Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naïve active psoriatic arthritis patients with physician-reported spondylitis: pooled results from two phase 3, randomised, controlled trials

Helliwell, Philip S.; Gladman, Dafna D.; Chakravarty, Soumya D.; Kafka, Shelly; Karyekar, Chetan S.; Yin, You; Campbell, Kim; Sweet, Kristen; Kavanaugh, Arthur; Gensler, Lianne S.

doi:10.1136/rmdopen-2019-001149

Cited by 42 publications

(34 citation statements)

References 30 publications

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“…To date, according to the EULAR recommendations [62], if axial disease predominates and presents insufficient response to non-steroidal anti-inflammatory drugs, treatment with TNF inhibitor or IL-17A inhibitor should be considered. Furthermore, IL12/23 inhibitor, such as ustekinumab and IL23 inhibitor, such as risankizumab, did not prove clinical efficacy in axial disease [64][65][66]. Thus, more studies are needed to clarify why a drug that inhibits IL23, which acts upstream from IL17, presents no clear clinical efficacy in axial disease, whilst having a good effect in psoriasis [67].…”

Section: Discussionmentioning

confidence: 99%

Axial Psoriatic Disease: Clinical and Imaging Assessment of an Underdiagnosed Condition

Giovannini

Zabotti

Cicciò

et al. 2021

JCM

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The frequent involvement of the spine and sacroiliac joint has justified the classification of psoriatic arthritis (PsA) in the Spondyloarthritis group. Even if different classification criteria have been developed for PsA and Spondyloarthritis over the years, a well-defined distinction is still difficult. Although the majority of PsA patients present peripheral involvement, the axial involvement needs to be taken into account when considering disease management. Depending on the definition used, the prevalence of axial disease may vary from 25 to 70% in patients affected by PsA. To date, no consensus definition has been reached in the literature and the definition of axial involvement in PsA has varied from isolated sacroiliitis to criteria used in ankylosing spondylitis. This article reviews the unmet needs in the clinical and radiological assessment of axial PsA, reporting the various interpretations of axial involvement, which have changed over the years. Focusing on both imaging and clinical standpoints, we reported the prevalence of clinical and radiologic features, describing the characteristics of axial disease detectable by X-rays, magnetic resonance imaging, and PET-CT, and also describing the axial symptoms and outcome measures in patients affected by axial disease.

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Section: Discussionmentioning

confidence: 99%

Axial Psoriatic Disease: Clinical and Imaging Assessment of an Underdiagnosed Condition

Giovannini

Zabotti

Cicciò

et al. 2021

JCM

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“…Ustekinumab, a human IgG1κ monoclonal antibody that binds to the p40 subunit common to IL-12 and IL-23, was approved for the treatment of PsA in 2013 [ 126 ]. Studies have shown that agents that reduce p19 binding to IL-23R may be used to inhibit IL-23 in inflammation, thus inhibiting the p19/IL-23-associated inflammation axis [ 127 ].…”

Section: Interleukin-23mentioning

confidence: 99%

Effect of interleukin-6, -17, -21, -22, and -23 and STAT3 on signal transduction pathways and their inhibition in autoimmune arthritis

Woś

Tabarkiewicz

2021

Immunol Res

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Rheumatic diseases are complex autoimmune diseases which include among others rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and psoriatic arthritis (PsA). These diseases are characterized by prolonged and increased secretion of inflammatory factors, eventually leading to inflammation. This is often accompanied by persistent pain and stiffness in the joint and finally bone destruction and osteoporosis. These diseases can occur at any age, regardless of gender or origin. Autoimmune arthritis is admittedly associated with long-term treatment, and discontinuation of medication is associated with unavoidable relapse. Therefore, it is important to detect the disease at an early stage and apply appropriate preventative measures. During inflammation, pro-inflammatory factors such as interleukins (IL)-6, -17, -21, -22, and -23 are secreted, while anti-inflammatory factors including IL-10 are downregulated. Research conducted over the past several years has focused on inhibiting inflammatory pathways and activating anti-inflammatory factors to improve the quality of life of people with rheumatic diseases. The aim of this paper is to review current knowledge on stimulatory and inhibitory pathways involving the signal transducer and activator of transcription 3 (STAT3). STAT3 has been shown to be one of the crucial factors involved in inflammation and is directly linked with other pro-inflammatory factors and thus is a target of current research on rheumatoid diseases.

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“…Ustekinumab is a human monoclonal antibody that binds to the p40 subunit that is shared by both IL-12 and IL-23 and inhibits the functions of both IL-12 and IL-23. In three clinical trials in patients with PsA, ustekinumab treatment demonstrated higher improvement of the disease activity [ 99 , 100 , 101 ]. Following these results, ustekinumab received FDA approval for the treatment of PsA in 2013.…”

Section: Il-23/il-17 Axis-targeting Therapiesmentioning

confidence: 99%

The Role of the IL-23/IL-17 Pathway in the Pathogenesis of Spondyloarthritis

Tsukazaki

Kaito

2020

IJMS

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Spondyloarthritis (SpA) is a subset of seronegative rheumatic-related autoimmune diseases that consist of ankylosing spondylitis (AS), psoriatic spondylitis (PsA), reactive spondylitis (re-SpA), inflammatory bowel disease (IBD)-associated spondylitis, and unclassifiable spondylitis. These subsets share clinical phenotypes such as joint inflammation and extra-articular manifestations (uveitis, IBD, and psoriasis [Ps]). Inflammation at the enthesis, where ligaments and tendons attach to bones, characterizes and distinguishes SpA from other types of arthritis. Over the past several years, genetic, experimental, and clinical studies have accumulated evidence showing that the IL-23/IL-17 axis plays a critical role in the pathogenesis of SpA. These discoveries include genetic association and the identification of IL-23- and IL-17-producing cells in the tissue of mouse models and human patients. In this review, we summarize the current knowledge of the pathomechanism by focusing on the IL-23/IL-17 pathway and examine the recent clinical studies of biological agents targeting IL-23 and IL-17 in the treatment of SpA.

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Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naïve active psoriatic arthritis patients with physician-reported spondylitis: pooled results from two phase 3, randomised, controlled trials

Cited by 42 publications

References 30 publications

Axial Psoriatic Disease: Clinical and Imaging Assessment of an Underdiagnosed Condition

Axial Psoriatic Disease: Clinical and Imaging Assessment of an Underdiagnosed Condition

Effect of interleukin-6, -17, -21, -22, and -23 and STAT3 on signal transduction pathways and their inhibition in autoimmune arthritis

The Role of the IL-23/IL-17 Pathway in the Pathogenesis of Spondyloarthritis

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