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F1000Research 2018The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing... (Review)
Review
The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease.
Topics: Disease Management; Humans; Spondylitis, Ankylosing; Therapeutics
PubMed: 30345001
DOI: 10.12688/f1000research.14956.1 -
Frontiers in Immunology 2019
Topics: Disease Management; Disease Susceptibility; Humans; Immune System Diseases; Spondylitis, Ankylosing
PubMed: 31214188
DOI: 10.3389/fimmu.2019.01232 -
Rheumatic Diseases Clinics of North... Aug 2017Ankylosing spondylitis (AS) is a common inflammatory arthritis in which genetic factors are the primary determinants of disease risk and severity. Substantial progress... (Review)
Review
Ankylosing spondylitis (AS) is a common inflammatory arthritis in which genetic factors are the primary determinants of disease risk and severity. Substantial progress has been made in identifying genetic pathways involved in the disease, and in translating those discoveries to drug discovery programs. Recently discovered novel disease pathways include those involved in control of DNA methylation, bacterial sensing, and mucosal immunity. Additional pathways are likely to be identified as a higher proportion of the genetic risk of AS is determined.
Topics: Genetic Pleiotropy; Genetic Predisposition to Disease; HLA-B27 Antigen; Humans; Spondylitis, Ankylosing
PubMed: 28711142
DOI: 10.1016/j.rdc.2017.04.006 -
Frontiers in Immunology 2021
Topics: Adaptive Immunity; Animals; Anti-Inflammatory Agents; Cost of Illness; Humans; Immunity, Innate; Quality of Life; Sacroiliac Joint; Spine; Spondylitis, Ankylosing
PubMed: 35003143
DOI: 10.3389/fimmu.2021.822582 -
Arthritis Care & Research Oct 2019To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). (Review)
Review
2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.
OBJECTIVE
To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).
METHODS
We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel.
RESULTS
Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended.
CONCLUSION
These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.
Topics: Antirheumatic Agents; Biomedical Research; Clinical Trials as Topic; Humans; Rheumatology; Spondylarthritis; Spondylitis, Ankylosing; Treatment Outcome; United States
PubMed: 31436026
DOI: 10.1002/acr.24025 -
Clinical Rheumatology Aug 2021Radiographic axial spondyloarthritis (also known as ankylosing spondylitis [AS]) is a chronic immune-mediated arthritis characterized by inflammation of the axial...
Radiographic axial spondyloarthritis (also known as ankylosing spondylitis [AS]) is a chronic immune-mediated arthritis characterized by inflammation of the axial skeleton, peripheral joints, and entheses. It is estimated that 1 in every 200 people are affected by AS, making it an important healthcare and socioeconomic issue. In this review, we aim to explore the current understanding of AS risk factors and provide a comprehensive update. Multiple search strings were used to identify articles of interest published in PubMed between January 1, 2013, and February 1, 2021. On the basis of the literature review and analysis, we present up-to-date information on the risk factors of developing AS and our viewpoints on disease onset and progression. Multiple genetic and nongenetic risk factors have been suggested in the onset of AS. HLA-B27 is known to have a strong association with the disease, but other genes have been implicated in disease development. Aside from genetics, other factors are thought to be involved; up to 70% of patients with AS have subclinical intestinal inflammation, suggesting that the origin of the disease may be in the gut. The exact mechanism by which AS onset begins is most likely complex and multifactorial. Key Points • It remains unclear how interactions between genes, microbes, mechanical stress, gender, and other environmental and lifestyle factors predispose patients to the development of ankylosing spondylitis (AS). • The exact mechanisms of AS are complex and multifactorial which will require much future research • Recognizing the risk factors, as well as understanding gene-environment interactions, may offer valuable insights into the etiology of AS and have important implications for diagnosis and treatment strategies.
Topics: HLA-B27 Antigen; Humans; Inflammation; Risk Factors; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 33754220
DOI: 10.1007/s10067-021-05679-7 -
Molecular Medicine Reports Apr 2017The study of ankylosing spondylitis (AS) has made significant progress over the last decade. Genome-wide association studies have identified and further substantiated... (Review)
Review
The study of ankylosing spondylitis (AS) has made significant progress over the last decade. Genome-wide association studies have identified and further substantiated the role of susceptibility genes outside the major histocompatibility complex locus. However, human leukocyte antigen (HLA)‑B27 has been suggested to be important in the pathogenesis of AS, contributing to ~20.1% of AS heritability. The current review will present the classical and non‑classical forms of HLA-B27, as well as their pathogenic roles, and further discuss the hypotheses regarding the potential pathogenesis of AS. In addition, the association between the pathogenic role of HLA‑B27 and inflammatory indexes, including the interleukin-23/‑17 axis will be investigated to provide novel insights into the pathogenesis of AS. The aim of the present review is to provide an update of the current research into the pathogenesis of AS, and provide a comprehensive description of the pathogenic role of HLA-B27 in AS.
Topics: Animals; HLA-B27 Antigen; Humans; Protein Folding; Protein Multimerization; Proteostasis Deficiencies; Spondylitis, Ankylosing
PubMed: 28259985
DOI: 10.3892/mmr.2017.6248 -
Annals of the Rheumatic Diseases Nov 2022To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs).
METHODS
Adults with active AS who met modified New York criteria and had an IR to one or two bDMARDs (tumour necrosis factor or interleukin-17 inhibitors) were randomised 1:1 to oral upadacitinib 15 mg once daily or placebo. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Sequentially tested secondary endpoints included Ankylosing Spondylitis Disease Activity score, Spondyloarthritis Research Consortium of Canada MRI spine inflammation score, total back pain, nocturnal back pain, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and Maastricht Ankylosing Spondylitis Enthesitis Score. Results are reported from the 14-week double-blind treatment period.
RESULTS
A total of 420 patients with active AS were randomised (upadacitinib 15 mg, n=211; placebo, n=209). Significantly more patients achieved the primary endpoint of ASAS40 at week 14 with upadacitinib vs placebo (45% vs 18%; p<0.0001). Statistically significant improvements were observed with upadacitinib vs placebo for all multiplicity-controlled secondary endpoints (p<0.0001). Adverse events were reported for 41% of upadacitinib-treated and 37% of placebo-treated patients through week 14. No events of malignancy, major adverse cardiovascular events, venous thromboembolism or deaths were reported with upadacitinib.
CONCLUSION
Upadacitinib 15 mg was significantly more effective than placebo over 14 weeks of treatment in bDMARD-IR patients with active AS. No new safety risks were identified with upadacitinib.
TRIAL REGISTRATION NUMBER
NCT04169373.
Topics: Adult; Antirheumatic Agents; Biological Therapy; Double-Blind Method; Heterocyclic Compounds, 3-Ring; Humans; Interleukin-17; Janus Kinase Inhibitors; Spondylarthritis; Spondylitis, Ankylosing; Treatment Outcome; Tumor Necrosis Factors
PubMed: 35788492
DOI: 10.1136/ard-2022-222608 -
Clinical and Experimental Rheumatology 2018Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammatory back pain and several other disease manifestations and comorbidities. The... (Review)
Review
Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammatory back pain and several other disease manifestations and comorbidities. The 2009 ASAS classification criteria differentiate between the classical ankylosing spondylitis or radiographic axSpA and non-radiographic axSpA based on the presence or absence of definite radiographic changes in the sacroiliac joints. Importantly, back pain in patients with axSpA may well have reasons other than axial inflammation or new bone formation. There are several important differential diagnoses such as diffuse idiopathic skeletal hyperostosis and osteitis condensans. This review summarises recent publications concerning the performance of imaging modalities in the field, such as conventional radiography, magnetic resonance imaging, computed tomography and dual energy x-ray absorptiometry including the trabecular bone score.
Topics: Back Pain; Diagnosis, Differential; Diagnostic Imaging; Humans; Predictive Value of Tests; Prognosis; Reproducibility of Results; Rheumatology; Sacroiliac Joint; Severity of Illness Index; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 30296971
DOI: No ID Found -
Rheumatology (Oxford, England) Oct 2020In recent years, significant progress has been made in improving the early diagnosis of spondyloarthritides (SpA), including axial SpA. Nonetheless, there are still... (Review)
Review
In recent years, significant progress has been made in improving the early diagnosis of spondyloarthritides (SpA), including axial SpA. Nonetheless, there are still issues related to the application of classification criteria for making the primary diagnosis of SpA in the daily practice. There are substantial conceptional and operational differences between the diagnostic vs classification approach. Although it is not possible to develop true diagnostic criteria for natural reasons as discussed in this review, the main principles of the diagnostic approach can be clearly defined: consider the pre-test probability of the disease, evaluate positive and negative results of the diagnostic test, exclude other entities, and estimate the probability of the disease at the end. Classification criteria should only be applied to patients with an established diagnosis and aimed at the identification of a rather homogeneous group of patients for the conduction of clinical research.
Topics: Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Spondylarthritis; Spondylitis, Ankylosing; Tomography, X-Ray Computed
PubMed: 33053191
DOI: 10.1093/rheumatology/keaa250