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...

July 2021

Fifty-six-week data suggest that upadacitinib could be a favourable long-term treatment option in patients with PsA who are refractory to biologic therapy.As the need for additional therapeutic agents that can effectively control disease activity continues, new data from a 56-week analysis of the oral reversible JAK1 inhibitor, upadacitinib, currently under investigation for the treatment of PsA, shows that efficacy of the drug is maintained over the duration of this study.Mease, et al. explored...
Results from the COVID-19 Global Rheumatology Alliance physician registry show that people with RA using rituximab or JAKi, at COVID-19 onset, are more likely to experience poor COVID-19 outcomes, ranging from hospitalisation to death, compared with use of TNFi.The ongoing COVID-19 pandemic has had a significant impact on people with RA, many of whom are treated with b/tsDMARDs. To help address some of the knowledge gaps around the influence of b/tsDMARDs on COVID-19 outcomes, Sparks, et al. ana...
The influence of inflammation on patient global assessment (PGA) improvements differs between baricitinib and tocilizumab differs. Adequate PGA improvement remains one of the unmet needs in current RA treatment.Asai, et al. compared the effects of baricitinib and tocilizumab on disease activity in patients with RA while investigating the influence of inflammation on PGA improvement.Using data from a multicentre registry, 48 propensity-matched pairs of patients, who had been observed for longer t...

June 2021

The JAK/STAT pathway is receiving increasing attention in modulation of nociceptive responses, given its clear role in cytokine signalling. The authors of this review speculate that JAKinibs may have an effect on the modulation of nociception and reduction of pain.Crispino N, et al. review the impact of pain in patients with rheumatic disease and the physiological basis of modulating nociceptive pain. They examine the role of cytokines in the modulation of pain and analyse current clinical JAKin...
Findings from a multicentre cohort study in Japan provide important information that is expected to aid in determining the position of tofacitinib in the treatment algorithm for RA.Mori S, et al. compared therapeutic outcomes, from real-world registries, at 12 months between tofacitinib-treated and tocilizumab-treated patients to clarify whether tofacitinib should only be considered as an option for patients who have either failed to respond to at least one bDMARD or are MTX-resistant/-intoleran...
Baricitinib 4mg may be considered for long-term treatment of early and refractory rheumatoid arthritis following results demonstrating efficacy and tolerability for up to 3 years.Smolen JS, et al. analysed data from two completed 52-week, phase III studies, RA-BEGIN (DMARD-naïve) and RA-BEAM (MTX-IR), and one ongoing long-term extension study (RA-BEYOND) – providing data for 148 weeks in total. Results demonstrated that the long-term maintenance of clinically relevant treatment goals, including ...

April 2021

Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects

Front. Cell Dev. Biol. 9:630942 DOI: 10.3389/fcell.2021.630942

Understanding of the B-cell receptor signalling pathway led to the identification of a suitable drug target to addresses autoimmunity and inflammation in areas such as MS, RA, pemphigus and SLE. There are currently 22 BTKis in various stages of clinical development. However, AEs such as cardiovascular and bleeding side effects, as well as rash, diarrhoea and infections have been associated with the inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain.Based on clinic...

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March 2021

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...