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...
Analysis of data over 56 weeks shows that efficacy responses are maintained with upadacitinib 15 mg and 30 mg.Following the publication of 12-week data from the Phase III, randomised double-blind, SELECT-PsA 1 study, earlier this year, McInnes, et al. now report the 56-week efficacy and safety data of upadacitinib 15 mg and 30 mg in patients with PsA and an inadequate response to non-biological therapyEfficacy responses and inhibition of radiographic progression were maintained with upadacitinib...

October 2021

Oral baricitinib maintained lower levels of radiographic progression than initial csDMARD or placebo through 5 years in patients with active RA.It is well known that persistent joint inflammation in RA can lead to irreversible structural damage that impacts on patient physical function and quality-of-life. To this end, van der Heijde, et al. evaluated the effect of baricitinib on inhibiting radiographic progression of structural joint damage over 5 years in patients with active RA. Results from ...
Propensity 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...
Tofacitinib could induce Hepatitis B virus (HBV) reactivation in RA patients.With previous studies having already demonstrated that RA patients using biologic agents, might experience HBV reactivation leading to acute hepatitis, hyperbilirubinemia, and death, Wang, et al. aimed to investigate HBV reactivation in patients with RA receiving tofacitinib. They found that Hepatitis B surface antigen positive patients receiving tofacitinib have a high incidence rate of HBV reactivation, which could be...
A 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...

September 2021

Post hoc analysis of the phase III FINCH study shows that filgotinib may be an alternative treatment option for patients with RA who have poor prognostic factors (PPFs), especially those not responding to standard treatment such as methotrexate (MTX).PPFs are associated with severe disease and risk for disease progression in patients with RA. Consequently, the 2019 EULAR management guidelines for RA recommend early treatment escalation for patients with PPFs who have inadequate response to first...
Real-world evidence suggests that monotherapy and combination therapy tofacitinib is an effective intervention in RA with persistence and effectiveness comparable to bDMARDs. Despite recommendations from EULAR that bDMARDs and tsDMARDs be used in combination with csDMARDs for the treatment of RA, it is estimated that up to a third of patients take their medication as monotherapy.This post hoc analysis of data from the Australian OPAL study by Bird, et al. aimed to describe the real-world effecti...

August 2021

Genetic 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 ...
In a real-world setting, tofacitinib and baricitinib have comparable continuing efficacies and safety profiles in patients with RA.It is important to determine the differences and similarities of JAK inhibitors in a real-world setting so that the optimal agent can be administered. However, until now, no published data of a direct comparison among these agents in RA have been available. With this in mind, Iwamoto, et al. compared the efficacy and safety of tofacitinib with those of baricitinib by...