Systemic effects of IL-17 in inflammatory arthritis

Beringer, Audrey; Miossec, Pierre

doi:10.1038/s41584-019-0243-5

Cited by 97 publications

(92 citation statements)

References 124 publications

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“…In addition, IL-1β, IL-6, IL-21, and IL-23 support the differentiation of T helper 17 (Th17) cells, suppress the differentiation of regulatory T cells, and cause inflammation of arthritis [ 9 ]. IL-17 has powerful properties in inducing neutrophil-attracting chemokines to initiate and promote inflammation and helps to destroy cartilage and increase osteoclast differentiation, leading to bone erosion in joints [ 9 , 34 , 35 ]. Moreover, the sustained activation of the IL-17 axis leads to an accumulation of immune cells in the synovium and increased intercellular interactions, thereby forming a pro-inflammatory environment that could in turn promote the synergistic collaboration of IL-17 with TNF-α, IL-1β, IL-18, and many other cytokines [ 35 ].…”

Section: Key Molecules Implicated In the Pathogenesis Of Arthritismentioning

confidence: 99%

A20: a master regulator of arthritis

Huang

et al. 2020

Arthritis Res Ther

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A20, also known as TNF-α-induced protein 3 (TNFAIP3), is an anti-inflammatory protein that plays an important part in both immune responses and cell death. Impaired A20 function is associated with several human inflammatory and autoimmune diseases. Although the role of A20 in mediating inflammation has been frequently discussed, its intrinsic link to arthritis awaits further explanation. Here, we review new findings that further demonstrate the molecular mechanisms through which A20 regulates inflammatory arthritis, and we discuss the regulation of A20 by many factors. We conclude by reviewing the latest A20-associated mouse models that have been applied in related research because they reflect the characteristics of arthritis, the study of which will hopefully cast new light on anti-arthritis treatments.

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Section: Key Molecules Implicated In the Pathogenesis Of Arthritismentioning

confidence: 99%

A20: a master regulator of arthritis

Huang

et al. 2020

Arthritis Res Ther

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“…This activity indicates that IL-17 blockade is a potential and efficient treatment option. During the past decade, there has been an increasing interest in the use of IL-17 inhibitors (such as secukinumab, ixekizumab, and brodalumab) in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis [11].…”

Section: Doimentioning

confidence: 99%

Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis

Yin

Wang

Liu

et al. 2020

Preprint

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Objectives: To systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis. Methods: A systematic review of the literature was performed for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. Meta-analyses were used to determine the efficacy and safety of the IL-17 inhibitors in the treatment of these patients. The primary end point was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary end point was defined as ASAS40 at week 16. Results: Six phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR=1.63, 95% CI 1.45 to 1.84, p=0.00) and the secondary endpoint ASAS40 response rate (RR=2.12, 95% CI 1.75 to 2.56, p=0.00) versus those for the placebo. With respect to the safety profile, more treatment-emergent adverse events (RR=1.11, 95% CI 1.01 to 1.22, p=0.03) and non-severe infections (RR=1.82, 95% CI 1.40 to 2.37, p<0.001) were described after treatment with IL-17 inhibitors than after treatment with placebo, while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including death, discontinuation due to adverse events, or serious adverse events. Conclusions: IL-17 inhibitors produced favourable response rates but an increased risk of non-severe infections in the treatment of active ankylosing spondylitis.

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“…During the past decade, there has been an increasing interest in the use of IL-17 inhibitors (such as secukinumab, ixekizumab, and brodalumab) in the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. 12 Secukinumab is a fully recombinant human immunoglobulin G (IgG)1 kappa monoclonal antibody (mAb) that directly inhibits IL-17A. It is the first approved IL-17 inhibitor for the treatment of patients with ankylosing spondylitis.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a meta-analysis of randomized controlled trials

Yin

Wang

Liu

et al. 2020

Preprint

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Objectives: To systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis.Methods: Electronic databases were searched for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. The efficacy and safety of the IL-17 inhibitors in the treatment of these patients were compared to those of a placebo. The primary end point was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary end point was defined as ASAS40 at week 16.Results: Six phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR=1.63, 95% CI 1.45 to 1.84, p=0.00) and the secondary endpoint ASAS40 response rate (RR=2.12, 95% CI 1.75 to 2.56, p=0.00) versus those for the placebo. With respect to the safety profile, more infectious diseases were described after treatment with IL-17 inhibitors than after treatment with placebo (RR=1.82, 95% CI 1.40 to 2.37, p<0.001), while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including treatment-emergent adverse events, death, discontinuation due to adverse event, serious adverse events, or total adverse events.Conclusions: IL-17 inhibitors produced favourable response rates but an increased risk of infectious diseases in the treatment of active ankylosing spondylitis.

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Systemic effects of IL-17 in inflammatory arthritis

Cited by 97 publications

References 124 publications

A20: a master regulator of arthritis

A20: a master regulator of arthritis

Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis

Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a meta-analysis of randomized controlled trials

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