Treatment of Axial Spondyloarthritis: What Does the Future Hold?

Poddubnyy, Denis; Sieper, Joachim

doi:10.1007/s11926-020-00924-5

Cited by 21 publications

(12 citation statements)

References 54 publications

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“…In fact, for more than 15 years, TNF-α inhibitors were the only biologic treatment available and, despite an initial great success in SpA management, it came out clearly that almost 40% of patients failed to reach a significative response. The new therapeutic agents interfering with the IL-23/IL-17 axis can be divided into monoclonal antibodies directly targeting IL-17, IL-23 or their receptors and small molecules inhibiting the intracellular pathways triggered by these cytokines ( 134 ).…”

Section: Reviewmentioning

confidence: 99%

Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview

Schinocca¹,

Rizzo²,

et al. 2021

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Interleukin-23 (IL-23) is a pro-inflammatory cytokine composed of two subunits, IL-23A (p19) and IL-12/23B (p40), the latter shared with Interleukin-12 (IL-12). IL-23 is mainly produced by macrophages and dendritic cells, in response to exogenous or endogenous signals, and drives the differentiation and activation of T helper 17 (Th17) cells with subsequent production of IL-17A, IL-17F, IL-6, IL-22, and tumor necrosis factor α (TNF-α). Although IL-23 plays a pivotal role in the protective immune response to bacterial and fungal infections, its dysregulation has been shown to exacerbate chronic immune-mediated inflammation. Well-established experimental data support the concept that IL-23/IL-17 axis activation contributes to the development of several inflammatory diseases, such as PsA, Psoriasis, Psoriatic Arthritis; AS, Ankylosing Spondylitis; IBD, Inflammatory Bowel Disease; RA, Rheumatoid Arthritis; SS, Sjogren Syndrome; MS, Multiple Sclerosis. As a result, emerging clinical studies have focused on the blockade of this pathogenic axis as a promising therapeutic target in several autoimmune disorders; nevertheless, a greater understanding of its contribution still requires further investigation. This review aims to elucidate the most recent studies and literature data on the pathogenetic role of IL-23 and Th17 cells in inflammatory rheumatic diseases.

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Section: Reviewmentioning

confidence: 99%

Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview

Schinocca¹,

Rizzo²,

et al. 2021

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“…Janus kinase inhibitors (JAKi) (tofacitinib, upadacitinib, filgotinib) are currently in development in axSpA, but upadacitinib has recently been approved for the treatment of axSpA. During the phase 3 clinical trials, there was no safety signal regarding CV events with JAKi in patients with axSpA ( 63 ). In a systematic review and meta-analysis of the CV effects of JAKi in patients with RA in randomized controlled trials, there was no evidence of a significant change in CV risk in the short term ( 64 ).…”

Section: The Effect Of Treatment On Cardiovascular Risk In Axspamentioning

confidence: 99%

The Risk of Cardiovascular Diseases in Axial Spondyloarthritis. Current Insights

Toussirot

2021

Front. Med.

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There is an increased cardiovascular (CV) risk in axial spondyloarthritis (axSpA), leading to increased CV mortality and morbidity in these patients. The factors that may explain this enhanced CV risk in axSpA are multiple, including traditional CV risk factors such as smoking, but also the inflammatory process and probably the use of non-steroidal anti-inflammatory drugs (NSAIDs). The CV involvement of axSpA may be detected at an early and pre-clinical stage, using non-invasive techniques. While NSAIDs play a deleterious role in the CV risk of axSpA, TNF inhibitors seem to have a beneficial impact, but this remains to be demonstrated in specific clinical studies. More data are needed to determine the potential effects of IL-17 inhibitors on the CV risk of axSpA. CV comorbidity has been mainly assessed in the radiographic form of axSpA, while limited data are available in patients with the non-radiographic form. The current management of axSpA must consider this CV comorbidity according to the EULAR recommendations. Rheumatologists play a determinant role in the detection of CV risk and current management of these patients is focused on the control of disease activity, suppression of inflammation, screening for and management of traditional CV risk factors, as well as the restriction of NSAID use.

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“…Ankylosing spondylitis (AS), also called radiographic axial spondyloarthritis, 1 is a chronic inflammatory disease of the axial skeleton that can result in serious impairment of spinal mobility and reduced quality of life. [2][3][4] The incidence of AS is 0.4-15.0 per 100 000 patient-years, varying by region. 5 The Assessment of SpondyloArthritis international Society (ASAS)/European League Against Rheumatism and American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network treatment guidelines recommend several pharmacological treatments for AS management as well as physical therapy.…”

Section: Introductionmentioning

confidence: 99%

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study

et al. 2021

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ObjectiveTo assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS).MethodsThis phase III, randomised, double-blind, placebo-controlled study enrolled patients aged ≥18 years diagnosed with active AS, meeting the modified New York criteria, with centrally read radiographs, and an inadequate response or intolerance to ≥2 non-steroidal anti-inflammatory drugs. Patients were randomised 1:1 to receive tofacitinib 5 mg two times per day or placebo for 16 weeks. After week 16, all patients received open-label tofacitinib until week 48. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society ≥20% improvement (ASAS20) and ≥40% improvement (ASAS40) responses, respectively, at week 16. Safety was assessed throughout.Results269 patients were randomised and treated: tofacitinib, n=133; placebo, n=136. At week 16, the ASAS20 response rate was significantly (p<0.0001) greater with tofacitinib (56.4%, 75 of 133) versus placebo (29.4%, 40 of 136), and the ASAS40 response rate was significantly (p<0.0001) greater with tofacitinib (40.6%, 54 of 133) versus placebo (12.5%, 17 of 136). Up to week 16, with tofacitinib and placebo, respectively, 73 of 133 (54.9%) and 70 of 136 (51.5%) patients had adverse events; 2 of 133 (1.5%) and 1 of 136 (0.7%) had serious adverse events. Up to week 48, with tofacitinib, 3 of 133 (2.3%) patients had adjudicated hepatic events, 3 of 133 (2.3%) had non-serious herpes zoster, and 1 of 133 (0.8%) had a serious infection; with placebo→tofacitinib, 2 (1.5%) patients had non-serious herpes zoster. There were no deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections.ConclusionsIn adults with active AS, tofacitinib demonstrated significantly greater efficacy versus placebo. No new potential safety risks were identified.Trial registration numberNCT03502616

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Treatment of Axial Spondyloarthritis: What Does the Future Hold?

Cited by 21 publications

References 54 publications

Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview

Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview

The Risk of Cardiovascular Diseases in Axial Spondyloarthritis. Current Insights

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study

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