September 2024

Glucocorticoid sparing effect of Janus Kinase inhibitors compared to biological Disease Modifying Anti-Rheumatic Drugs in rheumatoid arthritis: A single-centre retrospective analysis

Journal Reference: Rheum. 2024 Epub ahead of print doi: 10.1093/rheumatology/keae455.

Adami et al. conducted a retrospective analysis to evaluate the GC sparing effects of JAKi versus bDMARDs in rheumatoid arthritis patients. They found that JAKi therapy was associated with a significant reduction in GC dose compared with bDMARDs. This suggests that JAKi could be more effective in reducing long-term GC exposure in RA patients.

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June 2024

A disease-associated gene desert directs macrophage inflammation through ETS2

Nature 2024 doi: 10.1038/s41586-024-07501-1 Epub ahead of print

Stankey, et al. used functional genomics to show that the ETS2 gene is a central regulator of human inflammatory macrophages. They also found that ETS2 was disrupted by JAK inhibitors and MEK inhibitors, with multiple MEK inhibitors being shown to downregulate ETS2-target genes.

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February 2024

Effectiveness and Safety of Filgotinib in Rheumatoid Arthritis: A Real-life Multicentre Experience

Clin Exp Rheumatol 2024 doi 10.55563/clinexprheumatol/k78ug3 Epub ahead of print

This real-world observational study by La Barbera, et al. confirms that filgotinib is efficacious and safe for use in the management of RA. The authors also report that improvements in clinical and laboratory features were greater in bDMARD-naïve patients with RA.

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September 2023

Efficacy and Safety of the TYK2/JAK1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial

Arthritis Rheumatol. 2023;75(8):1370–1380 doi: 10.1002/art.42519

Phase IIb study of brepocitinib in patients with PsA concludes that treatment with brepocitinib 30 mg and 60 mg QD, was superior to placebo at reducing signs and symptoms of PsA and was well-tolerated over 52 weeks.

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October 2020

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 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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February 2018

Tofacitinib with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Chinese Patients with Rheumatoid Arthritis: Patient-reported Outcomes from a Phase 3 Randomised Controlled Trial

Int J Rheum Dis 2018; 21(2):402–14

This Chinese sub-population of patients with RA from ORAL Sync reported significant improvements in patient-reported outcomes (PROs), which were maintained up to 12 months from tofacitinib (TOF) treatment initiation. ORAL Sync was a randomised, Phase 3 study investigating TOF therapy in combination with csDMARDs in patients with active RA who had previously had an inadequate response to csDMARDs. To date, this is the only Phase 3 study of TOF in patients from China with RA. This analysis include...

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July 2017

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

Ann Rheum Dis 2017;76:1253-1262. DOI 10.1136/annrheumdis-2016-210457

This analysis of exposure to tofacitinib, an oral JAKi for the treatment of RA, for up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. Adverse events were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.Data were collated into an integrated safety summary of tofacitinib in adult patients with active RA, and included data spanning the tofacitinib clinical programme: from 2 Pha...

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September 2016

Treating Experimental Arthritis with the Innate Immune Inhibitor Interleukin-37 Reduces Joint and Systemic Inflammation

Rheumatology (Oxford) 2016; DOI 10.1093/rheumatology/kew325

IL-37, a member of the IL-1 family, has recently been characterised as a fundamental inhibitor of innate inflammation. This study examines the effects of recombinant IL-37 on joint inflammation and pathology in a mouse model of arthritis, and also explores its potential in the treatment of human joint inflammation.In this mouse model of experimental arthritis, short-term, low-dose treatment with IL-37 suppressed joint and systemic inflammation. Wild-type mice received three intraperitoneal doses...

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February 2014

Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets

Rheumatology doi:10.1093/rheumatology/ket414

Despite biologic therapies greatly improving the treatment of rheumatoid arthritis, many patients do not respond to current treatments or do not maintain response to these treatments. This review covers the evidence for the newly discovered role of Th17 cells, IL-12 and IL-17 family of cytokines in the pathogenesis of RA as well as the development of new therapies targeting these cytokines. With current biologics targeting cytokines such as TNF, IL-1ß and IL-6, the discovery of the Th17 subset o...

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October 2013

A meta-analysis of p38 mitogen-activated protein kinase inhibitors in patients with active rheumatoid arthritis

Clinical Rheumatology 2013 doi 10.1007/s10067-013-2340-1

The role of p38-MAPK inhibitors in treating RA is the subject of some debate. Li et al. therefore performed the first meta-analysis of the current data to evaluate the efficacy and safety of these compounds. The authors identified 3 papers, covering 4 RCTs, for analysis and the results showed that p38-MAPK inhibition achieves a better level of ACR20 improvement vs. placebo, but showed no meaningful difference in ACR50, DAS28 or CRP levels past week 12. Due to the inadequate number and quality of...

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