Bayesian network meta-analysis of randomised controlled trials (RCTs) highlights the effectiveness of secukinumab, ixekizumab, and tofacitinib in patients with psoriatic arthritis (PsA) and an inadequate response to tumour necrosis factor inhibitors (TNFi).There is a current need for therapies with alternative mechanisms of actions to DMARDs and TNFi, for the significant proportion of patients with PsA who insufficiently respond to these therapies. While RCTs for therapies such as secukinumab a...
Long-term evaluation of tofacitinib has found limited progression of structural damage in patients with RA treated with tofacitinib for up to 5 years. Similar results were also observed for patients receiving tofacitinib monotherapy or combination therapy for up to 3 years.It is well known that inflammation in RA leads to structural damage over time, and therapies such as DMARDS have the ability to reduce inflammation whilst inhibiting the progression of structural damage. In this study, van der...

April 2021

Risk of venous thromboembolism associated with tofacitinib in patients with rheumatoid arthritis: a population-based cohort study

Rheumatology (Oxford). 2021 Mar 22:keab294. Epub ahead of print. DOI: 10.1093/rheumatology/keab294

A population-based cohort study of 87,653 RA patients has found no evidence for an increased risk of venous thromboembolism (VTE) for tofacitinib, versus TNFis, in patients with RA.The introduction of JAKinibs, almost a decade ago, has provided an important oral option for the treatment of RA. However, in recent years, a safety concern, relating to incidence of VTE after treatment, has emerged. Consequently, both the US and European regulatory authorities now recommend caution for use of tofacit...

JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib

Ann Rheum Dis. 2021 Mar 19:annrheumdis-2020-219012. Epub ahead of print. DOI: 10.1136/annrheumdis-2020-219012

The first study to combine in vitro inhibition of cytokine responses in whole blood with clinical pharmacokinetics of individual JAKinibs to model daily cytokine-mediated pharmacodynamic profiles in healthy individuals and patients with RA, has demonstrated that JAKinib potencies depended on cytokine stimulus, pSTAT readout and cell type.Traves and colleagues have observed that JAKinibs have unique, differential effects on specific cytokine signalling pathways, dependent on cytokine stimulus, ST...

March 2021

Thought to be the first study of its kind, Hamar, et al. have demonstrated the effect of one-year tofacitinib treatment on bone mineral density (BMD) in RA patients. While the association between RA and osteoporosis is well known, and evidence indicates that up to 70% of these patients have reduced BMD, little information is available on how the JAK inhibitor tofacitinib affects bone status, areal and volumetric BMD, and bone turnover markers. In this prospective study, 30 patients were assessed...
Analysis from the US Corrona RA registry has provided the longest-term real-world safety data for a JAK inhibitor to date. The analysis showed that the cohorts had similar adverse events, except for higher herpes zoster rates for tofacitinib initiators vs bDMARDs.Kremer JM, et al. analysed adult patients with RA newly initiating tofacitinib, or a bDMARD, to compare incidence rates of MACE, SIEs, HZ, malignancies and death. VTE data were also collected prospectively and assessed descriptively thr...

January 2021

Considering the multi-domain nature of PsA, effective treatments must demonstrate efficacy across a range of clinical and patient-reported outcomes. Dermatologic symptoms often precede rheumatic manifestations in people with PsA, typically by 10 years. Tofacitinib demonstrated significant improvements across a range of outcomes including burdensome dermatologic symptoms. This post hoc analysis included data from two double-blind, Phase 3 studies in patients with active PsA and an inadequate resp...