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Frontiers in Immunology 2019
Topics: Disease Management; Disease Susceptibility; Humans; Immune System Diseases; Spondylitis, Ankylosing
PubMed: 31214188
DOI: 10.3389/fimmu.2019.01232 -
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 -
Frontiers in Immunology 2021The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked... (Review)
Review
The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked to psoriasis and also the arthritis associated with inflammatory bowel disease. The argument supporting the role for IL-23 across the spectrum of SpA comes from 4 sources. First, genome wide associated studies (GWAS) have shown that all the aforementioned disorders exhibit IL-23R pathway SNPs, whereas HLA-B27 is not linked to all of these diseases-hence the IL-23 pathway represents the common genetic denominator. Secondly, experimental animal models have demonstrated a pivotal role for the IL-23/IL-17 axis in SpA related arthropathy that initially manifests as enthesitis, but also synovitis and axial inflammation and also associated aortic root and cutaneous inflammation. Thirdly, the emergent immunology of the human enthesis also supports the presence of IL-23 producing myeloid cells, not just at the enthesis but in other SpA associated sites including skin and gut. Finally, drugs that target the IL-23 pathway show excellent efficacy for skin disease, efficacy for IBD and also in peripheral arthropathy associated with SpA. The apparent failure of IL-23 blockade in the AS which is effectively a spinal polyenthesitis but evidence for efficacy of IL-23 inhibition for peripheral enthesitis in PsA and preliminary suggestions for benefit in axial PsA, raises many questions. Key amongst these is whether spinal inflammation may exhibit entheseal IL-17A production independent of IL-23 but peripheral enthesitis is largely dependent on IL-23 driven IL-17 production. Furthermore, IL-23 blocking strategies in animal models may prevent experimental SpA evolution but not prevent established disease, perhaps pointing towards a role for IL-23 in innate immune disease initiation whereas persistent disease is dependent on memory T-cell responses that drive IL-17A production independently of IL-23, but this needs further study. Furthermore, IL-12/23 posology in inflammatory bowel disease is substantially higher than that used in AS trials which merits consideration. Therefore, the IL-23 pathway is centrally involved in the SpA concept but the nuances and intricacies in axial inflammation that suggest non-response to IL-23 antagonism await formal definition. The absence of comparative immunology between the different skeletal sites renders explanations purely hypothetical at this juncture.
Topics: Animals; Biomarkers; Diagnosis, Differential; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Interleukin-17; Interleukin-23; Molecular Targeted Therapy; Signal Transduction; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 33815371
DOI: 10.3389/fimmu.2021.614255 -
Annals of the Rheumatic Diseases Apr 2023Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic...
OBJECTIVES
Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum.
METHODS
In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24.
RESULTS
254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low.
CONCLUSIONS
Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.
Topics: Humans; Interleukin-17; Non-Radiographic Axial Spondyloarthritis; Treatment Outcome; Spondylitis, Ankylosing; Spondylarthritis; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 36649967
DOI: 10.1136/ard-2022-223595 -
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 -
Clinical and Experimental Rheumatology Nov 2023Axial spondyloarthritides (axSpA) are a group of systemic autoimmune diseases, characterised by an inflammatory involvement of the axial skeleton, which, in the earlier... (Review)
Review
Axial spondyloarthritides (axSpA) are a group of systemic autoimmune diseases, characterised by an inflammatory involvement of the axial skeleton, which, in the earlier phases, cannot be detected by conventional radiology, but only by magnetic resonance imaging, thus defining the so-called non-radiographic axSpA (nr-axSpA). The initial osteitis then tends to complicate into bone reabsorption and aberrant bone deposition, which then determines the ankylosis of the axial skeleton in the latest phases of the disease.Peripheral joints may also be affected, enthesitis being its more characteristic manifestation. The radiographic form corresponds to ankylosing spondylitis which, with psoriatic arthritis, is the best-known subtype of SpA. AxSpA are rarely associated to laboratory abnormalities and are usually complicated by the presence of both extra-articular manifestations (particularly acute anterior uveitis, psoriasis and inflamatory bowel disease) and comorbidities, with a subsequent higher risk for patients of an impaired quality of life.In this paper we reviewed the literature on axSpA of 2021 and 2022 (Medline search of articles published from 1st January 2021 to 31st December 2022).
Topics: Humans; Spondylarthritis; Quality of Life; Spondylitis, Ankylosing; Arthritis, Psoriatic; Psoriasis
PubMed: 37965699
DOI: 10.55563/clinexprheumatol/9fhz98 -
Frontiers in Immunology 2021Genetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies...
OBJECTIVE
Genetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot.
METHODS
We integrated single-cell assaying transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to explore the key genes and related mechanisms associated with AS pathogenesis.
RESULTS
We identified 18 cell types in peripheral mononuclear cells from patients with AS and normal controls and summarized the cell-type-specific abnormal genes by scRNA-seq. Interestingly, we found that the pathogenic gene involved in AS progression originated from CD8+ T cells. Moreover, we observed an abnormal tumor TNF pathway mediated by abnormal expression of , , , , and , and scATAC-seq results confirmed the abnormal accessible binding sites of transcriptional factors , , and . The final magnetic bead sorting and quantitative real-time PCR(RT-qPCR) confirmed that , , , and in CD8+ T cells differed in the AS group.
CONCLUSIONS
Our results revealed a possible mechanism by which abnormally regulates , , and and drives progression, providing a novel perspective from a single cell point of view in AS.
Topics: Adult; Chromatin Immunoprecipitation Sequencing; Female; Gene Expression; Humans; Leukocytes, Mononuclear; Male; RNA-Seq; Single-Cell Analysis; Spondylitis, Ankylosing; Transcription Factors; Young Adult
PubMed: 34880858
DOI: 10.3389/fimmu.2021.760381 -
Acta Reumatologica Portuguesa 2021Ankylosing spondylitis (AS) reduces spinal mobility, which results in structural and functional impairments. Pulmonary problems eventually occur in most AS patients due... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Ankylosing spondylitis (AS) reduces spinal mobility, which results in structural and functional impairments. Pulmonary problems eventually occur in most AS patients due to interstitial lung disease or as a result of chest wall abnormalities. The aim of this study was to evaluate the effects on pulmonary functions and disease related scales of aquatic and land-based multidimensional functional mobility exercises on pulmonary functions in patients with AS.
METHODS
In this randomized controlled study, 57 patients with definite AS according to the modified New York criteria were randomly allocated to an aquatic (AG), land-based (LG), or home (HG) exercise group and performed multidimensional mobility exercise sessions twice a week for 8 weeks. The Bath indices were used to measure disease activity, functional limitation, and spinal mobility, and a 10-cm visual analog scale assessed pain during activity and at rest. Pulmonary function tests, maximal inspiratory mouth pressure (MIP), and maximal expiratory mouth pressure (MEP) were measured before and after the intervention. The study is registered at ClinicalTrials.gov, number NCT03667625 (27/08/2018).
RESULTS
Forty-six patients (30.4% female) with a mean age of 42.0 years completed the study. Multidimensional exercises improved disease-related symptoms such as pain, spinal mobility, and functionality, but there were no significant changes in HG. Patients in AG showed significant improvements in peak expiratory flow (p=0.004), vital capacity (p=0.025), maximum voluntary ventilation (p=0.006), and MIP (p=0.001), while those in LG showed significant increases in forced expiratory volume during the first second to forced vital capacity (FEV1/FVC) ratio (p=0.049), peak expiratory flow (p=0.007), and maximum voluntary ventilation (p=0.004). There were no significant changes in HG.
CONCLUSIONS
Multidimensional functional mobility exercises performed either in water or on land are important in the management of pulmonary manifestations of AS.
Topics: Adult; Exercise; Exercise Therapy; Female; Humans; Male; Spine; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 34962245
DOI: No ID Found -
Frontiers in Immunology 2023The relationship between ankylosing spondylitis (AS) and glaucoma in the European population remains unclear. In the present study, we applied a two-sample Mendelian...
BACKGROUND
The relationship between ankylosing spondylitis (AS) and glaucoma in the European population remains unclear. In the present study, we applied a two-sample Mendelian randomization (MR) method to investigate their causal relationship.
METHODS
MR analysis was conducted to validate the causal associations between AS with glaucoma using summary statistics from the genome-wide association studies of AS (9,069 cases and 13,578 control subjects) and glaucoma (8,591 cases and 210,201 control subjects). The inverse variance weighting method was performed to evaluate the causal relationship. The MR-Egger regression approach was applied to assess pleiotropy, while Cochran's Q test was used to analyze heterogeneity. Subgroup analysis was performed according to primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).
RESULTS
The results of the MR study reveal a risk-increasing causal relationship between AS and glaucoma among European populations (OR = 1.35, 95%CI = 1.16-1.57, = 8.81 × 10). Pleiotropy and heterogeneity were not found in our study. In the subgroup analysis, AS was also causal with POAG (OR = 1.48, 95%CI = 1.17-1.86, P = 8.80 × 10) and PACG (OR = 1.91, 95%CI = 1.03-3.51, P = 3.88 × 10).
CONCLUSION
The results of the MR analysis suggested a causal relationship between AS and glaucoma in the European population. Further studies are needed to identify the specific mechanism between these two diseases.
Topics: Humans; Spondylitis, Ankylosing; Genome-Wide Association Study; Glaucoma, Open-Angle; Mendelian Randomization Analysis; Glaucoma
PubMed: 37020551
DOI: 10.3389/fimmu.2023.1120742 -
Pharmacology 2022Janus kinase (JAK) inhibitors and secukinumab have been demonstrated to be effective treatments for ankylosing spondylitis (AS). However, there have been no head-to-head... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Janus kinase (JAK) inhibitors and secukinumab have been demonstrated to be effective treatments for ankylosing spondylitis (AS). However, there have been no head-to-head trials comparing the effectiveness and safety characteristics of JAK inhibitors with secukinumab. This study aimed to evaluate the relative effectiveness and safety of JAK inhibitors and secukinumab in patients with active AS.
SUMMARY
A Bayesian network meta-analysis was conducted using direct and indirect data from randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib 5 mg, upadacitinib 15 mg, filgotinib 200 mg, and secukinumab 150 mg in patients with active AS who had a poor response or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs) and were tumor necrosis factor (TNF) inhibitor-naïve. Data from six RCTs comprising 937 patients were analyzed. The Assessment of SpondyloArthritis International Society 20 (ASAS20) response rates were significantly higher in the JAK inhibitors and secukinumab groups than in the placebo group. The surface under the cumulative ranking curve (SUCRA)-based ranking probability based on the ASAS20 response rate suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS20 response rate, followed by filgotinib 200 mg, upadacitinib 15 mg, secukinumab 150 mg, and placebo. The SUCRA-based ranking probability based on the ASAS20 response rate suggested that tofacitinib 5 mg had the highest likelihood of being the best treatment for achieving the ASAS40 response rate, followed by upadacitinib 15 mg, secukinumab 150 mg, filgotinib 200 mg, and placebo.
KEY MESSAGES
Tofacitinib 5 mg was the most effective treatment for AS, whereas JAK inhibitors and secukinumab 150 mg were effective treatments in patients with active AS who had a poor response or intolerance to NSAIDs and were TNF inhibitor-naïve.
Topics: Humans; Janus Kinase Inhibitors; Spondylitis, Ankylosing; Antirheumatic Agents; Treatment Outcome; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 35817017
DOI: 10.1159/000525627