Publications

乾癬性関節炎患者におけるトファシチニブ: ２つのフェーズ3臨床試験での皮膚症状, 徴候と健康関連QOL

J Eur Acad Dermatol Venereol 2020;34:2809–2820.

Merola JF,

Papp KA,

Nash P,

Gratacós J,

Boehncke W-H,

Thaçi D,

Graham D,

Hsu M-A,

Wang C,

Wu J,

Young P

Considering the multi-domain nature of PsA, effective treatments must demonstrate efficacy across a range of clinical and patient-reported outcomes. Dermatologic symptoms often precede rheumatic manifestations in people with PsA, typically by 10 years. Tofacitinib demonstrated significant improvements across a range of outcomes including burdensome dermatologic symptoms. This post hoc analysis included data from two double-blind, Phase 3 studies in patients with active PsA and an inadequate resp...

Keywords:

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

Highlights of 2020

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

McInnes. I

2020 unfolded apace, dominated by COVID-19 - we have all had to adapt in our practice and in our knowledge base. Amid this there have continued to be a constant flow of publications and science in cytokine signaling, and as in previous years as we come the end of 2020, I will highlight some of the notable papers of the year. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respective detailed summaries below:

Keywords:

• Review

関節リウマチの臨床試験とアメリカのCorrona RAレジストリにおけるTofacitinibと生物学的DMARDsの年齢別 (<65 vs ≥65 歳)の 感染症と重篤感染症発生率

Ann Rheum Dis 2020; DOI: 10.1136/annrheumdis-2020-218992

Winthrop KL,

Citera G,

Gold D,

Henrohn D,

Connell CA,

Shapiro AB,

Shi H,

Onofrei AM,

Pappas DA,

Schulze-Koops H

Reports from clinical trials and the US Corrona RA registry showed that serious infection event (SIE) incidence was higher in older versus younger patients with RA receiving 10 mg BID of TOF and ADA, however, SIE risk was similar between age groups with TOF 5 mg BID and ADA.Data were collected from Phase II–IV tofacitinib studies, and the US Corrona RA registry. The clinical data set evaluated patients receiving TOF 5 and 10 mg BID versus TNFi (ADA/ETN) in RA patients aged ≥50 years. The EMA rec...

Keywords:

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

関節リウマチ治療における baricitinib の有効性 : 実臨床にお ける線維化およびバイオマーカーに対する修飾効果

Int. J. Mol. Sci. 2020; 21:6632 DOI: 10.3390/ijms21186632

Amrhein J,

Drynda S,

Schlatt L,

Karst U,

Lohmann C,

Ciarimboli G,

Bertrand J

Amrhein et al examined the different uptake and expulsion mechanisms of BARI and TOF in cellular assays. Different cellular uptake mechanism for BARI and TOF was observed and showed that BARI’s transport was not dependent on organic cation transporters. Results indicated TOF was exported from RASF in a MATE-1 dependent way. TOF might be exported from healthy cells, thereby not inhibiting JAK pathway in these cellsThe interaction of BARI and TOF with OCTs was investigated using quenching experime...

Keywords:

• JAK,
• Tofacitinib,
• Baricitinib,
• MOA

関節リウマチ、乾癬、乾癬性関節を対象としたトファシチニブ開発 プログラムと実臨床データにおける静脈および動脈血栓塞栓症 発生率

Annals of the Rheumatic Diseases 05 August 2020 2020 Nov;79(11):1400-1413. doi: 10.1136/annrheumdis-2019-216761. Epub 2020 Aug 5.

Mease P,

Charles-Schoeman C,

Cohen S,

Fallon L,

Woolcott J,

Yun H,

Kremer J,

Greenberg J,

Malley W,

Onofrei A,

Kanik KS,

Graham D,

Wang C,

Connell C,

Valdez H,

Hauben M,

Hung E,

Madsen A,

Jones TV,

Curtis JR

Concerns surrounding increased rates of PE and cardiovascular associated deaths has led to black box warnings when prescribing JAK inhibitors. As such, ongoing investigations regarding cardiovascular and VTE event risks in JAK inhibitor therapies, both clinical and real-world, are vital. Mease and colleagues consider data from clinical tofacitinib development programmes, and the ongoing real-data study A3921133. Conclusions from data analysis state that those with pre-existing cardiovascular and...

Keywords:

• JAK,
• Tofacitinib,
• Safety

トファシチニブで治療された関節リウマチ患者における 間質性肺炎の頻度

Journal of Clinical Rheumatology, Aug 2020 doi: 10.1097/RHU.0000000000001552.

Citera G,

Mysler E,

Madariaga H,

Cardiel M H,

Castaneda O,

Fischer A,

Richette P,

Chartrand S,

Park J K,

Strengholt S,

Rivas J L,

Thorat A V,

Girard T,

Kwok K,

Wang L

This study highlights the importance of accounting for known risk factors of RA-ILD in clinical practice. Interstitial lung disease (ILD) is an extra-articular manifestation of RA. The post-hoc investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD. This post-hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 21 Phase 1-4, and 2 long-term ex...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Lung / ILD

合成および生物学的DMARDs: 関節リウマチ診療に対する EULAR リコメンデーションに情報提供したシステマティック 文献レビュー

Annals of the Rheumatic Diseases 2020;79:760-770

Sepriano A,

Kerschbaumer A,

Smolen JS,

Van Der Heijde D,

Dougados M,

Van Vollenhoven R,

McInnes IB,

Bijlsma JW,

Burmester GR,

De Wit M,

Falzon L,

Landewé R

This SLR informed the 2019 EULAR taskforce updating recommendations for RA management. Overall, no new safety signals were reported. The known safety profile of bDMARDs was confirmed and extended to tsDMARDS. IL-6i associated lower intestinal perforation has been further confirmed, while VTE and PE concerns in JAKi treatment need further evaluation.Previous updates for the EULAR recommendations on RA pharmacological management were conducted in 2016. In this SLR safety of csDMARDs, tsDMARDs, and...

Keywords:

• Safety,
• EULAR

乾癬性関節炎に対する薬物治療: 乾癬性関節炎診療に対するEULAR リコメンデーション改訂の ためのシステマティック文献レビュー

Annals of the Rheumatic Diseases 2020;79:778-786

Kerschbaumer A,

Smolen JS,

Dougados M,

De Wit M,

Primdahl J,

McInnes I,

Van Der Heijde D,

Baraliakos X,

Falzon L,

Gossec L

This SLR reviewed data on pharmacological treatment of PsA. Findings informed the 2019 EULAR taskforce when updating recommendations for PsA management. Overall, no new safety signals were reported. Encouragingly, LTEs of JAKi did not report any venous thromboembolic events or PEs. Efficacy was demonstrated for a range of bDMARD and tsDMARD therapies in various disease domains. Efficacy varied between PsA manifestations and between therapies. Observational data demonstrated efficacy when switchi...

Keywords:

• EULAR

活動性乾癬性関節炎に対するTofacitinibの安全性と有効性: オープンラベル長期延長試験であるOPAL Balanceの中間解析

Rheumatol Ther 2020 doi.org/10.1007/s40744-020-00209-4

Nash P,

Coates LC,

Kivitz AJ,

Mease PJ,

Gladman DD,

Covarrubias-Cobos JA,

FitzGerald O,

Fleishaker D,

Wang C,

Wu J,

Hsu M,

Menon S,

Fallon L,

Romero AB,

Kanik KS

This 3-year, open-label, LTE study follows PsA patients previously treated in pivotal studies OPAL Broaden and OPAL Beyond. It demonstrates maintained safety and efficacy of tofacitinib up to 36 and 30 months, respectively. No new safety concerns are highlighted. Previous P3 studies, OPAL Broaden and OPAL Beyond, demonstrated safety and efficacy of 5mg and 10mg tofacitinib BID in PsA. These patients rolled over to OPAL Balance for a period of 36 months. 686 participants were used in this interim...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Efficacy,
• LTE

バイオナイーブ関節リウマチ患者とバイオスイッチ患者におけ る7 生物製剤とtofacitinibの継続率: ANSWER コホート試験

Arthritis Res Ther 2020;22:142

Ebina K,

Hirano T,

Maeda Y,

Yamamoto W,

Hashimoto M,

Murata K,

Takeuchi T,

Shiba H,

Son Y,

Amuro H,

Onishi A,

Akashi K,

Hara R,

Katayama M,

Yamamoto K,

Kumanogoh A,

Hirao M

This paper is based upon a long-term cohort study, namely the ANSWER cohort, an observational multi-centre registry of RA patients in the Kansai district of Japan. Analyses demonstrate a difference in observed drug retention between bDMARDs-naïve and bDMARDs-switched patients. 7 bDMARD treatments were compared in patients with no prior exposure to biologics, with abatacept showing the greatest retention rate. In patients that had switched between these same bDMARDs or to tofacitinib throughout t...

Keywords:

• JAK,
• TNF,
• Tofacitinib,
• Real-World