| Title |
Beyond the TNF-α Inhibitors: New and Emerging Targeted Therapies for Patients with Axial Spondyloarthritis and their Relation to Pathophysiology
|
|---|---|
| Published in |
Drugs, August 2018
|
| DOI | 10.1007/s40265-018-0971-x |
| Pubmed ID | |
| Authors |
Susanne Juhl Pedersen, Walter P. Maksymowych |
| Abstract |
Axial spondyloarthritis (axSpA) is a complex disease that affects the joints and entheses of axial and peripheral joints, and is associated with inflammation in extra-articular sites such as the gut. Improved knowledge on genetics and immunology has improved treatment options with the availability of treatments targeting tumor necrosis factor-α (TNF-α) and interleukin (IL)-17. However, these agents do not provide clinical benefit for about 40% of patients, and additional therapeutic options are necessary. Theories on pathogenesis includes misfolding of HLA-B*27 during its assembly leading to endoplasmic reticulum stress and autophagy/unfolded protein response (UPR). HLA-B*27 may express free heavy chain on the cell surface, which activates innate immune receptors on T, natural killer, and myeloid cells with pro-inflammatory effects. Activation of UPR genes is associated with increased TNF-α, interleukin-23 (IL-23), IL-17, interferon-γ expression, and expansion of T helper (Th)-17 cells. Certain genotypes of endoplasmic reticulum aminopeptidase (ERAP) 1 and 2 are associated with ankylosing spondylitis (AS) and functionally interact with the HLA-B27 peptidome. Innate immune cells type 3, which express RORγt, regulate expression of IL-17 and IL-22 in T cells. Stimulation of gamma-delta T cells with IL-23 also induces IL-17. Mucosa-associated invariant T cells residing in the gut mucosa express IL-17 in AS patients after stimulation with IL-7. Prostaglandin E2 induces IL-17A independent of IL-23 via IL-1β and IL-6. The pathogenic role of gut inflammation, zonulin and microbiota, which has a different composition in AS patients, remains to be elucidated. This article also includes a comprehensive review on the mechanism of action and efficacy of the biological treatments currently approved for axSpA (TNF-α inhibitors and IL-17 inhibitors) and future targets for treatment (other IL-17 family member (s), Janus kinase, IL-23, and phosphodiesterase 4). |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 14% |
| Unknown | 6 | 86% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 7 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 64 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 64 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 16% |
| Student > Master | 8 | 13% |
| Student > Ph. D. Student | 5 | 8% |
| Other | 5 | 8% |
| Student > Bachelor | 4 | 6% |
| Other | 9 | 14% |
| Unknown | 23 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 18 | 28% |
| Biochemistry, Genetics and Molecular Biology | 5 | 8% |
| Immunology and Microbiology | 5 | 8% |
| Social Sciences | 3 | 5% |
| Agricultural and Biological Sciences | 2 | 3% |
| Other | 6 | 9% |
| Unknown | 25 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 July 2019.
All research outputs
#14,140,033
of 23,102,082 outputs
Outputs from Drugs
#2,654
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Outputs of similar age
#181,397
of 335,278 outputs
Outputs of similar age from Drugs
#22
of 30 outputs
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