Publications

デンマークとスウェーデンの関節リウマチ患者におけるアバタセプト，リツキシマブおよびトシリズマブを実臨床の重篤有害事象リスク

Ann Rheum Dis. 2019 Mar;78(3):320-327. DOI: 10.1136/annrheumdis-2018-214326

Grøn KL,

Arkema EV,

Glintborg B,

Mehnert F,

Østergaard M,

Dreyer L,

Nørgaard M,

Krogh NS,

Askling J,

Hetland ML; ARTIS Study Group

Differences in baseline characteristics and numerical differences in IR of SI between ABA, RRTX and TOZ were observed. The relative risk (RR) of SIs seemed to vary modestly with drug.TNFi treated RA patients in large observational studies have suggested an initial twofold increased risk of SIs compared with biologic-naïve patients. Long-term observational studies on the risk of SIs in patients treated with non-TNFi bDMARDs are sparse.This study aimed to estimate crude as well as age and gender-a...

Keywords:

• Abatacept,
• Tocilizumab,
• Infections

トシリズマブ、アバタセプト、トファシチニブで治療中の関節リウマチ患者におけるC型肝炎ウイルス複製の比較

Ann Rheum Dis. 2019 Jun;78(6):849-850.

Chen YM,

Huang WN,

Liao TL,

Chen JP,

Yang SS,

Chen HH,

Hsieh TY,

Hung WT,

Chen YH,

Chen DY

Tocilizumab (TCZ), abatacept (ABA) and tofacitinib (TOF) appear to have no major safety concerns for treatment of RA patients with hepatitis C virus (HCV) infections.HCV is an infectious disease which continues to present a major therapeutic challenge for clinicians in treating patients with RA. Previous reports demonstrate that the use of TNF targeted therapies in RA patients with HCV infections appear to have no major safety concerns. During short-term therapy with TCZ and ABA, data has shown ...

Keywords:

• Tofacitinib,
• Tocilizumab,
• Abatacept,
• Infections

Characterization and Changes of Lymphocyte Subsets in Baricitinib-Treated Patients With Rheumatoid Arthritis: An Integrated Analysis.

Arthritis Rheumatol. 2018 Dec;70(12):1923-1932. doi: 10.1002/art.40680

Tanaka Y,

McInnes IB,

Taylor PC,

Byers NL,

Chen L,

de Bono S,

Issa M,

Macias WL,

Rogai V,

Rooney TP,

Schlichting DE,

Zuckerman SH,

Emery P

This review shows that changes in lymphocyte subsets were largely within normal reference ranges and were not associated with efficacy or safety end points. BARI is a selective JAK1/JAK2 inhibitor, approved for the treatment of moderate to severe RA. BARI treatment is associated with changes to circulating lymphocyte and lymphocyte subsets, however detailed analyses of these effects, and their relevance to efficacy and safety is lacking. This study investigated the changes in lymphocyte cell sub...

Keywords:

• JAK,
• Baricitinib,
• Basic Science,
• MOA

関節リウマチ患者におけるトファシチニブのリンパ球に対する短期、中期、長期的影響

Arthritis Rheumatol 2018 DOI: 10. 1002/art.40780

van Vollenhoven R,

Lee EB,

Strengholt S,

Mojcik C,

Valdez H,

Krishnaswami S,

Biswas P,

Lazariciu I,

Hazra A,

Clark JD,

Hodge J,

Wang L,

Choy E

Tofacitinib (TOF) treatment is associated with short-term transient increases in absolute lymphocyte counts (ALC), followed by a gradual decline to reach steady state by ~48 months. Changes in both ALC and lymphocyte subset counts (LSC) were reversible upon TOF discontinuation. Low ALC but not LSC were associated with an increased risk of serious infective episodes (SIEs) and herpes zoster (HZ). This data supported the treatment recommendations on ALC counts for starting and continuing therapy w...

Keywords:

• JAK,
• Tofacitinib,
• MOA

トファシチニブ使用時の帯状疱疹は、グルココルチコイド併用でさらに増加するが、メソトレキセートでは増加しない

Arthritis Care Res 2018 DOI 10.1002/acr.23769

Curtis JR,

Xie F,

Yang S,

Bernatsky S,

Chen L,

Yun H,

Winthrop K

The rate of Herpes Zoster (HZ) in tofacitinib (TOF) users with concomitant glucocorticoids (GC) was approximately double that of other TOF combination therapies.TOF is an effective treatment for RA. Increased HZ risk has been observed with the use of JAK inhibitors, whereas the HZ risk with biologics and targeted RA therapies are comparable. This study evaluated the HZ risk in TOF users according to concomitant GC, MTX, both, or neither. MarketScan and Medicare data were used to identify 8030 rh...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Infections

疾患が持続的にコントロールされた関節リウマチ患者におけるバリシチニブ減量: プロスペクティブコホート

Ann Rheum Dis. 2019 Feb;78(2):171-178. DOI 10.1136/annrheumdis-2018-213271

Takeuchi T,

Genovese MC,

Haraoui B,

Li Z,

Xie L,

Klar R,

Pinto Correia A,

Otawa S,

Lopez-Romero P,

de la Torre I,

Rooney TP,

Smolen JS

In active RA patients, with an inadequate response (IR) to DMARDs who achieve low disease activity (LDA) following baricitinib (BARI) 4 mg treatment, disease control is better maintained with continued BARI 4 mg compared to tapering to 2 mg.The objective of this study was to investigate the effect of BARI tapering in patients achieving sustained disease control with BARI 4 mg.In the long-term extension study RA-BEYOND, patients receiving BARI 4 mg who achieved sustained LDA or remission at two c...

Keywords:

• JAK,
• Baricitinib

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

JAK阻害薬治療中関節リウマチ患者の有害事象，臨床的配慮 およびマネージメント

Exp Rev Clin Immunol 2018 Nov;14(11):945-956. DOI: 10.1080/1744666X.2018.1504678

Atzeni F,

Talotta R,

Nucera V,

Marino F,

Gerratana E,

Sangari D,

Masala IF,

Sarzi-Puttini P

Janus kinase (JAK) inhibitors are efficacious in patients with moderate-to-severe RA and have a favourable safety profile. However adverse events (AE), in particular infections, are associated with the use of JAK inhibitors. This paper reviews the mechanism behind JAK inhibitors, the AEs associated with them, and provides consideration in the management of AEs in clinical practice. Data on two RA approved JAK inhibitors – tofacitinib (TOF) and baricitinib (BARI) – was obtained using PubMed, Medl...

Keywords:

• JAK,
• Safety,
• Review

従来型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ウパダシチニブの安全性と有効性 (SELECT-NEXT): 無作為化二重盲検プラセボ対照フェーズ3治験

Lancet 2018;391:2503–12

Burmester GR,

Kremer JM,

Van den Bosch F,

Kivitz A,

Bessette L,

Li Y,

Zhou Y,

Othman AA,

Pangan AL,

Camp HS

Patients with moderate-to-severe active RA had significant improvements in clinical signs and symptoms with upadacitinib (UPA) compared with placebo.In Phase 2 studies, UPA showed favourable efficacy when administered twice daily as an immediate-release formulation at doses of 6–12 mg in patients with active RA who had TNFi-IR.1,2 An extended-release formulation allowing once-daily (QD) administration was developed for Phase 3 studies. SELECT-NEXT was a double-blind, multicentre, Phase 3 study t...

Keywords:

• JAK,
• Upadacitinib,
• Phase 3

患者特徴は関節リウマチにおける生物学的製剤選択に影響し, non-TNFi をTNFiよりも有害に見せてしまう

Ann Rheum Dis 2018; 77:650–57 DOI: 10.1136/annrheumdis-2017-212395

Frisell T,

Baecklund E,

Bengtsson K,

Giuseppe DD,

Forsblad-d’Elia H,

Askling J,

on behalf of the ARTIS Study Group

Analysis of patient characteristics revealed that older and less healthy patients with RA were more likely to receive non-TNFi bDMARDs as a first bDMARD compared to other treatments.This study aimed to describe patient characteristics at initiation of bDMARD treatment at two-time points: first bDMARD initiation and switch to second bDMARD after TNFi treatment. The second aim of the study was to estimate the potential of treatment channelling to confound results in comparative treatment studies i...

Keywords:

• Safety,
• Review