December 2020

免疫介在性炎症性疾患におけるヤヌスキナーゼ阻害薬使用時に考慮すべき点: システマテイックレビュー

RMD Open 2020;6:e001374 doi:10.1136/rmdopen-2020-001374

Trials of JAKi have been conducted in many therapy areas, including rheumatology, dermatology and gastroenterology. In 2019, a task force was set up to create a consensus to guide clinicians on how to use JAKi in clinical practice. This systematic literature review conducted in 2019 support this consensusIn line with EULAR’s standardised operating procedures for recommendations, a literature search was conducted in EMBASE, Medline and the Cochrane Library databases. To evaluate the efficacy of t...

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October 2020

新規選択的 JAK1 阻害薬 Itacitinib INCB039110 の炎症性疾 患治療薬としての前臨床特徴

European Journal of Pharmacology. 2020 Oct 15;885:173505. doi: 10.1016/j.ejphar.2020.173505

Itacitinib is an orally active JAK inhibitor and effectively delayed disease onset, reduced symptom severity, and accelerated recovery of inflammatory diseases in mouse models. Covington M et al demonstrated itacitinib’s high selectivity for JAK 1, its inhibition on IL-2 induced T cell proliferation and JAK/STAT signalling, its ability to also inhibit of the JAK/STAT pathway in response to IL-6 stimulation, and its effect on rat adjuvant induced arthritis model. The study used recombinant enzym...

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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 Immunopharmacol. 2020 Sep;86:106748.

BARI demonstrated to be a safe immune modulator that reduces the concentrations biomarkers of lung fibrosis and inflammation in RA patients, including a subgroup with interstitial lung involvement. Professor Alessandro and colleagues analysed the effects of baricitinib in a population of RA and RA-ILD patients in a real-life setting, describing any changes in lung function parameters, serum inflammatory biomarkers and fibrotic biomarkers after 6 months of treatment. Fifteen patients were recruit...

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BaricitinibはSARS-CoV-2の細胞侵入を阻害しCOVID-19によるサイトカインをコントロールする可能性

Journal of International Immunopharmacology. 2020 Sep;86:106749. doi: 10.1016/j.intimp.2020.106749.

BARI may potentially interrupt the passage of SARS-CoV-2 into the target cells by binding to AAK1 and GAK, which are regulators of the ACE2 receptor regulator identified for its uptake, and could also treat cytokine storm through suppression JAK1/JAK2. Professor Zhang and et al reviewed BARI, as a potential drug to prevent SARS-COV-2 from entering target cells. They also evaluated BARI’s ability to control COVID-19 induced cytokine storm. As a cell surface protein, ACE2 is involved in receptor-m...

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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 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...

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September 2020

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.

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...

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ベースライン 抗CarbV抗体 と 抗MCV 抗体とメトトレキサートまた はバリシチニブで治療されたRA患者における治療反応性と画像 的進行の関連性: RA-BEGINのpost-hoc 解析

Arthritis Res Ther. 2020;22(1):193

Autoantibodies associated with the onset of RA have gained attention in recent years as prognostic biomarkers. Though not used diagnostically, anti-CarbV (carbamylated vimentin) and anti-MCV (vimentin modified by citrullination) baseline titers are being investigated as predictors of treatment response. In this post-hoc analysis of data from the RA-BEGIN cohort of active RA patients, López-Romero and colleagues consider the potential predictive values of baseline anti-CarbV and anti-MCV titers r...

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活動性関節リウマチ患者のBaricitinib の臨床試験 における感染症

Annals of the Rheumatic Diseases, May 2020

Baricitinib, an oral selective JAK1 and JAK2 inhibitor,8 demonstrated significant clinical efficacy in phase 3 RA trials. Pooled data from these trials, including a long-term extension (LTE), inform the safety profile for baricitinib, mainly to evaluate the incidence of infection in patients with active rheumatoid arthritis (RA), with a focus on serious infection, tuberculosis (TB), herpes zoster (HZ) and opportunistic infection (OI). The data collected were from eight double-blind randomised tr...

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August 2020

関節リウマチ治療におけるメトトレキサート併用または非併用でのバリ シチニブの長期有効性と安全性: バリシチニブ単剤継続または、メトト レキサート単剤またはメトトレキサート併用Eバリシチニブからスイッチ でのバリシチニブ単剤の経験

Arthritis Care Res (Hoboken) 2020;72(8):1112-1121

This 24-week update from the baricitinib RA-BEYOND LTE study follows patients previously treated in the pivotal study RA-BEGIN. It demonstrates the maintained safety and efficacy of baricitinib monotherapy, and the effects of concurrent MTX treatment on response rates and patient reported outcomes. Previous P3 study RA-BEGIN demonstrated the superior efficacy of 4mg baricitinib compared to MTX monotherapy up to 52 weeks, with no major safety events being identified. At the end of the trial, pati...

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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

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 ...

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