Stoke Ankylosing Spondylitis Spine Score Research Articles

The burden of spine structural damage on the function in patients with axial spondyloarthritis: adaptation-mediated uncoupling?

To investigate the association between spinal damage and functional capacity in patients with axial spondyloarthritis (axSpA) and to compare the performance of two radiographic scores [modified Stoke AS Spine Score (mSASSS) and Combined AS Spine Score (CASSS)]. Radiographs from 101 axSpA patients were scored according to de Vlam et al. for cervical facet joints (CFJ) and mSASSS for vertebral bodies. CASSS was calculated as the sum of both scores. Physical function was assessed by BASFI; disease activity by BASDAI and AS Disease Activity Score (ASDAS); mobility by BASMI; and quality of life by AS Quality of Life (ASQoL). Univariate and multivariate analyses were performed to investigate the association between possible explanatory variables and outcomes. BASFI correlated strongly with ASQoL (Spearman ρ 0.66) and BASDAI (ρ 0.70), moderately with BASMI (ρ 0.46) and ASDAS (ρ 0.59), and weakly with mSASSS (ρ 0.29) and CASSS (ρ 0.28). A best-fit multivariate model for BASFI, adjusted for symptom duration, age, sex, and smoking status, included BASDAI (B 0.76; P < 0.001), BASMI (B 0.62; P < 0.001) and history of total hip arthroplasty (B 1.22; P = 0.05). Radiographic scores were predictors of BASFI only when BASMI was removed from the model: mSASSS (B 0.03; P = 0.01) and CASSS (B 0.02; P = 0.005). Spinal damage was independently associated with physical function in axSpA but to a lesser extent than disease activity and mobility. Moreover, incorporating CFJ assessment in the mSASSS did not improve the ability to predict function.

Effect of Secukinumab Versus Adalimumab Biosimilar on Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: Results From a Head-to-Head Randomized Phase IIIb Study.

Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was tocompare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor). Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports.

Navigating the Factors Affecting Functional impairment in Spondyloarthritis

Objectives: To assess the predictive factors of functional impairment in SpA patients assessed with BASFI (Bath Ankylosing Spondylitis Functional Index) and LI (Lequesne Index). Methods: We conducted a retrospective study that included SpA patients. Socio-demographics and disease-related data were reported (data collection spread over four months from August 2019 to November 2019). Disease activity was assessed using the Bath Ankylosing Spondylitis-Global score (BASG-s) and the Bath Ankylosing Spondylitis disease activity Index (BASDAI). The spinal mobility was evaluated by The Bath Ankylosing Spondylitis Metrology Index (BASMI). Structural progression was evaluated with The Bath Ankylosing Spondylitis Radiologic Index (BASRI) and modified Stoke ankylosing spondylitis spine score (mSASSS). We conducted a multivariate analysis to search for predictive factors associated with BASFI and LI. Significance was accepted for a p &lt; 0.05 for all statistical tests. Results: Two hundred and sixty-three patients were included. Mean age of the patients was 38.9 ±12.7 years, sex-ratio=2.7. Mean age of onset of SpA was 27.6 ± 10.8. Disease duration was 11.3 ±9.5 years. Occupation was significantly associated with BASFI score and LI. A significant functional impact was significantly correlated with a long duration of the disease. The two scores were correlated with a limitation of spinal mobility (BASMI), a greater disease activity (BASDAI and ESR) and a greater impact of the disease on health status (BASG-s). Significant functional impairment was also correlated with structural impairment: mSASSS, BASRI and sacroiliitis grade. The variables independently related to BASFI were the mSASSS score and the BASDAI. The variables independently related to LI were the profession (unemployed subjects had higher scores), mSASSS score, and the BASMI. Conclusion: Occupation, disease activity, mobility and structural progression predicted functional impairment in Tunisian SpA patients.&#x0D; Keywords: Spondyloarthritis; North Africa; Function; Impairment.

Probability of the 10-year Risk of Hip and Major Osteoporotic Fracture in Non-radiographic Axial Spondyloarthritis.

Fracture risk in non-radiographic spondyloarthritis is underestimated. A reliable tool such as the Fracture Risk Assessment tool (FRAX) may assess this risk probability. This study aimed to assess the fracture risk by the FRAX score in patients with nr-axSpA and to determine factors associated with high fracture risk. We conducted a retrospective study of nr-axSpA patients meeting the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for spondyloarthritis. All patients had Bone Mineral Density (BMD) by dual-energy X-ray absorptiometry (DEXA). The 10- year probability of major osteoporotic fracture (MOF) and hip fracture (HF) was calculated using the Fracture Risk Assessment Tool (FRAX). Among 40 patients with nr-axSpA, 27 were women (67.5%). Their mean age was 43.7 ± 12.1 years. The mean disease duration was 3.15 ± 2.7 years. Eighteen patients (45%) had osteopenia, and 12 patients (30%) had osteoporosis. The median HF FRAX was 0% [0-1.2]. The median MOF FRAX was 0.5% [0.3-1.8]. MOF FRAX was positively correlated with age (p = 0.002), disease onset age (p = 0.006), disease duration (p = 0.024), and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) (p < 0.0001), and negatively correlated with daily calcium intake (p < 0.0001). HF FRAX was positively correlated with mSASSS (p < 0.0001) and negatively correlated with daily calcium intake (p = 0.005). Our study confirmed the frequency of bone loss during nr-axSpA and showed that osteoporotic risk fracture was related not only to traditional risk factors for osteoporosis but also to disease-related factors.

Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial

ObjectivesThe study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on...

Male spondyloarthritis patients and those with longer disease duration have less severe disc degeneration: propensity score-matched comparison.

Using whole spine sagittal T2 MRI, we aimed to compare the severity and prevalence of disc degeneration (DD) in axial SpA patients vs the general population and to determine any association between spinal inflammation, structural changes, mobility and DD among SpA patients. Two prospectively collected cohorts of SpA patients (n = 411) and the general population (n = 2007) were recruited. Eventually, 967 participants from the populational cohort and 304 participants from the SpA cohort were analysed. Two hundred and nineteen matched pairs were generated by propensity score matching. Imaging parameters, including Pfirrmann grading, disc herniation, high-intensity zone, Schmorl's node, Modic change and anterior marrow change were studied and compared from C2/3 to L5/S1. DD was defined as Pfirrmann grade 4 or 5. Demographic factors, including age, sex and BMI, were collected. Multivariable linear regression was used to determine the association between spinal inflammation [Spondyloarthritis Research Consortium of Canada (SPARCC) spine MRI index], structural changes [modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)] and mobility (BASMI) with lumbar Pfirrmann score. SpA patients had lower prevalence of DD (P < 0.001). The disease stage-stratified regression model showed that SPARCC spinal MRI index was associated with higher lumbar Pfirrmann scores in early disease (β = 0.196, P = 0.044), whereas mSASSS was associated with lower lumbar Pfirrmann scores in later disease (β = -0.138, P = 0.038). Males had higher mSASSS (P < 0.001) and lower odds of whole spine DD (odds ratio = 0.622, P = 0.028). SpA patients had lower DD severity than the general population. Males had higher mSASSSs, and increased mSASSS at later disease was associated with less severe DD.

A novel biomarker of MMP-cleaved cartilage intermediate layer protein-1 is elevated in patients with rheumatoid arthritis, ankylosing spondylitis and osteoarthritis

Rheumatic joints have an altered cartilage turnover. Cartilage intermediate layer protein 1 (CILP-1) is secreted from articular chondrocytes and deposited into the cartilage extracellular matrix. We developed an immunoassay targeting a Matrix Metalloproteinase (MMP)-generated neo-epitope of CILP-1, named CILP-M. Human articular cartilage was cleaved with proteolytic enzymes and CILP-M levels were measured. We also quantified CILP-M in two studies from patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteoarthritis (OA) and explored the monitoring and prognostic potential of CILP-M in TNF-α inhibitory treatment and modified Stoke AS Spine Score (mSASSS) progression. CILP-M was generated by MMP-1, -8 and -12. In the discovery study, CILP-M was significantly higher in patients with RA, AS and OA than healthy donors (p < 0.01, p < 0.001, p < 0.05) with an area under the curve (AUC) between the diseased groups and healthy donors > 0.95 (p < 0.001). In the validation study, patients with RA and AS had significantly higher CILP-M levels than healthy controls (p < 0.001) and AUC > 0.90 (p < 0.001). Patients with AS treated with TNF- α inhibitory treatment in the validation study had significantly lower CILP-M levels after treatment (p = 0.004). CILP-M may provide useful insights into cartilage degradation processes in rheumatic diseases.

The Effect of Two Years of Secukinumab Treatment on Bone Metabolism in Patients with Radiographic Axial Spondyloarthritis: Results from Daily Clinical Practice.

Our objective was to explore bone-related outcome and bone turnover markers (BTM) during 2 years of secukinumab treatment in patients with radiographic axial spondyloarthritis (r-axSpA) in daily clinical practice. Included were consecutive r-axSpA outpatients from the Groningen Leeuwarden axSpA (GLAS) cohort treated with secukinumab for 2 years. At baseline and 2 years, spinal radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; 0-72), cervical facet joint involvement according the "de Vlam" scoring method (0-15) and radiographic vertebral fractures (VF) using the "Genant" method (grade 0-3). At all visits, BTM reflecting collagen resorption (serum type I collagen C-telopeptide; sCTX), collagen formation (procollagen type 1 N-terminal peptide; PINP) and bone mineralization (bone-specific alkaline phosphatase; BALP) were measured and expressed in Z-scores to correct for the normal influence of age and gender. 17 r-axSpA patients were included; 53% male, mean age was 47±15 years, mean Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.9±1.2, and 53% was biological naïve. The median 2-year progression rates were 1.1 for mSASSS and 0.5 for facet joints, which was less than the smallest detectable change. One traumatic VF (grade 3) occurred. Serum levels of sCTX and PINP remained stable during secukinumab treatment and BALP decreased significantly after 2 years, with median 0-2 year change in Z-scores of +0.1, -0.4, and -1.2, respectively. This explorative study of r-axSpA patients treated with secukinumab in daily clinical practice showed low radiographic spinal progression during 2 years of follow-up. Collagen resorption and formation markers remained stable, whereas mineralization marker BALP decreased significantly after 2 years. Our results are in line with the results of in vitro studies demonstrating that inhibition of IL17-A resulted in suppression of osteogenic differentiation with significant decrease in mineralization.

Specific descriptions of axial involvement are associated with radiographic damage development after 2 years in psoriatic arthritis patients

ObjectivesInvestigating the association between different definitions of axial involvement and syndesmophytes development over 2 years in patients with psoriatic arthritis (PsA).MethodsPatients from a prospective multicentre cohort (Belgian Epidemiological Psoriatic Arthritis...

Association of radiological severity of hip involvement with clinical characteristics and sagittal spinopelvic balance in patients with ankylosing spondylitis.

This is the first study to analyze the associations between the radiological severity of hip involvement with clinical characteristics and sagittal spinopelvic balance in patients with ankylosing spondylitis (AS). We evaluated 182 patients with AS who were referred to outpatient clinics. Patient demographic data and clinical and radiographic parameters were collected. Patients were divided into three groups based on the Bath Ankylosing Spondylitis Radiology Hip Index. Clinical characteristics and spinopelvic parameters acquired by a low-dose biplanar imaging system were evaluated among these groups. Patients with more severe hip involvement were older and had longer disease duration and diagnostic delay, with lower Harris Hip Score (p < 0.001) and 12-item Short Form Health Survey Physical Component Score (p < 0.001) and higher Bath Ankylosing Spondylitis Disease Activity Index (p = 0.030) and Functional Index (p < 0.001). Patients with more severe hip involvement had significantly higher sacroiliac grade (p < 0.001) and higher modified Stoke Ankylosing Spondylitis Spinal Score (p < 0.001). Patients with moderate and severe hip involvement had similar lumbar lordosis and spino-sacral angle, whereas patients with severe hip involvement had lower pelvic tilt, pelvic femoral angle, higher sacral slope, and sagittal vertical axis. The severity of hip involvement is associated with physical function and is not consistent with the severity of spinal involvement. Severe hip involvement impairs the ability to retrovert the pelvis to accommodate the sagittal deformity, and spinopelvic parameters should be concretely evaluated in preoperative counseling of patients with AS waiting for total hip arthroplasty. Key Points • The severity of hip involvement in patients with AS is associated with physical function. • Severe hip involvement impairs the ability to retrovert the pelvis to accommodate the sagittal deformity.

Physical function and sex differences in radiographic axial spondyloarthritis: a cross-sectional analysis on Bath Ankylosing Spondylitis Functional Index

BackgroundPhysical function is an important determinant of health-related quality of life in radiographic axial spondyloarthritis patients (r-axSpA). To improve the basis of effective healthcare efforts, we aimed to investigate which demographic and disease-related factors that influence Bath Ankylosing Spondylitis Functional Index (BASFI) in r-axSpA patients overall and stratified by sex. Furthermore, we sought to explore differences between sexes regarding separate BASFI questions and also to explore which factors that may contribute to these differences.MethodsThis observational cross-sectional study included patients fulfilling the modified New York criteria for Ankylosing Spondylitis. Patients were assessed with 66/68 joint count and Bath Ankylosing Spondylitis Metrology Index (BASMI) measurements. Lateral X-rays were performed for Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP), and BASFI were registered. Multivariable linear regression analyses were used to investigate which factors that associate with BASFI.ResultsA total of 353 r-axSpA patients were included, mean age 52.2 ± 12.7 years, 62.3% males. No significant sex difference was seen in BASFI scores (2.7 ± 2.0 in males vs 2.9 ± 2.1 in females). Age, body mass index, ASDAS-CRP, BASMI or mSASSS, fatigue, and tenderness were found to associate independently with BASFI in different models (R2 0.53–0.63). Investigation of separate BASFI questions revealed that the ability to look over shoulder was worse in males than females (mean 4.43 ± 3.37 vs 3.74 ± 3.06, p = 0.05) and most strongly correlated with mSASSS and BASMI among separate BASFI questions (r = 0.53, p < 0.001; r = 0.62, p < 0.001). The ability to climb stairs was worse in females than males (mean 2.49 ± 2.77 vs 1.54 ± 2.32, p < 0.001).ConclusionsNo difference between male and female r-axSpA patients was seen in BASFI despite significant sex differences in BASMI, mSASSS, and CRP levels. Our results underline the impact of fatigue and tenderness on BASFI. The ability to climb stairs without a handrail was scored worse among females compared to males. Furthermore, the ability to look over the shoulder was worse in males than females and closely related to spinal mobility and structural spinal changes.

Costovertebral and costotransverse joint involvement in spondyloarthritis.

Costovertebral (CV), costotransverse (CTr), sternoclavicular (SC), and manubriosternal (MS) joints are impacted in spondyloarthritis (SpA) patients; however, clinical aspects of these involvements require additional evaluation. A total of 281 SpA patients who had undergone chest computed tomography (CT) for any reason between 2010 and 2020 were included in the study. SpA patients were divided into three groups, ankylosing spondylitis (AS), non-radiographic axial SpA, and psoriatic arthritis. Thirty age- and sex-matched rheumatoid arthritis (RA) patients and 30 non-rheumatic disease individuals were selected for comparison. An experienced radiologist reviewed 24 CV, 20 CTr, 2 SC, and 1 MS joints from a thorax CT for each patient. All joints were classified as: normal (0); suspicious (1), mild (2), moderate (3), or severe (4). Total CV and CTr joint scores differed between diseases (p < .001). Male AS patients had higher CV and CTr scores than female AS patients (male CV score: 52 [range 0-96] and CTr score: 22 [range 0-80]; female CV score: 20 [range 0-96] and CTr score: 12 [range 0-79]). Strong negative correlations were detected in AS patients between chest expansion and CV (r = -0.703 p = .007) and CTr (r = -0.763 p = .002) joint involvement; positive correlations between CV and CTr joints, and modified Stoke Ankylosing Spondylitis Spinal Score (p < .05); and no significant association for MS and SC joints. CV and CTr joint involvement on thorax CT was more severe in AS and negatively affected chest expansion. The use of thorax CT scans performed for other indications in the examination of these joints may be advantageous for the early beginning of rehabilitation programs targeted at maintaining chest mobility.

DNA methylation of DKK-1 may correlate with pathological bone formation in ankylosing spondylitis.

To investigate DNA methylation (DNAm) status of dickkopf-associated protein 1 (DKK-1) in ossified hip capsule synovium and serum among patients with ankylosing spondylitis (AS). Western blot was applied to detect the level of DKK-1 protein expression in hip joint capsule tissues from four patients with AS as well as four patients with femoral neck fracture (FNF) caused by trauma as control. DKK-1 gene promoter methylation (GPM) was examined by methylation-specific polymerase chain reaction. Reverse transcription-polymerase chain reaction was performed to examine the messenger RNA (mRNA) levels of DKK-1, β-catenin, and Wnt3a in both tissue and serum. The DNAm status of serum DKK-1 was measured among 36 patients with AS and syndesmophytes (AS + syndesmophytes group), 40 patients with AS but no syndesmophyte (AS group), and 42 healthy individuals (control group). Also, the serum levels of DKK-1 were measured by enzyme-linked immunosorbent assay. The modified New York criteria (mNYC) together with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were adopted to examine the radiographic progression of AS. The receiver operating characteristic (ROC) curve was applied to investigate the diagnostic value of the methylation rate of DKK-1 with regard to radiographic progression. The expressions of DKK-1 protein and mRNA in hip joint capsule tissues of AS patients were significantly lower, while DKK-1 GPM rate, β-catenin mRNA, and Wnt3a mRNA were markedly higher when compared with FNF group. For serum samples, the DKK-1 methylation rate was significantly higher in AS+ syndesmophytes group in contrast to AS group and healthy controls. Serum levels of DKK-1 protein and mRNA in AS with syndesmophytes group were markedly decreased, while β-catenin mRNA and Wnt3a mRNA expressions were significantly increased than AS with no syndesmophyte group and the healthy control group. AS patients in Grade 4 showed a significantly higher serum DKK-1 GPM rate than those in Grade 3 based on mNYC. Serum DKK-1 GPM level was markedly and positively correlated with mSASSS. Serum levels of DKK-1 in AS+ syndesmophytes group were markedly lower compared with AS but no syndesmophyte group and healthy controls. ROC curve analysis indicated that serum DKK-1 methylation rate serves as a decent indicator for AS radiographic progression. DNAm of DKK-1 may correlate with pathological bone formation in AS, which may provide new strategies for the treatment of AS abnormal bone formation.

Impact of sex on spinal radiographic progression in axial spondyloarthritis: a longitudinal Swiss cohort analysis over a period of 10 years

ObjectiveTo investigate sex differences in spinal radiographic progression in axial spondyloarthritis (axSpA).MethodsAxSpA patients in the Swiss Clinical Quality Management cohort with available spinal radiographs every 2 years were included. Paired...

Anaemia is associated with higher disease activity in axial spondyloarthritis but is not an independent predictor of spinal radiographic progression: data from the Swiss Clinical Quality Management Registry

ObjectiveAs anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA).MethodsAxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values.ResultsA total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years.ConclusionAlthough anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression.Key Points• Anaemia is associated with higher disease activity and more severely impaired physical function, mobility and quality of life in axSpA.• Anaemia does not provide an additional value to ASDAS for prediction of spinal radiographic progression.

Radiographic involvement of cervical facet joints in ankylosing spondylitis: a longitudinal analysis in correlation with vertebral body lesions

BackgroundThe inability to assess structural changes in facet joints is a limitation of established radiographic scoring systems for ankylosing spondylitis (AS). We compared radiographic evidence of ankylosis in cervical facet joints and cervical vertebral bodies in patients with AS.MethodsWe analysed longitudinal data collected from 1106 AS patients and assessed 4984 spinal radiographs obtained up to 16 years of follow-up. Comparisons between cervical facet joints and cervical vertebral bodies focused on the presence of ankylosis, which was defined by at least one facet joint exhibiting complete ankylosis (according to the method of de Vlam) or at least one vertebral body with a bridging syndesmophyte (according to the modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). Ankylosis was assessed over time using spinal radiographs collected during follow-up periods stratified in 4-year increments.ResultsPatients with cervical facet joint ankylosis had higher cervical mSASSS, sacroiliitis grades, and inflammatory markers, with more prevalent hip involvement and uveitis. Overall, the numbers of spinal radiographs indicating ankylosis were comparable between cervical facet joints (17.8%) and cervical vertebral bodies (16.8%), and they usually presented together (13.5%). We observed similar proportions of radiographs with ankylosis only in cervical facet joints (4.3%) and cervical vertebral bodies (3.3%). As damage progressed, configurations with both cervical facet joint ankylosis and bridging syndesmophytes became more predominant with longer follow-up times, while configurations with cervical facet joint ankylosis only or bridging syndesmophytes only were less frequently observed.ConclusionsEvidence of cervical facet joint ankylosis appears as often as bridging syndesmophytes on routine AS spinal radiographs. Presence of cervical facet joint ankylosis should be considered because it may have a higher disease burden.

Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis

This retrospective study evaluated the electronic medical records of patients with ankylosing spondylitis (AS) (January 2001–December 2018) to determine the relationship between serum alkaline phosphatase (ALP) levels and radiographic changes over time. Longitudinal data, including serum ALP levels, were imputed by linear interpolation at 3-month intervals. Among the serum ALP levels calculated for 8 years prior to modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) measurement, those having the highest beta coefficient with the mSASSS were selected in the correlation between ALP and longitudinal mSASSS. Linear mixed models with the selected serum ALP levels, mSASSS, and clinical variables were investigated. We included 1122 patients (mean follow-up, 8.20 [standard deviation: 2.85] years). The serum ALP level from 5 years and 3 months prior showed the highest beta coefficient with the mSASSS. In the linear mixed model, the serum ALP level at 5 years and 3 months before radiographic changes was significantly associated with the mSASSS (β = 0.021, 95% confidence interval: 0.017–0.025, p < 0.001). Serum ALP levels measured approximately 5 years before may be a surrogate marker for predicting spinal radiographic changes. Long-term prospective clinical and experimental studies of > 5 years are required for biomarker discovery or therapeutic research on AS radiographic progression.

Comparison of radiological changes in symphysis pubis and disease activity parameters in male patients with ankylosing spondylitis

Introduction: To determine the prevalence of involvement of symphysis pubis among male patients with ankylosing spondylitis (AS) and to analyze the relationship among this involvement, demographic data, clinical activity of the disease and radiological findings. Methods: Overall, 73 male patients diagnosed with AS who visited our clinic for follow-up were included in the study. In this retrospective study, clinical and radiological parameters were collected. In clinical evaluation, vertebral Visual Analog Scale (VAS) score, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were used. In AP pelvis radiography, symphysis pubis changes were rated as 0–4. Modified Stoke Ankylosing Spondylitis Spinal Score (M-SASSS) was calculated from the cervical and lumbar lateral radiography images. Results: Symphysis pubis involvement was radiologically observed in 45 patients (61.7%). The mean age (43.9 ± 12.6) of patients with symphysis pubis involvement was higher than the average (36.9 ± 9.0) of patients without involvement (p = 0.026). Average M-SASSS of patients with symphysis pubis involvement (15.9 ± 11.9) was higher than the average of patients without involvement (8.4 ± 7.4), and there was a significant positive correlation between symphysis pubis involvement and M-SASSS (p=0.002). BASDAI and BASMI averages of patients were not significant (p = 0.973 and p = 0.105, respectively). Conclusion: Symphysis pubis involvement is a common manifestation of AS and can be used to predict vertebral radiological involvement. Keywords: Ankylosing Spondylitis, Symphysis Pubis, Modified Stoke Ankylosing Spondylitis Spinal Score

Two-year imaging outcomes from a phase 3 randomized trial of secukinumab in patients with non-radiographic axial spondyloarthritis

BackgroundRadiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here.MethodsIn the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or placebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0–8) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; range, 0–72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0–24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0–69).ResultsOverall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, − 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase ≤ smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n = 7) and 2.9% (n = 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNY-negative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syndesmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed ≥ 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], − 1.23 [2.81] vs − 0.37 [1.90] with placebo) was sustained through week 104 (− 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104).ConclusionStructural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years.Trial registrationClinicalTrials.gov, NCT02696031.

Abnormal kynurenine level contributes to the pathological bone features of ankylosing spondylitis.

Ankylosing spondylitis (AS) exhibits paradoxical bone features typically characterized by new bone formation and systemic bone loss. Although abnormal kynurenine (Kyn), a tryptophan metabolite, has been closely linked to the disease activity of AS, the distinct role of its pathological bone features remains unknown. Kynurenine sera level was collected from healthy control (HC; n=22) and AS (n=87) patients and measured by ELISA. In the AS group, we analyzed and compared the Kyn level based on the modified stoke ankylosing spondylitis spinal score (mSASSS), MMP13, and OCN. Under osteoblast differentiation, the treatment with Kyn in AS-osteoprogenitors conducted cell proliferation, alkaline phosphatase activity, bone mineralization-related alizarin red s (ARS), von kossa (VON), hydroxyapatite (HA) staining, and mRNA expression markers (ALP, RUNX2, OCN, and OPG) for bone formation. TRAP and F-actin staining was used for osteoclast formation of mouse osteoclast precursors. Kyn sera level was significantly elevated in the AS group compared to the HC. In addition, Kyn sera level was correlated with mSASSS (r=0.03888, p=0.067), MMP13 (r=0.0327, p=0.093), and OCN (r=0.0436, p=0.052). During osteoblast differentiation, treatment with Kyn exhibited no difference in cell proliferation and alkaline phosphate (ALP) activity for bone matrix maturation but promoted ARS, VON, and HA staining for bone mineralization. Interestingly, osteoprotegerin (OPG) and OCN expressions of AS-osteoprogenitors were augmented in the Kyn treatment during differentiation. In growth medium, Kyn treatment of AS-osteoprogenitors resulted in induction of OPG mRNA, protein expression, and Kyn-response genes (AhRR, CYP1b1, and TIPARP). Secreted OPG proteins were observed in the supernatant of AS-osteoprogenitors treated with Kyn. Notably, the supernatant of Kyn-treated AS-osteoprogenitors interrupted the RANKL-mediated osteoclastogenesis of mouse osteoclast precursor such as TRAP-positive osteoclast formation, NFATc1 expression, and osteoclast differentiation markers. Our results revealed that elevated Kyn level increased the bone mineralization of osteoblast differentiation in AS and decreased RANKL-mediated osteoclast differentiation by inducing OPG expression. Out study have implication for potential coupling factors linking osteoclast and osteoblast where abnormal Kyn level could be involved in pathological bone features of AS.