Publications

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

メトトレキサート未治療の中等度から重度の活動性関節リウマチ患者に おけるウパダシチニブの有効性と安全性 (SELECT-EARLY): 無作為化, 二 重盲検, 実薬対照, 多施設多国試験

Arthritis Rheumatol 2020

van Vollenhoven R,

Takeuchi T,

Pangan AL,

Friedman A,

Mohamed MEF,

Chen S,

Rischmueller M,

Blanco R,

Xavier RM,

Strand V

Upadacitinib monotherapy demonstrated superior clinical, radiographic, and patient-reported outcomes versus methotrexate in methotrexate-naïve RA patients.This 48-week double-blind active comparator study investigated upadacitinib monotherapy in patients with early RA, who were either methotrexate-naïve, or who had very limited exposure. 947 patients were randomised to once-daily upadacitinib 15 or 30 mg, or weekly methotrexate. Unusually, there were two separate primary endpoints, selected for ...

Keywords:

• JAK,
• Upadacitinib,
• Phase 3

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

COVID-19 から関節炎の炎症経路を再考

Nat Rev Rheumatol 2020 doi.org/10.1038/s41584-020-0451-z

Schett G,

Manger B,

Simon D,

Caporali R

This review investigates the potential implications of COVID-19 on the field of rheumatology. Common pathways in COVID-19 and RA have provided rationale for the trial of DMARD therapies in treatment of severe COVID-19 infections. Safety considerations of RA patients undergoing immunomodulatory treatments are reviewed. Recommendations suggest that RA patients should continue DMARD treatment, whereas glucocorticoid use could be deleterious in COVID-19 infection and should be considered carefully, ...

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

トファシチニブによるヤヌスキナーゼ阻害の骨修復過程への影響

Int J Mol Sci 2020;21:865

Gaber T,

Brinkman ACK,

Pienczikowski J,

Diesing K,

Damerau A,

Pfeiffenberger M,

Lang A,

Ohrndorf S,

Burmester G-R,

Buttgereit F,

Hoff P

TOF demonstrated a dose-dependent promotion of human mesenchymal stromal cell (hMSC) recruitment under hypoxia, while inhibiting recruitment under normoxia. TOF also dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity. As people age, they are more likely to suffer from fractures and delayed bone healing, as well as degenerative joint diseases or osteoporosis. Bone metabolism and fracture healing may be negatively affected by underlyin...

Keywords:

• JAK,
• Tofacitinib,
• Bone

JAK 阻害は安定状態で骨量を増加し、破骨細胞刺激による病的骨量減少を改善

Sci Transl Med 2020;12(530):pii: eaay4447

Adam S,

Simon N,

Steffen U,

Andes FT,

Scholtysek C,

Müller DIH,

Weidner D,

Andreev D,

Kleyer A,

Culemann S,

Hahn M,

Schett G,

Krönke G,

Frey S,

Hueber AJ

JAKi significantly increased osteoblast function but showed no direct effects on osteoclasts.JAK signalling has emerged as an important therapeutic target for inflammatory disease, and the immunomodulation of JAK inhibition is well defined. Less well understood is the influence of this new class of drugs on bone homeostasis. This is important, as cytokine dysregulation triggers bone loss, and periarticular erosions contribute to the pathogenesis of RA. This study investigated the effect of BARI ...

Keywords:

• JAK,
• Bone

RA診療におけるEULAR推奨– 2019 アップデートとJAK阻害薬に関する共同声明

Ann Rheum Dis. 2020 Jan 22. pii: annrheumdis-2019-216655.

Smolen JS,

Landewé RBM,

Bijlsma JWJ,

Burmester GR,

Dougados M,

Kerschbaumer A,

McInnes IB,

Sepriano A,

et al.

The EULAR recommendations for the management of RA have become increasingly useful in providing rheumatologists, patients, payers and other stakeholders with the evidence-based guidance and views of experts on the optimal use and sequence of pharmaceutical therapies in patients with RA. Over the course of the last decade, the evolution of the treatment landscape has already required two updates. The release of the new addition updates the 2016 recommendations.An international task force consider...

Keywords:

• EULAR

Highlights of 2019

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

McInnes. I

2019 was another remarkable year in cytokine signalling. We can be optimistic that clinical practice for inflammatory arthritis will continue to improve, with promising long-term safety data supporting the use of established JAK inhibitors; tofacitinib and baricitinib, in addition to exciting phase III clinical data for filgotinib and newly approved upadacitinib. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respecti...

Keywords:

• Review