Publications

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

中等症から重症の関節リウマチ患者におけるbaricitinibの3年治療: 長期試験結果

Rheumatology 2020; doi:10.1093/rheumatology/keaa576

Smolen JS,

Xie L,

Jia B,

Taylor PC,

Burmester G,

Tanaka Y,

Elias A,

Cardoso A,

Ortmann R,

Walls C,

Dougados M

Three year follow up data for baricitinib demonstrated efficacy in populations that span the clinical disease continuum in RA, including DMARD-naïve, MTX-IR, csDMARD-IR, and bDMARD-IR and was well tolerated. This study evaluated achievement and maintenance of LDA, remission and physical functioning in patients treated with baricitinib for up to 3 years. Data were analysed from two 52-week, Phase 3 studies (RA-BEAM and RA-BEGIN), and one ongoing long-term extension (RA-BEYOND). Patients completin...

Keywords:

• JAK,
• Baricitinib,
• LTE,
• Efficacy

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.

Alessandro M,

Perillo F,

Refini R,

Bergantini L,

Bellisai F,

Selvi E,

Cameli P,

Manganelli S,

Conticini E,

Cantarini L,

Sestini P,

Frediani B,

Bargagli E

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...

Keywords:

• JAK,
• Baricitinib,
• Basic Science,
• Biomarkers

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.

Zhang X,

Zhang Y,

Qiao W,

Zhang J,

Qi Z

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...

Keywords:

• JAK,
• Baricitinib

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

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

López-Romero P,

Martinez-Gamboa L,

Bang H,

de la Torre I,

Holzkämper T,

Feist E

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...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Bone,
• Radiographic

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

Winthrop KL,

Harigai M,

Genovese MC,

Lindsey S,

Takeuchi T,

Fleischmann R,

Bradley JD,

Byers NL,

Hyslop DL,

Issa M,

Nishikawa A,

Rooney TP,

Witt S,

Dickson CL,

Smolen JS,

Dougados M

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...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Infections

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

Fleischmann R,

Takeuchi T,

Schiff M,

Schlichting D,

Xie L,

Issa M,

Stoykov I,

Lisse J,

Martinez-Osuna P,

Rooney T,

Zerbini CAF

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...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Safety,
• Switching

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

バリシチニブの一時中断: 関節リウマチ患者における中断 の特徴と臨床アウトカムへの影響

Arth Res Ther 2020;22:115 doi.org/10.1186/s13075-020-02199-8

Emery P,

Tanaka Y,

Cardillo T,

Schlichting D,

Rooney T,

Beattie S,

Helt C,

Smolen JS

This study aimed to characterize temporary interruptions of baricitinib and describe their impact on efficacy and safety. Brief interruptions during phase 3 baricitinib trials were associated with minor increases in symptoms which were resolved following treatment. In life-long, chronic conditions such as RA, interruption of therapy is common for various reasons, such as side effects, non-compliance, or because a patient requires surgery. Concerns have been raised that these treatment breaks cou...

Keywords:

• JAK,
• Baricitinib,
• Efficacy