Expert Opin Drug Saf. 2022. doi: 10.1080/14740338.2022.2100343
It is too early to conclude that the second-generation JAK inhibitors have a lower VTE risk and caution in patients with VTE risk factors is required.
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.
Comparison of drug retention of TNF inhibitors, other biologics and JAK inhibitors in RA patients who discontinued JAK inhibitor therapy
Rheumatology (Oxford) 2022 doi: 10.1093/rheumatology/keac285
Real-world population-based study shows that a switch to a second JAKinib results in a higher drug retention, as compared to switching to a TNFi, in patients with RA who discontinue original JAKinib therapy.
A Retrospective Study of the Efficacy of JAK Inhibitors or Abatacept on Rheumatoid Arthritis-Interstitial Lung Disease
Inflammopharmacology. 2022. Epub ahead of print doi: 10.1007/s10787-022-00936-w
This study of the effectiveness of JAKinibs or abatacept in patients with RA-interstitial lung disease (RA-ILD) shows that treatment is related to stability or improvement of RA-ILD in over 80% of patients.
Nat Rev Rheumatol. 2022 Jan 5:1–13. Epub ahead of print doi: 10.1038/s41584-021-00726-8The development of targeted small-molecule therapies such as JAK inhibitors, which have varied selective inhibitory profiles, has enabled a paradigm shift in the treatment of diverse disorders, to the extent that they could ultimately enable either complete withdrawal or avoidance of glucocorticoid use in some autoimmune diseases, and could have the potential to regulate any active factor inhibiting the transition to cure.In this review paper, Tanaka, et al. describe the progress in JAK-targetin...
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-zSystematic 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...
A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition
Rheumatology (Oxford). 2021. Epub ahead of print. doi: 10.1093/rheumatology/keab740.JAK inhibitors are likely to become an important part of the overall treatment paradigm for spondyloarthritis (SpA).Although not fully understood, the pathogenesis of SpA is complex and thought to involve both environmental and genetic factors that together elicit a chronic inflammatory response involving the innate and adaptive immune systems. Several different cytokines, TNF, IL-17A, IL-12/23 and IL-23, which are directly/indirectly affected by JAK molecules, are involved in the pathogenesis o...
Efficacy and safety of tofacitinib versus baricitinib in patients with rheumatoid arthritis in real clinical practice: analyses with propensity score-based inverse probability of treatment weighting
Ann Rheum Dis. 2021;80(9):1130-1136Propensity score-based inverse probability of treatment weighting shows that efficacy may differ between tofacitinib and baricitinib. Miyazaki, et al. compared the efficacy and safety of the two JAK inhibitors in real-world clinical practice, after reduction to a minimum of the selection bias, using propensity score-based inverse probability of treatment weighting, and adjustment for confounding patient characteristics. They found that tofacitinib may be less effective in patients resistant to m...
Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register
Ann Rheum Dis. 2021 Jul 28:annrheumdis-2021-220651A 3.6-fold increased risk of herpes zoster (HZ) is associated with tsDMARDs, and an increased risk is associated with bDMARDs, compared with csDMARDs. It is now well known that patients with RA have an increased risk of developing herpes zoster (HZ), and that incidence rates appear to be increased with TNF and JAK inhibitors. To this end, Redeker, et al. used data from the German RABBIT Registry to compare event and incidence rates of HZ in patients with RA treated with the three different DMAR...
Contribution of a European-Prevalent Variant Near CD83 and an East Asian-Prevalent Variant Near IL17RB to Herpes Zoster Risk in Tofacitinib Treatment: Results of Genome-Wide Association Study Meta-Analyses
Arthritis Rheumatol. 2021;73(7):1155–66Genetic analysis of tofacitinib-treated subjects with RA or PsO identified multiple loci associated with increased herpes zoster (HZ) risk.It is well known that HZ risk is elevated in subjects with RA compared with the general population, and that treatment with JAK inhibitors may result in increased risks compared with TNFi and other bDMARD treatments. To this end, Bing, et al. used genome-wide association studies to identify genetic factors associated with an increased risk/faster onset of HZ ...