July 2020

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

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...

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Pharmacological Treatment of Psoriatic Arthritis: A Systematic Literature Research for the 2019 Update of the EULAR Recommendations for the Management of Psoriatic Arthritis

Annals of the Rheumatic Diseases 2020;79:778-786

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...

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June 2020

Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland

RMD Open 2020;6:e001174 doi:10.1136/rmdopen-2020-001174

This nested cohort study found that, in Switzerland, there was a generally limited overall drug maintenance for b/tsDMARD options in RA. Using data from SCQM-RA – a prospective longitudinal registry, overall maintenance (drug survival) was calculated for TNFi, bDMARD-OMA or JAKi in patients with RA.After adjusting for potential confounding factors, there was a higher hazard of drug discontinuation with TNFi compared with tofacitinib; no significant difference was observed between non-TNF bDMARDs...

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Baricitinib In Patients with Rheumatoid Arthritis With Inadequate Response to Methotrexate: Results From A Phase 3 Study

Clin Exp Rheumatol . Jul-Aug 2020;38(4):732-741. Epub 2020 May 20.

This study conducted mainly in Chinese patients with RA, and an inadequate response to MTX, showed that baricitinib 4mg was associated with significant improvements and consistent with the findings from previous clinical trials.The efficacy and safety of baricitinib have been assessed in several clinical trials, predominantly in Caucasian populations. However, evidence on the efficacy and safety of baricitinib in Chinese patients is limited, with only one of the main clinical trial program studi...

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March 2020

JAK Inhibition Increases Bone Mass in Steady state Conditions and Ameliorates Pathological Bone Loss by Stimulating Osteoblast Function

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

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 ...

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February 2020

EULAR Recommendations for the Management of Rheumatoid Arthritis – 2019 Update and Consensus Statement on JAKinibs

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

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...

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November 2019

Comparative Efficacy and Safety of Peficitinib 25, 50, 100, and 150 mg in Patients with Active Rheumatoid Arthritis: A Bayesian Network Meta‑Analysis of Randomized Controlled Trials

Clin Drug Investig .2020 Jan;40(1):65-72. doi: 10.1007/s40261-019-00863-9.

PEF 50, 100, and 150 mg once daily was effective in treating active RA, without causing a significant risk for AEs.Intracellular pathways, including JAK and Tyk-2, are critical for immune cell activation, pro-inflammatory cytokine production, and cytokine signaling. PEF has been developed for use in RA, but the comparative efficacy and safety of regimens and dosages has not been established. A Bayesian network meta-analysis was conducted to combine direct and indirect evidence to assess the rela...

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A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis

Rheumatology (Oxford) 2019;58(10):1755–66

Absolute serious infection rates were low. However, across the JAKinibs, the incidence of HZ is higher than expected for the population. While the risk was numerically greatest with BARI, indirect comparisons between the drugs did not demonstrate any significant difference in risk. How JAKinibs increase the risk of HZ reactivation is unclear, but how different JAKs interact in the immune response suggest that there may be differences in safety profiles between JAKinib drugs, underpinned by their...

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Tofacitinib Modulates the VZV-specific CD4+ T Cell Immune Response in vitro in Lymphocytes of Patients with Rheumatoid Arthritis

Rheumatology (Oxford) 2019;58(11):2051–60

TOF significantly modulated the Th1 response to Varicella-zoster-virus (VZV). The poor VZV-specific cellular immune responses in patients with RA may be considered in recommendations regarding appropriate vaccination strategies for enhancing the VZV-specific Th1 response.Previous studies have shown that treatment with JAKinibs increases HZ incidence compared with conventional DMARDs. This cross-sectional in vitro study aimed to investigate the effect of TOF on the VZV-specific T cell immune resp...

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September 2019

Comparison of Baricitinib, Upadacitinib, and Tofacitinib Mediated Regulation of Cytokine Signalling in Human Leukocyte Subpopulations

Arthritis Res Ther. 2019 Aug 2;21(1):183

Different JAKinibs modulated distinct cytokine pathways to varying degrees, and no agent potently or continuously inhibited an individual cytokine signalling pathway throughout the dosing interval. This study aimed to compare the in vitro cellular pharmacology of BARI, TOF and UPA across relevant leukocyte subpopulations, coupled with their in vivo PK, to determine their effects on distinct cytokine pathways. Peripheral blood mononuclear cells from healthy donors were incubated with different JA...

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