE,

Mozaffarian N,

Bartok B,

Matzkies F,

Gao J,

Guo Y,

Tasset C,

Sundy JS,

de Vlam K,

Walker D,

Takeuchi T

Among RA patients with an inadequate response or intolerance to bDMARDs, filgotinib (FIL) doses, compared to PBO resulted in significantly greater proportions achieving a clinical response at Wk12.Patients with active RA despite treatment with bDMARD therapy need treatment options. The FINCH 2 Phase 3 study compared the effects of FIL vs PBO for the treatment of RA patients with inadequate response or intolerance to ≥1 prior bDMARDs. Patients were randomized in a 1:1:1 ratio, receiving FIL 200 m...

Keywords:

• JAK,
• Filgotinib,
• Phase 3

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,
• Upadacitinib,
• Phase 3

関節リウマチ患者におけるメトトレキサート併用下かつ効果 不十分例でスイッチした際のUpadacitinib または Adalimumab の48週安全性と有効性

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215764

Fleischmann RM,

Genovese MC,

 Enejosa JV,

 Mysler E,

Bessette L,

Peterfy C,

 Ostor P,

 Li Y,

 Song I

Consistent with Wk26 data, significantly more UPA patients achieved LDA and remission versus ADA and PBO over 48 weeks. RA patients often change therapy due to inadequate response and intolerance. The SELECT COMPARE study was designed to explore switching to JAK inhibitors from TNF inhibitors without a wash-out period (and vice versa). The long-term safety and efficacy of UPA was compared to ADA and PBO in MTX-IR.1629 patients were blindly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W and PBO, wi...

Keywords:

• JAK,
• Upadacitinib,
• Phase 3

メトトレキサート併用または非併用トファシチニブ，またはメトトレキサート併用アダリムマブ治療中の関節リウマチ患者における帯状疱疹生ワクチン

Arthritis Care and Research 2019 DOI: 10.1002/acr.24010

Calabrese LH,

Abud-Mendoza C,

Lindsey SM,

Lee SH,

Tatulych S,

Takiya L,

Iikuni N,

Soma K,

Luo Z,

Fleischmann R

Live zoster vaccine (LZV) was well tolerated, and herpes zoster (HZ) incidence rates were generally similar between treatment groups in vaccinated versus non-vaccinated patients in a subset of RA who received LZV before TOF ± MTX, or ADA + MTX, in ORAL Strategy. It is known that patient with RA are at increased risk of developing HZ though the mechanisms behind this are currently not well understood though therapies, such as TOF, are thought to increase the risk. ACR and EULAR recommend using LZ...

Keywords:

• JAK,
• Tofacitinib,
• Vaccination