May 2022

Treatment of axial spondyloarthritis: an update

Nat Rev Rheumatol. 18, 205–216 (2022) 2022 doi: 10.1038/s41584-022-00761-z

In this review Danve and Deodhar report an update on modern axSpa treatment. They found that in the past two decades substantial progress in the diagnosis and management of axSpA has been witnessed. Whilst ASAS classification criteria have enabled earlier diagnosis the increased availability of novel therapies, evolving drug safety data and novel clinical trials have allowed clinicians to rethink the placement and timing of drugs in disease management.

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Immune‑related adverse events (irAEs) in ankylosing spondylitis (AS) patients treated with interleukin (IL)‑17 inhibitors: a systematic review and meta‑analysis

Inflammopharmacology. 2022, Apr;30(2):435-451. doi: 10.1007/s10787-022-00933-z

The most common immune system-related AEs in patients treated with IL-17 inhibitors are mucosal and opportunistic infections.

Interleukin (IL)-17 inhibitors are a series of biological drugs used to treat a number of conditions, including ankylosing spondylitis, a disease characterised by immune system dysregulation and joint inflammation. Azadeh, et al. aimed to assess the risk of immune system-related AEs due to targeting IL-17 or IL-17R.

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March 2022

The effect of secukinumab on patient-reported outcomes in patients with active psoriatic arthritis in a randomised phase 3 trial

Lancet. 2022. Epub ahead of print

Predefined analysis of FUTURE 5, the largest Phase 3 randomised trial of secukinumab in patients with PsA to date, demonstrates that secukinumab results in early, statistically significant, clinically meaningful, sustained improvements in PROs across all doses, compared with placebo.The fully human anti-interleukin 17A monoclonal antibody, secukinumab has shown clinical and radiographical efficacy in patients with PsA, yet the clinical significance of improvements across a wide variety of PROs r...

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November 2021

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...

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July 2021

Bimekizumab versus adalimumab in plaque psoriasis

N Engl J Med 2021; 385:130–41. doi: 10.1056/NEJMoa2102388

Bimekizumab was noninferior and superior to adalimumab with respect to PASI 90 response and IGA score at Week 16. Bimekizumab is a promising IL-17A/F inhibitor that has shown clinical improvement in PsO patients compared to placebo and other IL inhibitors. Warren et al. compared the safety and efficacy of bimekizumab with adalimumab in a 56-week double-blind trial.

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May 2021

Comparative efficacy and safety of secukinumab, ixekizumab, and tofacitinib in patients with active psoriatic arthritis showing insufficient response to tumor necrosis factor inhibitors

Int J Clin Pharmacol Ther. 2021. Epub ahead of print.

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...

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February 2021

Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, double-blind, placebo-controlled, randomised withdrawal Phase 3 trial

https://pubmed.ncbi.nlm.nih.gov/33549192/

Bimekizumab therapy was associated with a rapid and sustained improvement in PASI response and IGA score in patients with moderate to severe plaque psoriasis. Dual inhibition of IL-17A/F with bimekizumab can affect a more durable response in PsO patients than sole IL-17A inhibition. Gordon et al. compared the safety and efficacy of two different maintenance dosing schedules, in addition to the effects of treatment withdrawal in the 52-week BE READY trial.

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July 2017

Pathogenetic Insights from the Treatment of Rheumatoid Arthritis

Lancet 2017;389:2328–37 DOI 10.1016/S0140-6736(17)31472-1

This review paper examines the understanding gained from looking at the effects of specific immune interventions in the treatment of RA.The introduction of novel IL-6 agents has provided the ideal opportunity to explore the distinct effect of cytokine inhibition, as opposed to receptor inhibition, at the molecular level. Mechanistic insights into TNF could also be obtained in the future with advanced molecular and informatics approaches, and future biopsy studies will be important to explore the...

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October 2015

Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibition

Annals of the Rheumatic Diseases. 2015 Sep 9. doi:10.1136/annrheumdis-2014-207201

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis (Ps) and characterised by synovitis and progressive destruction of articular cartilage and bone. Recently developed agents for PsA target IL12p40, IL-6 and IL-17, several of which signal through the JAK family of receptor-associated tyrosine kinases. Tofacitinib is a drug of the JAK inhibitor class and is currently approved for the treatment of RA in 27 countries. This study evaluated the effect of tofacitini...

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Phase 3 studies comparing brodalumab with ustekinumab in psoriasis

N Engl J Med 2015;373:1318–28. doi: 10.1056/NEJMoa1503824

Brodalumab treatment resulted in a rapid reduction in the signs and symptoms of PsO. The median time to a PASI 75 response with 210 mg of brodalumab Q2W was 4 weeks, approximately twice as fast as the median time to a response with ustekinumab.

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