Publications

Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis

Ann Rheum Dis. 2022. Epub ahead of print doi: 10.1136/annrheumdis-2021-221323

Lopez-Romero P,

de la Torre I,

Haladyj E,

Aletaha D,

Smolen JS

Baricitinib reduces structural damage progression versus placebo with background MTX and/or MTX, even in patients with moderate or high disease activity.In patients with RA, TNFi, IL-6i and rituximab have been shown to uncouple the link between disease activity and radiographic progression such that patients are protected from structural damage progression even if remission/low disease activity is not achieved.As such, Lopez-Romero, et al. aimed to evaluate if baricitinib further enhances diseas...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Radiographic

Comparison of the effects of baricitinib and tocilizumab on disease activity in patients with rheumatoid arthritis: a propensity score matching analysis

Clin Rheumatol. 2021 Jun 16. DOI: 10.1007/s10067-021-05815-3

Asai S,

Takahashi N,

Kobayakawa T,

Kaneko A,

Watanabe T,

Kato T,

Nishiume T,

Ishikawa H,

Yoshioka Y,

Kanayama Y,

Watanabe T,

Hirano Y,

Hanabayashi M,

Yabe Y,

Yokota Y,

Suzuki M,

Terabe K,

Ishiguro N,

Imagama S,

Kojima T.

The influence of inflammation on patient global assessment (PGA) improvements differs between baricitinib and tocilizumab differs. Adequate PGA improvement remains one of the unmet needs in current RA treatment.Asai, et al. compared the effects of baricitinib and tocilizumab on disease activity in patients with RA while investigating the influence of inflammation on PGA improvement.Using data from a multicentre registry, 48 propensity-matched pairs of patients, who had been observed for longer t...

Keywords:

• JAK,
• IL-6,
• Baricitinib,
• Tocilizumab,
• Efficacy

Tofacitinib versus tocilizumab in the treatment of biological-naïve or previous biological-failure patients with methotrexate-refractory active rheumatoid arthritis

RMD Open. 2021;7(2):e001601.

Mori S,

Urata Y,

Yoshitama T,

Ueki Y.

Findings from a multicentre cohort study in Japan provide important information that is expected to aid in determining the position of tofacitinib in the treatment algorithm for RA.Mori S, et al. compared therapeutic outcomes, from real-world registries, at 12 months between tofacitinib-treated and tocilizumab-treated patients to clarify whether tofacitinib should only be considered as an option for patients who have either failed to respond to at least one bDMARD or are MTX-resistant/-intoleran...

Keywords:

• JAK,
• IL-6,
• Tofacitinib,
• Tocilizumab,
• Efficacy,
• Safety

Diminished cytokine-induced Jak/STAT signaling is associated with rheumatoid arthritis and disease activity

PLoS ONE 2021;16(1):e0244187

Ptacek J,

Hawtin RE,

Sun D,

Louie B,

Evensen E,

Mittleman BB,

Cesano A,

Cavet G,

Bingham CO III,

Cofield SS,

Curtis JR,

Danila MI,

Raman C,

Furie RA,

Genovese MC,

et al

This analysis provides evidence that immune cell signalling pathways are important in RA. There were consistent differences between RA patients and healthy controls in IFNα, IL-6, IL-10 and GM-CSF+ IL-2 induced JAK/STAT signalling in multiple immune cell subsets.We know that RA is characterised by dysregulation of immune responses, but the exact cause is unknown. Recently, single-cell transcriptomics and mass cytometry confirmed the critical role of activated immune cells and fibroblasts, increa...

Keywords:

• JAK,
• Basic Science

Preclinical characterisation of itacitinib, a Novel Selective Inhibitor of JAK1, for the Treatment of Inflammatory Diseases

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

Covington M,

He X,

Scuron M,

Li J,

Collins R,

Juvekar A,

Shin N,

Favata M,

Gallagher K,

Sarah S,

Xue CB,

Peel M,

Burke K,

Oliver J,

Fay B,

Yao W,

Huang T,

Scherle P,

Diamond S,

Newton R,

Zhang Y,

Smith

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...

Keywords:

• JAK,
• Itacitinib

Efficacy of Baricitinib in Treating Rheumatoid Arthritis: Modulatory Effects on Fibrotic and Inflammatory Biomarkers in a Real-Life Setting

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

Tofacitinib and Baricitinib Are Taken up by Different Uptake Mechanisms Determining the Efficacy of Both Drugs in RA

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

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

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

COVID-19 revisiting inflammatory pathways of arthritis

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, ...

Filgotinib, a JAK1 Inhibitor, Modulates Disease Related Biomarkers in Rheumatoid Arthritis: Results from Two Randomized, Controlled Phase 2b Trials

Rheumatol Ther. 2020 DOI: 10.1007/s40744-019-00192-5

Tarrant JM,

Galien R,

Wanying L,

Goyal L,

Pan Y,

Hawtin R,

Zhang W,

Van der Aa A and Taylor PC

In this study examining the effect of FIL on a panel of biomarkers, FIL down-modulated several key inflammatory mediators of signalling pathways in RA - independent of MTX background therapy. This confirmed the strong network effects of the JAK1 node in autoimmunity, matrix and cartilage degradation, angiogenesis, and leukocyte adhesion and recruitment. Biomarkers key to RA pathophysiology were measured at baseline, Wk4 and Wk12 in FIL 100 mg, FIL 200 mg or PBO treatment groups from two phase 2b...

Keywords:

• JAK,
• Filgotinib,
• Phase 2,
• MOA,
• Biomarkers