JAK/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic arthritis

Clin Exp Rheumatol. 2021;39(3):668-675.

Crispino N,

Ciccia F.

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...

Keywords:

• JAK,
• Basic Science,
• MOA

Tofacitinib versus tocilizumab in the treatment of biological-naïve or previous biological-failure patients with methotrexate-refractory active rheumatoid arthritis

RMD Open. 2021;7(2):e001601.

Mori S,

Urata Y,

Yoshitama T,

Ueki Y.

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...

Keywords:

• JAK,
• IL-6,
• Tofacitinib,
• Tocilizumab,
• Efficacy,
• Safety

Efficacy of baricitinib in patients with moderate-to-severe rheumatoid arthritis with 3 years of treatment: results from a long-term study

Rheumatology (Oxford). 2021;60(5):2256-2266.

Smolen JS,

Xie L,

Jia B,

Taylor PC,

Burmester G,

Tanaka Y,

Elias A,

Cardoso A,

Ortmann R,

Walls C,

Dougados M.

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 ...

Keywords:

• JAK,
• Baricitinib,
• LTE,
• Efficacy

Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects

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

Estupiñán HY,

Berglöf A,

Zain R,

Smith CIE

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...

Keywords:

• BTK,
• MOA,
• Review

Post-Approval Comparative Safety Study of Tofacitinib and Biological Disease-Modifying Antirheumatic Drugs: 5-Year Results from a United States–Based Rheumatoid Arthritis Registry

ACR Open Rheumatol. 2021 Feb 11.

Kremer JM,

Bingham CO 3rd,

Cappelli LC,

Greenberg JD,

Madsen AM,

Geier J,

Rivas JL,

Onofrei AM,

Barr CJ,

Pappas DA,

Litman HJ,

Dandreo KJ,

Shapiro AB,

Connell CA,

Kavanaugh A

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...

Keywords:

• JAK,
• Tildrakizumab,
• Real-World

Which Patient-reported Outcomes do Rheumatology Patients Find Important to Track Digitally? A Real-world Longitudinal Study in Arthritis Power

Arthritis Res Ther. 2021;23(1):53.

Nowell WB,

Gavigan K,

Kannowski CL,

Cai Z,

Hunter T,

Venkatachalam S,

Birt J,

Workman J,

Curtis JR

Fatigue, physical function, pain, and morning joint stiffness are the most important PROs to track, according to the rheumatology patients who experience these symptoms. Increasingly used, alongside clinical measures, to track symptoms and assess disease activity over time, patient-reported outcomes (PROs) are also important indicators of quality of life and treatment effectiveness. To enable us to better understand which PROs patients with rheumatic and musculoskeletal disease consider most imp...

Keywords:

• PRO / QoL,
• Real-World

The JAK/STAT Pathway: A Focus on Pain in Rheumatoid Arthritis

Semin Arthritis Rheum. 2021 Feb;51(1):278-284

Simon LS,

Taylor PC,

Choy EH,

Sebba A,

Quebe A,

Knopp KL,

Porreca F

Many cytokines associated with RA pathogenesis and pain are affected directly or indirectly by the JAK/STAT pathway, therapeutic targeting may offer promise. Having better understanding of these mechanisms can help clinicians make treatment decisions that optimise the control of inflammation and pain. However, pain in patients with RA is complex and involves multiple driving mechanisms that may differentially occur over time in different people. Although one known constant is that nociceptive ac...

Keywords:

• JAK,
• Basic Science,
• Review

Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2

Annals of the rheumatic diseases. 2021 Mar 1;80(3):312-20.

Mease PJ,

Lertratanakul A,

Anderson JK,

Papp K,

Van den Bosch F,

Tsuji S,

Dokoupilova E,

Keiserman M,

Wang X,

Zhong S,

McCaskill RM,

Zueger P,

Pangan AL,

Tillett W

In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA. Despite the availability of bDMARDs in PsA, only a small proportion of patients achieve the recommended target of minimal disease activity; as such, additional treatment options are needed. Upadacitinib is under evaluation for PsA. This paper reports the 24-week data ...

Keywords:

• JAK,
• Upadacitinib,
• Phase 3

Tofacitinib in psoriatic arthritis patients: skin signs and symptoms and health-related quality of life from two randomized Phase 3 studies

J Eur Acad Dermatol Venereol 2020;34:2809–2820.

Merola JF,

Papp KA,

Nash P,

Gratacós J,

Boehncke W-H,

Thaçi D,

Graham D,

Hsu M-A,

Wang C,

Wu J,

Young P

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...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• PRO / QoL,
• Skin

EULAR Definition of Difficult-to-Treat Rheumatoid Arthritis

Ann Rheum Dis 2021;80:31–35.

Nagy G,

Roodenrijs NMT,

Welsing PMJ,

Kedves M,

Hamar A,

van der Goes MC,

Kent A,

Bakkers M,

et al.

A significant proportion of people with RA remain symptomatic despite treatment according to current management recommendations. Different terms have traditionally been used to describe this subpopulation, including severe, refractory, resistant to multiple drugs or treatments, established and difficult-to-treat. A recent survey indicated that – in addition to new drugs – new management approaches are needed for optimal treatment in these patients.A EULAR Task Force agreed the uniform terminolog...

Keywords:

• EULAR