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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 -
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 -
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 -
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 -
Rheumatology (Oxford, England) Mar 2019In ankylosing spondylitis (AS), structural damage that occurs as a result of syndesmophyte formation and ankylosis of the vertebral column is irreversible. Structural... (Review)
Review
In ankylosing spondylitis (AS), structural damage that occurs as a result of syndesmophyte formation and ankylosis of the vertebral column is irreversible. Structural damage is currently assessed by conventional radiography and scoring systems that reliably assess radiographic structural damage are needed to capture the differential effects of drugs on structural damage progression. The validity of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) as a primary outcome measure in evaluating the effect of AS treatments on radiographic progression rates was assessed in this review. The mSASSS has not been used, to date, as a primary outcome measure in a prospective randomized controlled clinical trial of biologic therapy in AS. This review of the medical literature confirmed that the mSASSS is the most validated and widely used method for assessing radiographic progression in AS, correlating with worsening measures of disease signs and symptoms, spinal mobility and physical function, with a 2-year interval being required to ensure sufficient sensitivity to change.
Topics: Anti-Inflammatory Agents; Disease Progression; Humans; Radiography; Severity of Illness Index; Spondylitis, Ankylosing
PubMed: 29860356
DOI: 10.1093/rheumatology/key128 -
Revista Brasileira de Reumatologia 2017The purpose was to evaluate the effectiveness of a progressive muscle strengthening program using a Swiss ball for AS patients. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The purpose was to evaluate the effectiveness of a progressive muscle strengthening program using a Swiss ball for AS patients.
METHODS
Sixty patients with AS were randomized into the intervention group (IG) or the control group (CG). Eight exercises were performed by the IG patients with free weights on a Swiss ball two times per week for 16 weeks. The evaluations were performed by a blinded evaluator at baseline and after 4, 8, 12 and 16 weeks using the following instruments: the one-repetition maximum test (1 RM), BASMI, BASFI, HAQ-S, SF-36, 6-minute walk test, time up and go test, BASDAI, ASDAS, ESR and CRP dosage and Likert scale.
RESULTS
There was a statistical difference between groups for: strength (1 RM capacity) in the following exercises: abdominal, rowing, squat, triceps and reverse fly (p<0.005); 6-minute walk test (p<0.001); timed up and go test (p=0.025) and Likert scale (p<0.001), all of them with better results for the IG. No differences were observed between the groups with respect to the functional capacity evaluation using the BASFI, HAQ-S, BASMI, SF-36, TUG, ASDAS, ESR and CPR dosage.
CONCLUSIONS
Progressive muscle strengthening using a Swiss ball is effective for improving muscle strength and walking performance in patients with AS.
Topics: Adult; Exercise Therapy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscle Strength; Postural Balance; Spondylitis, Ankylosing; Sports Equipment; Treatment Outcome; Walking; Young Adult
PubMed: 28137402
DOI: 10.1016/j.rbre.2016.09.009 -
Frontiers in Immunology 2023Ankylosing Spondylitis (AS) is an inflammatory condition affecting the spine, which may lead to complications such as osteoporosis (OP). Many observational studies have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ankylosing Spondylitis (AS) is an inflammatory condition affecting the spine, which may lead to complications such as osteoporosis (OP). Many observational studies have demonstrated a close relationship with strong evidence between OP and AS. The combination of AS and OP is already an indisputable fact, but the exact mechanism of AS complicated with OP is unclear. To better prevent and treat OP in patients with AS, it is necessary to understand the specific mechanism of OP in these patients. In addition, there is a study showing that OP is a risk factor for AS, but the causal relationship between them is not yet clear. Therefore, we conducted a bidirectional Mendelian randomization (MR) analysis to determine whether there is a direct causal effect between AS and OP and to investigate the co-inherited genetic information between the two.
METHODS
Bone mineral density (BMD) was used as a phenotype for OP. The AS dataset was taken from the IGAS consortium and included people of European ancestry (9,069 cases and 13,578 controls). BMD datasets were obtained from the GEFOS consortium, a large GWAS meta-analysis study, and the UK Biobank and were categorized based on site (total body (TB): 56,284 cases; lumbar spine (LS): 28,498 cases; femoral neck (FN): 32,735 cases; forearm (FA): 8,143 cases; and heel: 265,627 cases) and age (0-15: 11,807 cases; 15-30: 4,180 cases; 30-45: 10,062 cases; 45-60: 18,062 cases; and over 60: 22,504 cases).To obtain the casual estimates, the inverse variant weighted (IVW) method was mainly used due to its good statistical power and robustness. The presence of heterogeneity was evaluated using Cochran's Q test. Pleiotropy was assessed utilizing MR-Egger regression and MR-pleiotropy residual sum and outlier (MR-PRESSO).
RESULTS
Generally, there were no significant causal associations between genetically predicted AS and decreased BMD levels. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. However, there was a sign of a connection between genetically elevated BMD levels and a decreased risk of AS (Heel-BMD: OR = 0.879, 95% CI: 0.795-0.971, = 0.012; Total-BMD: OR = 0.948, 95% CI: 0.907-0.990, = 0.017; LS-BMD: OR = 0.919, 95% CI: 0.861-0.980, = 0.010). The results were confirmed to be reliable by sensitivity analysis.
CONCLUSION
This MR study found that the causal association between genetic liability to AS and the risk of OP or lower BMD in the European population was not evident, which highlights the second effect (e.g., mechanical reasons such as limited movement) of AS on OP. However, genetically predicted decreased BMD/OP is a risk factor for AS with a causal relationship, implying that patients with OP should be aware of the potential risk of developing AS. Moreover, OP and AS share similar pathogenesis and pathways.
Topics: Humans; Spondylitis, Ankylosing; Mendelian Randomization Analysis; Osteoporosis; Causality; Lumbar Vertebrae
PubMed: 37359532
DOI: 10.3389/fimmu.2023.1163258 -
RMD Open Jul 2022Long-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported. (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Long-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported.
METHODS
In SELECT-AXIS 1, patients receiving placebo were switched to upadacitinib 15 mg once daily at week 14 while patients initially randomised to upadacitinib continued their regimen through week 104. Efficacy was assessed using as-observed (AO) and non-responder imputation (NRI).
RESULTS
Of 187 patients randomised, 144 patients (77%) completed week 104. Among patients receiving continuous upadacitinib, 85.9% (AO) and 65.6% (NRI) achieved Assessment of SpondyloArthritis international Society 40 response (ASAS40) at week 104. Similar magnitude of ASAS40 responses were observed among patients who switched from placebo to upadacitinib (88.7% and 63.8%, respectively). The mean change from baseline to week 104 in Spondyloarthritis Research Consortium of Canada MRI spine and sacroiliac joint inflammation scores were -7.3 and -5.3, respectively, in the continuous upadacitinib group and -7.9 and -4.9 in the placebo-to-upadacitinib switch group. The mean (95% CI) change from baseline to week 104 in the modified Stoke Ankylosing Spondylitis Spine Score was 0.7 (0.3, 1.1) in the total group. Adverse event rate was 242.7/100 patient-years. No serious infections, adjudicated major adverse cardiovascular events, lymphoma, non-melanoma skin cancer, or gastrointestinal perforations were observed.
CONCLUSIONS
Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 2 years for ASAS40 and other clinically relevant endpoints. A low rate of radiographic progression was observed and no new safety findings were observed.
Topics: Antirheumatic Agents; Heterocyclic Compounds, 3-Ring; Humans; Spondylarthritis; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 35896281
DOI: 10.1136/rmdopen-2022-002280