RA Literature Highlights – March 2023
Tofacitinib, Baricitinib, Sarilumab, bDMARDs, tsDMARDs, BSRBR-RA
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.
July 2022
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.
February 2019
Cardiovascular Safety During Treatment with Baricitinib in Rheumatoid Arthritis
Arthritis Rheumatol. 2019 Jul;71(7):1042-1055.
This study indicates no association between exposure to BARI and MACE, arterial thrombotic events (ATE), or congestive heart failure (CHF). Overall IRs for venous thromboembolic event (VTE) in BARI-treated patients falls within the reported range for patients with RA.RA patients have a greater risk of cardiovascular (CV) diseases of arterial ischemic origin, and an increased risk of VTE. Studied frequencies of thromboembolic events in RA populations in the last decade has been reported as 2–3x h...
January 2019
Comparative Risk of Venous Thromboembolism with Tofacitinib versus Tumour Necrosis Factor Inhibitor: A Cohort study of Rheumatoid Arthritis Patients
Desai RJ, et al. Arthritis Rheumatol. 2019 June;71(6):892-900.
Occurrences of venous thromboembolism (VTE) in 50, 865 RA patients initiating Tofacitinib (TOF) or a TNF inhibitor (TNFi) was infrequent. No significant risk of VTE for TOF versus TNFi was observed.Safety concerns of JAK inhibitor BARI include potentially increased risk of VTE at the higher 4 mg dose. It’s unclear if this is attributable to JAK-inhibition and extends to TOF. This study compared the risk of VTE with TOF, versus TNFi in real-world settings with RA patients.RA patients initiating T...
October 2018
Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment
J Rheumatol. 2019 Jan;46(1):7-18. DOI: 10.3899/jrheum.171361
Baricitinib (BARI) showed an acceptable 5.5-year safety profile in this integrated analysis of patients with moderate-to-severe, active RA.This study evaluated the safety profile of the oral, once daily Janus kinase inhibitor, BARI, in adults with moderately to severely active RA. Data from eight randomised clinical trials and one long-term extension study were pooled and analysed for placebo comparison and dose response.There were 3492 patients who received BARI for a total of 6637 patient-yea...
July 2018
Thromboembolism with Janus Kinase (JAK) Inhibitor for Rheumatoid Arthritis: How Real is the Risk?
Drug Safety 2018 Jul;41(7):645–53
Current data suggests that JAK inhibitors may increase the risk of thromboembolism and pulmonary thrombosis (PT) in RA.Two JAK inhibitors – baricitinib (BARI) and tofacitinib (TOF) – are considered effective treatments for RA, however, there are concerns about the thromboembolic risks associated with them. In August 2017, the summary of product characteristics for BARI was revised to include a warning of developing DVT and pulmonary embolism (PE), with recommendations that BARI should be used wi...
May 2018
Analysis of Spontaneous Postmarket Case Reports Submitted to the FDA Regarding Thromboembolic Adverse Events and JAK Inhibitors
Drug Saf 2018 Apr; 41(4):357–61 DOI: 10.1007/s40264-017-0622-2
Thromboembolic-related adverse events (AEs) were, in general, not considered a class-wide safety concern after analysis of tofacitinib (TOF) and ruxolitinib (RUX) clinical data, though pulmonary thrombosis is considered a potential class-wide safety issue and portal vein thrombosis was considered a potential safety issue for RUX. During analysis of baricitinib (BARI) clinical trial data, the FDA expressed concerns regarding thromboembolic events. Following this, the CHMP have recently added a pr...