Anti-IL17A in Axial Spondyloarthritis—Where Are We At?

Cheung, Peter

doi:10.3389/fmed.2017.00001

Cited by 23 publications

(25 citation statements)

References 47 publications

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“…Both TNF-α [ 58 ] and interleukin-17 inhibitors [ 59 ] have been shown to reduce inflammation and improve symptoms in patients with AS [ 60 ]. Furthermore, increased levels of TNF-α, IL-17, IL-23, IL-1β, and IL-6 have been found in sera and synovial fluid from AS patients [ 61 – 64 ].…”

Section: Discussionmentioning

confidence: 99%

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

et al. 2018

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BackgroundAnkylosing spondylitis (AS) results from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the heritability of AS.MethodsUsing a candidate gene approach in this case-control study, 51 mainly functional single nucleotide polymorphisms (SNPs) in genes regulating inflammation were assessed in 709 patients with AS and 795 controls. Data on the patients with AS were obtained from the DANBIO registry where patients from all of Denmark are monitored in routine care during treatment with conventional and biologic disease modifying anti-rheumatic drugs (bDMARDs).The results were analyzed using logistic regression (adjusted for age and sex).ResultsNine polymorphisms were associated with risk of AS (p < 0.05). The polymorphisms were in genes regulating a: the TNF-α pathway (TNF -308 G > A (rs1800629), and − 238 G > A (rs361525); TNFRSF1A -609 G > T (rs4149570), and PTPN22 1858 G > A (rs2476601)), b: the IL23/IL17 pathway (IL23R G > A (rs11209026), and IL18–137 G > C (rs187238)), or c: the NFkB pathway (TLR1 743 T > C (rs4833095), TLR4 T > C (rs1554973), and LY96–1625 C > G (rs11465996)).After Bonferroni correction the homozygous variant genotype of TLR1 743 T > C (rs4833095) (odds ratios (OR): 2.59, 95% confidence interval (CI): 1.48–4.51, p = 0.04), and TNFRSF1A -609 G > T (rs4149570) (OR: 1.79, 95% CI: 1.31–2.41, p = 0.01) were associated with increased risk of AS and the combined homozygous and heterozygous variant genotypes of TNF -308 G > A (rs1800629) (OR: 0.56, 95% CI: 0.44–0.72, p = 0.0002) were associated with reduced risk of AS.ConclusionWe replicated associations between AS and the polymorphisms in TNF (rs1800629), TNFRSF1A (rs4149570), and IL23R (rs11209026). Furthermore, we identified novel risk loci in TNF (rs361525), IL18 (rs187238), TLR1 (rs4833095), TLR4 (rs1554973), and LY96 (rs11465996) that need validation in independent cohorts. The results suggest that genetically determined high activity of the TNF-α, IL23/IL17, and NFkB pathways increase risk of AS.

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Section: Discussionmentioning

confidence: 99%

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

et al. 2018

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“…The only other biologic currently approved for the treatment of AS is secukinumab, a monoclonal antibody directed against interleukin (IL)-17A [ 54 ]. Trials have shown the drug to be symptomatically effective compared with placebo [ 55 ].…”

Section: Tnf Inhibitorsmentioning

confidence: 99%

“…Trials have shown the drug to be symptomatically effective compared with placebo [ 55 ]. Secukinumab has not been studied in nr-axSpA, nor are there any data available on its comparative efficacy relative to TNF inhibitors [ 54 ]. At this time, the ASAS recommendations are to treat with a TNF inhibitor after failure of two NSAIDs and to use it for at least 12 weeks [ 3 ].…”

Section: Tnf Inhibitorsmentioning

confidence: 99%

Nonradiographic axial spondyloarthritis: clinical and therapeutic relevance

Ghosh

Ruderman

2017

Arthritis Res Ther

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Current classification criteria for axial spondyloarthritis (axSpA) provide for the inclusion of patients with a wide range of presentations and manifestations. While not considered a formal subclassification, patients are often divided into radiographic or nonradiographic axSpA based on the presence or absence of radiographic sacroiliitis. This review will focus on nonradiographic axSpA and will discuss clinical manifestations of disease that distinguish, or in many cases do not distinguish, this entity from other individuals with axSpA. This review will also cover treatment paradigms for nonradiographic axSpA, particularly the use of biologic therapies, where current data suggest that nonradiographic disease should be managed largely the same as radiographic disease, or classical ankylosing spondylitis.

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“…Secukinumab, a fully human monoclonal antibody against IL-17A, is the first non-TNF-α inhibitor agent approved for AS, which opens up a therapeutic step of other cytokine targets beyond TNF (18). The benefits of secukinumab are generally seen regardless of whether patients were naive or not to TNF inhibitor therapy, and were persistent up to 5 years treatment; secukinumab was also associated with visible improvement of mobility and physical function, quality of life and work productivity in some of the trials (19).…”

Section: Immunopathogenesis Of Ankylosing Spondylitismentioning

confidence: 99%

New insights into IL‑17/IL‑23 signaling in ankylosing spondylitis (Review)

et al. 2020

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Ankylosing spondylitis (AS) is a progressive common autoimmune inflammatory disease, part of the spondylarthritis group, characterized, besides clinical spinal and peripheral joint inflammation, by enthesitis and new bone formation, that can lead to severe functional impairment. Beyond intensive and continuous research on the pathogenic process extensively performed in recent years, their impact on therapeutic management remains open to future development. Better knowledge of AS pathogenesis have shown results progressively and studies are being performed to advance our current understanding of the disease. It is well known that tumor necrosis factor (TNF) exerts a central role, along with interleukin-17 (IL-17) and interleukin-23 (IL-23), demonstrated by several clinical studies. Similar to other rheumatic inflammatory conditions, SA is associated with an early process of systemic bone loss, both trabecular and cortical, consecutive osteopenia, osteoporosis, and high fracture risk. Current personalized therapeutic options benefit from new published data, to prevent future complications and to improve quality of life. Contents 1. Introduction 2. Immunopathogenesis of ankylosing spondylitis 3. Effects of IL-23 and IL-17 on the bone 4. Conclusions

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Anti-IL17A in Axial Spondyloarthritis—Where Are We At?

Cited by 23 publications

References 47 publications

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

Nonradiographic axial spondyloarthritis: clinical and therapeutic relevance

New insights into IL‑17/IL‑23 signaling in ankylosing spondylitis (Review)

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