April 2020

Relative Efficacy and Safety of Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib in Comparison to Adalimumab in Patients with Active Rheumatoid Arthritis

Z Rheumatol. 2020 DOI: 10.1007/s00393-020-00750-1

This Bayesian network meta-analysis, comparing the relative efficacy and safety of JAK inhibitors, determined BARI 4mg + MTX and UPA 15mg + MTX were the most effective. The analysis included 5451 patients with an inadequate response to MTX and active RA, from four RCTs. Relative effects were converted into a probability allowing each treatment to be ranked. BARI and UPA had significantly higher ACR20 response rates than ADA 40mg + MTX whilst TOF 5mg and FIL 200mg had comparable ACR20 response ra...

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Long-term Effectiveness of Live Herpes Zoster Vaccine in Patients with Rheumatoid Arthritis Subsequently Treated with Tofacitinib

Ann Rheum Dis. 2020 10.1136/annrheumdis-2019-216566

The results of ORAL Sequel suggest that the live zoster vaccine (LZV) may not provide adequate long-term protection in patients with RA receiving TOF. This LTE study enrolled 100 patients with RA, 14 weeks post LZV vaccination. Patients received either TOF 5 mg BID, or TOF 10 mg BID in addition to any background csDMARDs. Incidence rates and 95% CIs for HZ post-vaccination were calculated based on time to first event. Short-term varicella zoster vaccine (VZV) specific immunity was evaluated at ...

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IgA Vasculitis Developed as an Adverse Effect of Tofacitinib Taken for Rheumatoid Arthritis

Intern Med. 2020;59(6):817-821

Nephrotoxicity is a key side effect of NSAIDs and DMARDs used to treat RA, while biologics can reportedly cause proliferative glomerulonephritis or crescentic glomerulonephritis. This report reviews a patient on TOF presenting IgA vasculitis as an adverse effect that fully resolved following termination of TOF.Drug induced IgA vasculitis has been previously described for anti-TNFɑ therapies, but this is the first report with JAK inhibitor therapy. This is a case report of a 67-year old woman wit...

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March 2020

Impact of Janus Kinase Inhibition with Tofacitinib on Fundamental Processes of Bone Healing

Int J Mol Sci 2020;21:865

TOF demonstrated a dose-dependent promotion of human mesenchymal stromal cell (hMSC) recruitment under hypoxia, while inhibiting recruitment under normoxia. TOF also dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity. As people age, they are more likely to suffer from fractures and delayed bone healing, as well as degenerative joint diseases or osteoporosis. Bone metabolism and fracture healing may be negatively affected by underlyin...

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February 2020

Osteoimmunology In Rheumatoid and Psoriatic Arthritis: Potential Effects of Tofacitinib on Bone Involvement

Clin Rheumatol. 2020

Data showing that TOF can inhibit unbalanced osteoclastogenesis in RA suggests that targeting the JAK-STAT pathway can halt bone erosion, as TOF has been shown to reduce articular bone erosion in RA and PsA.The authors in this review summarise current knowledge on the relationship between the immune system and the skeleton before examining the involvement of JAK-STAT signalling in bone homeostasis while discussing the evidence on the benefit of TOF on prevention of bone involvement in RA and PsA...

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Preferential Inhibition of JAK1 Relative to JAK3 by Upadacitinib: Exposure-Response Analyses of Ex Vivo Data From 2 Phase 1 Clinical Trials and Comparison to Tofacitinib

Pharmacodynamics. 2020

Ex vivo pharmacodynamic assay results demonstrated a greater selectivity of UPA on JAK1 versus JAK3 compared to TOF. This analysis conducted ex vivo stimulation of STAT3 phosphorylation by IL-6 as a measure of JAK1 activity and STAT5 phosphorylation by IL-7 as a measure of JAK1/JAK3 activity. Change in pSTAT3 and pSTAT5 were calculated at 1, 6 and 12 hours following drug administration using samples collected from healthy subjects and subjects with RA, from 2 phase 1 studies. Exposure-response m...

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January 2020

Tofacitinib in Combination with Methotrexate in Patients with Rheumatoid Arthritis: Patient-reported Outcomes from the 24-month Phase 3 ORAL Scan study

Clin Exp Rheumatol . Sep-Oct 2020;38(5):848-857. Epub 2019 Dec 19.

In the ORAL SCAN study, patients receiving TOF 5 mg or 10 mg BID reported significant improvements in patient-reported outcomes at month 3 compared with placebo, which were maintained through 24 months of treatment.RA causes a significant health and socioeconomic burden and affects all aspects of health related quality of life. ORAL Scan included patients with active RA and inadequate response to MTX who were randomised to receive TOF 5 mg or 10 mg BID plus MTX or PBO. This study evaluated the i...

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December 2019

Highlights of 2019

Please click the links below to go to the CSF review of each paper

2019 was another remarkable year in cytokine signalling. We can be optimistic that clinical practice for inflammatory arthritis will continue to improve, with promising long-term safety data supporting the use of established JAK inhibitors; tofacitinib and baricitinib, in addition to exciting phase III clinical data for filgotinib and newly approved upadacitinib. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respecti...

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November 2019

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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October 2019

Risk Factors for Major Adverse Cardiovascular Events in Phase III and Long-Term Extension Studies of Tofacitinib in Patients with Rheumatoid Arthritis

Arthritis Rheumatol .2019 Sep;71(9):1450-1459. doi: 10.1002/art.40911. Epub 2019 Aug 6.

Post hoc analyses of the six ORAL studies and two LTE’s suggested that after 24 weeks of TOF treatment, increases in HDL-c and decreases in the TC/HDL-c ratio appeared to be associated with reduced future MACE risk in RA patients. 52 MACE occurred in 4076 patients over 12873 patient-years of exposure. Separate Cox regression models were used to evaluate traditional CV risk factors’ association with time to first MACE at baseline and changes in lipid levels with time to future MACE after 24 weeks...

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