Publications
View and download slide summaries of the latest original articles focusing on cytokine signalling therapies within rheumatoid arthritis. All materials produced by the CSF team are subsequently reviewed and approved by individual steering committee members.
Identification of novel off targets of baricitinib and tofacitinib by machine learning with a focus on thrombosis and viral infection
Sci Rep. 2022 doi: 10.1038/s41598-022-11879-1
Established machine learning approaches, based on ligand similarity, identified previously unknown off-target interactions of baricitinib and tofacitinib, and adds to the evidence that these JAK inhibitors are promiscuous binders, and highlight the potential for repurposing.
Effect of Tofacitinib on Pain, Fatigue, Health-related Quality of Life and Work Productivity in Patients with Active Ankylosing Spondylitis: Results from A Phase III, Randomised, Double-blind, Placebo-controlled Trial
RMD Open 2022 doi:10.1136/rmdopen-2022-002253
Navarro-Compán et al, determined the effectiveness of tofacitinib in patients with active ankylosing spondylitis in a Phase III, randomised, double-blind, placebo-controlled trial.
The Impact of Tofacitinib on Fatigue, Sleep, and Health‑Related Quality of Life in Patients with Rheumatoid Arthritis: A Post Hoc Analysis of Data from Phase 3 Trials
Arthritis Res Ther. 2022;24(1):83 doi:10.1186/s13075-022-02724-x
This was an exploratory post hoc analysis of pooled data, from over 2000 patients in three Phase 3 studies of tofacitinib, which demonstrates an association between tofacitinib treatment and significantly greater improvements in fatigue, sleep, and health-related quality of life (HRQoL), compared with placebo.
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Effectiveness of baricitinib and tofacitinib compared with bDMARDs in RA: results from a cohort study using nationwide Swedish register data
Rheumatology (Oxford). 2022. Epub ahead of print doi: 10.1093/rheumatology/keac068
Data from the Swedish Rheumatology Quality Register and Swedish Registries, show a higher treatment retention and overall equivalent or better treatment response on baricitinib, compared with bDMARDs or tofacitinib, but no statistically significant differences between tofacitinib and bDMARDs.In this largest population-based study to date, comparing RA patients initiating baricitinib, tofacitinib or bDMARDs, Barbulescu, et al. help to fill some of the current knowledge gaps surrounding the effica...Keywords:
Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label, long-term extension study (ORAL Sequel)
Clin Rheumatol. 2022 Jan 1. Epub ahead of print doi: 10.1007/s10067-021-05908-z
Post-hoc analysis shows that dosing up from tofacitinib 5 to 10 mg BID is associated with improved efficacy for up to 12 months, versus staying on 5 mg BID, and dosing down from 10 to 5 mg BID is not generally associated with a significant loss of efficacy.Although clinical trials have generally shown no significant differences, in terms of efficacy and safety, when switching tofacitinib dose up or down, these per-protocol switches are not directly informative for clinical decision-making in dai...Keywords:
Effect of JAK inhibitors on high- and low-density lipoprotein in patients with rheumatoid arthritis: a systematic review and network meta-analysis
Clin Rheumatol. 2022. Epub ahead of print doi: 10.1007/s10067-021-06003-z
Systematic review and network meta-analysis highlight that RA patients who receive recommended doses of the five approved JAK inhibitors (tofacitinib, baricitinib, upadacitinib, filgotinib, and peficitinib) are likely to experience an increase in serum low- and high-density lipoprotein (LDL and HDL) levels.JAK inhibitors have been associated with alterations in levels of LDL and HDL cholesterol, which may lead to dyslipidaemia (an important risk factor for cardiovascular disease). However, the e...Keywords:
Tofacitinib and risk of cardiovascular outcomes: results from the Safety of Tofacitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study
Ann Rheum Dis. 2022 Jan 13. Epub ahead of print doi: 10.1136/annrheumdis-2021-221915
Real-world evidence finds no increased risk of CV outcomes with tofacitinib, in comparison with TNFi, in patients with RA. However, an elevated risk of CV outcomes cannot be ruled out in patients with CV risk factors or history of CVD.Recent post-marketing findings from the ‘ORAL Surveillance’ trial have raised concerns that tofacitinib, in comparison with TNFi, may increase the risk of CV disease in patients with RA who are at least 50 years of age and with at least one risk factor for CVD. To ...Keywords:
Cardiovascular and Cancer Risk With Tofacitinib in Rheumatoid Arthritis
N Engl J Med 2022;386:316–26. doi: 10.1056/NEJMc2202778
In this paper, Ytterberg et al. compare incidence of MACE and cancers (excluding NMSC) with tofacitinib 5 mg BID, tofacitinib 10 mg BID and TNFi. They found that risk of MACE and cancer were higher with tofacitinib versus TNFi, and did not meet noninferiority criteria.This prospective head-to-head safety trial compared tofacitinib to TNFi, and was required by the FDA after increases in lipid levels and cancers were observed during tofacitinib drug development. ...Keywords:
Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment
Rheumatol Ther. 2021. Epub ahead of print. doi: 10.1007/s40744-021-00390-0
This post hoc analysis provides the first detailed description of the management and outcomes of HZ events in tofacitinib RA and PsA clinical studies.While prior studies have characterised the increased HZ risk with JAKinibs, the clinical management of these events has not been detailed.To this end, Winthrop, et al. analysed data from 21 RA and 3 PsA clinical studies to evaluate how HZ events and their sequelae were clinically managed during the RA and PsA tofacitinib clinical development progra...
Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients
J Clin Rheumatol. 2021;27(8):e482–e490
This post hoc analysis of pooled data from 21 clinical trials in the tofacitinib clinical trial programme highlights the importance of identifying known risk factors of RA-interstitial lung disease (ILD) in clinical practice.Citera, et al. investigated incidence rates of ILD – an extra-articular manifestation of RA – in patients with RA, receiving tofacitinib 5 or 10 mg BID and sort to identify potential risk factors for ILD in these patients....