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Quantitative syndesmophyte measurement in ankylosing spondylitis using CT: longitudinal validity and sensitivity to change over 2?years.

ABSTRACT: OBJECTIVES:Accurate measurement of syndesmophyte development and growth in ankylosing spondylitis (AS) is needed for studies of biomarkers and of treatments to slow spinal fusion. We tested the longitudinal validity and sensitivity to change of quantitative measurement of syndesmophytes using CT. METHODS:We performed lumbar spine CT scans on 33 patients with AS at baseline, 1?year and 2?years. Volumes and heights of syndesmophytes were computed in four intervertebral disk spaces. We compared the computed changes to a physician's ratings of change based on CT scan inspection. Sensitivity to change of the computed measures was compared with that of the modified Stoke AS Spinal Score (radiography) and a scoring method based on MRI. RESULTS:At years 1 and 2, respectively 24 (73%) and 26 (79%) patients had syndesmophyte volume increases by CT. At years 1 and 2, the mean (SD) computed volume increases per patient were, respectively 87 (186) and 201 (366) mm(3). Computed volume changes were strongly associated with the physician's visual ratings of change (p<0.0002 and p<0.0001 for changes at years 1 and 2, respectively). The sensitivity to change over 1?year was higher for the CT volume measure (1.84) and the CT height measure (1.22) than either the MRI measure (0.50) or radiography (0.29). CONCLUSIONS:CT-based syndesmophytes measurements had very good longitudinal validity and better sensitivity to change than radiography or MRI. This method shows promise for longitudinal clinical studies of syndesmophyte development and growth.

SUBMITTER: Tan S

PROVIDER: S-EPMC5069457 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Quantitative syndesmophyte measurement in ankylosing spondylitis using CT: longitudinal validity and sensitivity to change over 2 years.

Tan Sovira S Yao Jianhua J Flynn John A JA Yao Lawrence L Ward Michael M MM

Annals of the rheumatic diseases 20131202 2

<h4>Objectives</h4>Accurate measurement of syndesmophyte development and growth in ankylosing spondylitis (AS) is needed for studies of biomarkers and of treatments to slow spinal fusion. We tested the longitudinal validity and sensitivity to change of quantitative measurement of syndesmophytes using CT.<h4>Methods</h4>We performed lumbar spine CT scans on 33 patients with AS at baseline, 1 year and 2 years. Volumes and heights of syndesmophytes were computed in four intervertebral disk spaces. ...[more]

PMID: 24297375

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Project description:ObjectivesAnkylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the sacroiliac joint and spine. However, the real mechanisms of immune cells acting on syndesmophyte formation in AS are not well identified. We aimed to find the key AS-associated cytokine and assess its pathogenic role in AS.MethodsA protein array with 1000 cytokines was performed in five AS patients with the first diagnosis and five age- and gender-matched healthy controls to discover the differentially expressed cytokines. The candidate differentially expressed cytokines were further quantified by multiplex protein quantitation (3 AS-associated cytokines and 3 PDGF-pathway cytokines) and ELISA (PDGFB) in independent samples (a total of 140 AS patients vs 140 healthy controls). The effects of PDGFB, the candidate cytokine, were examined by using adipose-derived stem cells (ADSCs) and human fetal osteoblast cell line (hFOB1.19) as in vitro mesenchymal cell and preosteoblast models, respectively. Furthermore, whole-transcriptome sequencing and enrichment of phosphorylated peptides were performed by using cell models to explore the underlying mechanisms of PDGFB. The xCELLigence system was applied to examine the proliferation, chemotaxis, and migration abilities of PDGFB-stimulated or PDGFB-unstimulated cells.ResultsThe PDGF pathway was observed to have abnormal expression in the protein array, and PDGFB expression was further found to be up-regulated in 140 Chinese AS patients. Importantly, PDGFB expression was significantly correlated with BASFI (Pearson coefficient/p value = 0.62/6.70E - 8) and with the variance of the mSASSS score (mSASSS 2 years - baseline, Pearson coefficient/p value = 0.76/8.75E - 10). In AS patients, preosteoclasts secreted more PDGFB than the healthy controls (p value = 1.16E - 2), which could promote ADSCs osteogenesis and enhance collagen synthesis (COLI and COLIII) of osteoblasts (hFOB 1.19). In addition, PDGFB promoted the proliferation, chemotaxis, and migration of ADSCs. Mechanismly, in ADSCs, PDGFB stimulated ERK phosphorylation by upregulating GRB2 expression and then increased the expression of RUNX2 to promote osteoblastogenesis of ADSCs.ConclusionPDGFB stimulates the GRB2/ERK/RUNX2 pathway in ADSCs, promotes osteoblastogenesis of ADSCs, and enhances the extracellular matrix of osteoblasts, which may contribute to pathological bone formation in AS.

Project description:ObjectiveThe aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS).MethodsBaseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31-743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640-819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs.ResultsA total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p = 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant.ConclusionSecukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.

Project description:IntroductionClinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score < 1.3), ASAS-PR or BASDAI score ≤ 2.MethodsThe analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored.ResultsAt week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI ≤ 2 (22.3 vs. 6.4%) criteria (all P < 0.0001), which were sustained through 156 weeks. Shift analysis showed that the majority of secukinumab-treated patients achieving remission at week 16 maintained their status at week 156 (ASDAS-ID, 57.1%; ASAS-PR, 68.0% and BASDAI ≤ 2, 74.3%). Remission was also associated with improved PROs over 156 weeks.ConclusionsSecukinumab-treated patients maintained ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 from week 16 up to 3 years. Patients who achieved at least one of the three responses/states, reported improvement in PROs, which suggests an association of clinical remission/ID with PROs in patients with active AS.Trial registrationClinicalTrials.gov: NCT01358175, NCT01863732, and NCT01649375.

Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

Dataset Information

Quantitative syndesmophyte measurement in ankylosing spondylitis using CT: longitudinal validity and sensitivity to change over 2?years.

Publications

Quantitative syndesmophyte measurement in ankylosing spondylitis using CT: longitudinal validity and sensitivity to change over 2 years.

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