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RMD Open Jun 2024The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and...
INTRODUCTION
The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed.
METHODS
Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment.
RESULTS
After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (β coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (β coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis.
CONCLUSION
Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.
Topics: Humans; Male; Female; Atherosclerosis; Middle Aged; Inflammation; Adult; Heart Disease Risk Factors; Sex Factors; Axial Spondyloarthritis; Risk Factors; Biomarkers; Cardiovascular Diseases; C-Reactive Protein
PubMed: 38942590
DOI: 10.1136/rmdopen-2024-004187 -
Archives of Physical Medicine and... Jun 2024This study aimed to assess the effectiveness of exercise therapy for Axial spondyloarthritis (axSpA) patients. (Review)
Review
OBJECTIVE
This study aimed to assess the effectiveness of exercise therapy for Axial spondyloarthritis (axSpA) patients.
DATA SOURCES
From the database inception to March 2024, we searched PubMed (via Medline), Cochrane Library, Embase, Web of Science, Scopus, and SPORTDiscus for all relevant publications without any language restriction.
STUDY SELECTION
We included randomized controlled trials (RCTs) for axSpA patients in which at least one group received exercise therapy.
DATA EXTRACTION
Two independent reviewers assessed the quality of the literature using the Cochrane Collaboration Risk of Bias Tool 2.0. The outcomes were ankylosing spondylitis (AS) disease activity score (ASDAS), Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI), 6-minute walk distance (6MWT), Chest expansion capacity, Peak oxygen consumption (VOpeak), pain, fatigue, C-reactive protein (CRP), and Eythrocyte sedimentation rate (ESR).
DATA SYNTHESIS
A total of 20 RCTs, including 1,670 patients, were included in this study. Compared with the control group, exercise therapy improved BASFI (weighted mean difference [WMD]: -0.49, 95% confidence interval [CI]: -0.65 to -0.32, I= 3.4%, P=0.414), BASMI (WMD: -0.49, 95% CI: -0.87 to -0.11, I= 71.9%, P=0.679), BASDAI (WMD: -0.78, 95% CI: -1.08, -0.47, I=55.9%, P=0.021), ASDAS (WMD: -0.44, 95% CI: -0.64 to -0.24, I =0.0%, P=0.424), VOpeak (WMD: 3.16, 95% CI: 1.37 to 4.94, I=0.0%, P=0.873), 6MWT (WMD: 27.64, 95% CI: 12.04 to 43.24, I= 0.0%, P=0.922), Pain (standardized mean difference [SMD]: -0.47, 95% CI: -0.74 to -0.21, I= 66.0%, P=0.046) and Fatigue (SMD: -0.49, 95% CI: -0.71 to -0.27, I= 0.0%, P=0.446). However, no significant benefit was found in Chest expansion, CRP, and ESR outcomes.
CONCLUSIONS
Exercise therapy is an effective strategy for improving disease control and symptom relief in axSpA.
PubMed: 38942347
DOI: 10.1016/j.apmr.2024.06.005 -
The Lancet. Rheumatology Jun 2024Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial...
Granulocyte-macrophage colony-stimulating factor neutralisation in patients with axial spondyloarthritis in the UK (NAMASTE): a randomised, double-blind, placebo-controlled, phase 2 trial.
BACKGROUND
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial spondyloarthritis. Namilumab is a human IgG1 monoclonal anti-GM-CSF antibody that potently neutralises human GM-CSF. We aimed to assess the efficacy of namilumab in participants with moderate-to-severe active axial spondyloarthritis.
METHODS
This proof-of-concept, randomised, double-blind, placebo-controlled, phase 2, Bayesian (NAMASTE) trial was done at nine hospitals in the UK. Participants aged 18-75 years with axial spondyloarthritis, meeting the Assessment in SpondyloArthritis international Society (ASAS) criteria and the ASAS-defined MRI criteria, with active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), were eligible. Those who had inadequately responded or had intolerance to previous treatment with an anti-TNF agent were included. Participants were randomly assigned (6:1) to receive subcutaneous namilumab 150 mg or placebo at weeks 0, 2, 6, and 10. Participants, site staff (except pharmacy staff), and central study staff were masked to treatment assignment. The primary endpoint was the proportion of participants who had an ASAS ≥20% improvement (ASAS20) clinical response at week 12 in the full analysis set (all randomly assigned participants). This trial is registered with ClinicalTrials.gov (NCT03622658).
FINDINGS
From Sept 6, 2018, to July 25, 2019, 60 patients with moderate-to-severe active axial spondyloarthritis were assessed for eligibility and 42 were randomly assigned to receive namilumab (n=36) or placebo (n=six). The mean age of participants was 39·5 years (SD 13·3), 17 were women, 25 were men, 39 were White, and seven had previously received anti-TNF therapy. The primary endpoint was not met. At week 12, the proportion of patients who had an ASAS20 clinical response was lower in the namilumab group (14 of 36) than in the placebo group (three of six; estimated between-group difference 6·8%). The Bayesian posterior probability η was 0·72 (>0·927 suggests high clinical significance). The rates of any treatment-emergent adverse events in the namilumab group were similar to those in the placebo group (31 vs five).
INTERPRETATION
Namilumab did not show efficacy compared with placebo in patients with active axial spondyloarthritis, but the treatment was generally well tolerated.
FUNDING
Izana Bioscience, NIHR Oxford Biomedical Research Centre (BRC), NIHR Birmingham BRC, and Clinical Research Facility.
PubMed: 38942047
DOI: 10.1016/S2665-9913(24)00099-7 -
Journal of Neurosurgery. Spine Jun 2024This study aimed to provide a method for determining the apical vertebra for pedicle subtraction osteotomy (PSO) in corrective surgery for patients with ankylosing...
OBJECTIVE
This study aimed to provide a method for determining the apical vertebra for pedicle subtraction osteotomy (PSO) in corrective surgery for patients with ankylosing spondylitis (AS) with thoracolumbar kyphosis (TLK).
METHODS
The medical records of AS patients with TLK who underwent PSO between May 2009 and August 2022 were retrospectively reviewed, and 235 patients were included in the study. Using the proposed method, choosing the vertebra based on Kim's apex (KA), which is defined as the farthest vertebra from a line drawn from the center of the T10 vertebral body to the midpoint of the S1 upper endplate, the authors analyzed 229 patients with apices at T12, L1, or L2 (excluding L3 because of the small sample size, n = 6). They divided all patients into two groups. Group A (n = 144) underwent PSO at the KA vertebra, while group B (n = 85) underwent PSO at a different level. Demographic and radiological data, including sagittal spinopelvic parameters of the entire spine, were collected. An additional analysis was performed on patients with the same KA vertebra.
RESULTS
The vertebra distributions of patients based on KA were T12 (28 [12.2%]), L1 (119 [52.0%]), and L2 (82 [35.8%]). The corrections of sagittal vertical axis (SVA; 101.0 ± 48.5 mm vs 82.0 ± 53.8 mm, p = 0.010), global kyphosis (GK; 31.6° ± 10.0° vs 26.4° ± 10.5°, p = 0.005), and TLK (29.4° ± 10.2° vs 24.2° ± 12.9°, p = 0.012) in group A were significantly greater than those in group B, and there was no difference in the corrections of thoracic kyphosis (TK), lumbar lordosis, and pelvic incidence between the two groups. On further analysis, group A showed greater correction in TK (26.2° ± 13.7° vs 0.1° ± 8.1°, p = 0.013) for patients with T12 as the KA; greater improvements in SVA (101.5 ± 44.2 mm vs 73.4 ± 48.7 mm, p = 0.020), GK (30.6° ± 11.0° vs 25.0° ± 10.4°, p = 0.046), and TLK (32.6° ± 7.8° vs 26.7° ± 9.9°, p = 0.012) for those with L1 as the KA; and significant correction in TLK (30.0° ± 6.3° vs 4.3° ± 19.5°, p = 0.008) for patients with L2 as the KA, compared with group B.
CONCLUSIONS
PSO at the apical vertebra provides a greater degree of correction of sagittal imbalance. The proposed method, selecting the vertebra based on KA, is easily reproducible for determining the apex level in AS patients with TLK.
PubMed: 38941634
DOI: 10.3171/2024.4.SPINE231218 -
Medicine Jun 2024Our aim is to evaluate serum Raftlin levels as a biomarker for diagnosing and monitoring disease activity in patients with axial spondyloarthritis (axSpA) and Psoriatic... (Observational Study)
Observational Study
Our aim is to evaluate serum Raftlin levels as a biomarker for diagnosing and monitoring disease activity in patients with axial spondyloarthritis (axSpA) and Psoriatic arthritis (PsA). This trial included 40 axSpA patients, 40 PsA patients, and 40 healthy participants as the control group. Disease activity was assessed with Ankylosing Spondylitis Disease Activity Score for axSpA patients and The Disease Activity Index for Psoriatic Arthritis for PsA patients. The Spondyloarthritis Research Consortium of Canada index, health assessment questionnaire-disability index, and numeric rating scale were used to evaluate the enthesitis severity, disability, and pain status of all patients. Serum Raftlin levels were determined using the ELISA method. The 3 groups had no statistical differences regarding gender, age, weight, height, BMI, educational status, and exercise habits. The axSpA group had higher Raftlin levels than the PsA and control groups, and Raftlin levels were statistically significant in predicting the likelihood of axSpA. We found no statistically significant differences between the PsA and control groups. We found no statistically significant difference in Raftlin levels in HLA-B27 positive versus HLA-B27 negative patients in both axSpA and PsA groups. Our results also did not detect any correlation of Raftlin levels with Ankylosing Spondylitis Disease Activity Score, C-reactive protein, erythrocyte sedimentation rate, health assessment questionnaire-disability index, numeric rating scale, and Spondyloarthritis Research Consortium of Canada index in axSpA patients. Receiver operating characteristic analysis determined that Raftlin level ≥ 6.31 ng/mL discriminates axSpA from normal individuals with 92.5% sensitivity, 59% specificity, and an area under the curve of 0.738. Our results demonstrate that although serum Raftlin levels are elevated in axSpA patients, Raftlin cannot be used as an alone diagnostic marker for axSpA. Furthermore, it was not found to be related to the monitoring of disease activity, the level of pain, disability, or severity of enthesitis. This study is prospectively registered at www.clinicaltrials.gov (ID: NCT05771389).
Topics: Humans; Male; Female; Biomarkers; Arthritis, Psoriatic; Adult; Axial Spondyloarthritis; Severity of Illness Index; Middle Aged; Membrane Proteins; Case-Control Studies
PubMed: 38941376
DOI: 10.1097/MD.0000000000038770 -
Cureus May 2024Hepatic tuberculosis (TB) is an uncommon extrapulmonary manifestation of tuberculosis. Hepatic TB is more common in immunocompromised patients, such as those on...
Hepatic tuberculosis (TB) is an uncommon extrapulmonary manifestation of tuberculosis. Hepatic TB is more common in immunocompromised patients, such as those on immunosuppressive medications or those with a human immunodeficiency virus (HIV) infection. Primary hepatic TB is rare, and liver involvement is often secondary to spreading from the lymphatics, portal vein, or hepatic artery. We report a case of hepatic TB in a patient on adalimumab for ankylosing spondylitis (AS).
PubMed: 38939259
DOI: 10.7759/cureus.61264 -
Archives of Rheumatology Jun 2024The study aimed to evaluate the role of ultrasonographic assessment of enthesitis in patients with spondyloarthritis (SpA) in terms of disease activity, functionality,...
OBJECTIVES
The study aimed to evaluate the role of ultrasonographic assessment of enthesitis in patients with spondyloarthritis (SpA) in terms of disease activity, functionality, and quality of life.
PATIENTS AND METHODS
Ninety SpA patients (57 males, 33 females; mean age: 37.5±9.7 years; range, 18 to 60 years) were included in cross-sectional study between November 2016 and January 2017. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), Short Form-12 (SF-12), and Ankylosing Spondylitis Quality of Life (ASQoL) were utilized for clinical evaluation. The clinical evaluation of enthesitis was performed with the Spondyloarthritis Research Consortium of Canada (SPARCC) and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) via an algometer calibrated to 4 kg/cm of pressure. Ultrasound evaluation was performed according to Madrid Sonographic Enthesitis Index (MASEI). A total of 2,610 entheseal sites were examined clinically, and 1,080 were assessed ultrasonographically.
RESULTS
A significant proportion of enthesitis (463/1,080) was detected on ultrasonographic evaluation but not with clinical enthesitis score (MASES and SPARCC). Although ultrasonographic entheseal evaluation detected enthesitis in at least one enthesis of all patients, 35 of the patients had no enthesitis with clinical examination. The sites most frequently involved in the entheses were the proximal patellar tendon and Achilles tendon. The MASEI score did not correlate with the MASES, SPARCC, BASDAI, SF-12, and ASQoL but moderately correlated with the C-reactive protein (CRP) level (r=0.348), ASDAS-CRP (r=0.294), and BASFI score (r=0.244).
CONCLUSION
The association of ultrasonography scores with CRP levels and ASDAS-CRP indicates that ultrasonography is effective in detecting inflammation. The MASEI score weakly correlates with functionality but not with quality of life. Ultrasonographic evaluation is invaluable and merits to be incorporated into SpA disease scoring system.
PubMed: 38933722
DOI: 10.46497/ArchRheumatol.2024.10224 -
Archives of Rheumatology Jun 2024This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS).
OBJECTIVES
This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS).
PATIENTS AND METHODS
A total of 811 AS patients registered in the TURKBIO registry database between 2011 and 2019 were categorized according to their age at the time of entry into the registry and assigned to one of two groups: young patients, defined as <60 years of age (n=610), and those aged ≥60 years (n=201) were recorded as elderly patients. Demographic, clinical, and laboratory characteristics, along with disease activity markers and other follow-up parameters, as well as current and prior treatments, were electronically recorded during each visit using open-source software.
RESULTS
The mean age of the elderly patients was 67±5.8 years, while the mean age of the younger patients was 49.2±10.9 years. Male predominance was lower in the older AS group compared to the younger AS group (p=0.002). During follow-up period, 397 patients (comprising 318 young and 79 elderly individuals) had a history of using at least one biological disease-modifying agent (bDMARD). There was no significant difference between the groups in terms of DMARD and bDMARD-use distributions. First tumor necrosis factor inhibitor (TNFi) retention rates were found to be similar in both groups over 10 years of follow-up. Adverse events were found to be similar in young (19.9%) and elderly (26.8%) AS patients.
CONCLUSION
Research in the TURKBIO cohort reveals that both older and younger patients with AS exhibited similar disease activity levels with comparable treatment approaches. Moreover, the results of TNFi treatments in elderly patients were the same as those observed in younger patients, with no notable increase in safety concerns.
PubMed: 38933720
DOI: 10.46497/ArchRheumatol.2024.10391 -
International Journal of Rheumatic... Jun 2024Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to...
OBJECTIVE
Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively.
METHODS
Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma.
RESULTS
Findings indicated that the treatment-induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post-treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity.
CONCLUSION
Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy.
Topics: Humans; Spondylitis, Ankylosing; Gastrointestinal Microbiome; Male; Antibodies, Monoclonal, Humanized; Female; Adult; Feces; Metabolomics; Treatment Outcome; RNA, Ribosomal, 16S; Case-Control Studies; Ribotyping; Middle Aged; Bacteria; Biomarkers; Predictive Value of Tests; Dysbiosis
PubMed: 38923187
DOI: 10.1111/1756-185X.15218 -
Rheumatology and Therapy Jun 2024A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other...
INTRODUCTION
A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab.
METHODS
Individual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI).
RESULTS
At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure.
CONCLUSIONS
Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered.
PubMed: 38916823
DOI: 10.1007/s40744-024-00684-z