mSASSS Units Research Articles

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.

Site-specific assessment of spinal radiographic progression improves detection of TNF blocker-associated disease modification in axial spondyloarthritis: longitudinal observational data from the Swiss Clinical Quality Management Registry

ObjectivesTo analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine).MethodsPatients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years.ResultsMean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p = 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14–0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52–1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24–0.77 and 0.85, 95% CI 0.51–1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12–0.80 versus OR 0.56, 95% CI 0.26–1.24 for the cervical and lumbar spine, respectively).ConclusionDisease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA.

Current differentiation between radiographic and non-radiographic axial spondyloarthritis is of limited benefit for prediction of important clinical outcomes: data from a large, prospective, observational cohort

ObjectiveTo compare disease characteristics and outcomes between patients with axial spondyloarthritis with non-radiographic disease (nr-axSpA), bilateral grade 2 sacroiliitis (r22axSpA) and unilateral/bilateral grade 3–4 sacroiliitis (r3+axSpA) according to the modified...

Sustained low disease activity measured by ASDAS slow radiographic spinal progression in axial spondyloarthritis patients treated with TNF-inhibitors: data from REGISPONSERBIO

BackgroundTo evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi).MethodsThe study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: (i) long-term treatment (≥4 years) and (ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients’ groups at each time point were assessed using a linear mixed-effect model.ResultsRadiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP).ConclusionsPatients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

Factors Predictive of Radiographic Progression in Ankylosing Spondylitis.

Using a longitudinal observational cohort of ankylosing spondylitis (AS) patients, we sought to identify progression rates and factors predictive of spinal progression. As a secondary aim, we analyzed the effect of tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression. AS patients who had baseline and follow-up cervical and lumbar radiographs were included in the study. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A change of 2 mSASSS units in 2 years was defined as progression. The characteristics of the study group such as demographic, clinical, laboratory, and treatment history were collected. There were 350 patients in the study. The mean ± SD mSASSS increased from 9.3 ± 15.8 units at baseline to 17.7 ± 21.7 units by the sixth year. Mean ± SD changes in mSASSS between the years 0 to 2, 2 to 4, and 4 to 6 were 1.23 ± 2.68, 1.47 ± 2.86, and 1.52 ± 3.7 units, respectively. Overall, 24.3% of the group progressed over 2 years. Male sex (hazard ratio [HR] 2.46 [95% confidence interval (95% CI) 1.05, 5.76]), the presence of baseline damage (HR 7.98 [95% CI 3.98, 16]), increased inflammatory markers (log C-reactive protein level HR 1.35 [95% CI 1.07, 1.70]), and TNFi use (HR 0.82 [95% CI 0.70, 0.96]) were predictive of radiographic progression. There was a 20% reduction in the rate of progression with TNFi. Male sex, the presence of baseline damage, active disease state, and higher inflammatory markers confer a high risk for disease progression. Treatment with TNFi showed a disease-modifying effect by slowing the rate of radiographic progression.

Effect of TNF-inhibitor therapy on spinal structural progression in ankylosing spondylitis patients: A systematic review and meta-analysis.

To review the effect of tumor necrosis factor-alpha inhibitor (TNFi) therapies on radiographic progression in ankylosing spondylitis (AS) patients as evaluated by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Pubmed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from inception to August 2019. All comparative and non-comparative studies that evaluated the clinical effectiveness of TNFi on radiographic progression as assessed by mSASSS change at a minimum follow-up of 1year were included. The Newcastle-Ottawa Scale and Cochrane Collaboration Risk of Bias Tool were utilized to assess the methodological quality. Pooled analysis was performed for continuous and binomial variables where appropriate. Inter-rater reliability of mSASSS status and change scores were assessed with intra-class coefficients (ICC). Twenty-one studies were identified with a total of 4460 patients (mean age: 40.4years [range 25.3-50years]; 76% male; mean baseline mSASSS: 12.7 units [range 5.5-19.8 units]). All studies (3 randomized and 18 observational studies) were considered to have moderate-to-high methodological quality. The inter-rater reliability of mSASSS status and change scores from 14 of the 21 studies were excellent (ICC ranges, 0.91-0.99) and moderate-to-excellent (ICC ranges, 0.58-0.90), respectively. From the 21 studies, 11/21 (50%) demonstrated a delayed effect in mSASSS in AS patient administered TNFi. When stratifying these studies into those with ≤4years of follow-up and >4years follow-up, 3/11 (27%) and 8/10 (80%) studies respectively indicated a delayed effect of mSASSS with TNFi in AS patients. Pooling for meta-analysis from 3 studies (1159 patients) with study durations ranging 4-8years, indicated that TNFi-treated patients had reduced odds of structural progression (odds ratio 0.81; 95% CI 0.68-0.96; P=.01; I2 =0%). Mean rate of mSASSS change from 16 studies ranged from -0.15 to 7.3 mSASSS units for all AS patients. Meta-analysis indicated a numerical, but statistically non-significant, reduction in the rate of mSASSS change with TNFi treatment (7 studies [1438 patients]; mean difference, -0.24; 95% CI, -0.49-0.01; P=.06; I2 =0%). This systematic review and meta-analysis indicated that >4years of TNFi usage was associated with delayed structural progression by mSASSS. The narrative analysis of the data from 21 studies further confirmed that studies with >4years of follow-up had delayed structural progression with TNFi use in AS patients. The systematic review also confirmed that mSASSS has good-to-excellent inter-rater reliability in AS.

Spinal radiographic progression in axial spondyloarthritis and the impact of classification as nonradiographic versus radiographic disease: Data from the Swiss Clinical Quality Management cohort.

ObjectiveTo investigate whether spinal radiographic progression relates to structural damage at the sacroiliac level in axial spondyloarthritis (axSpA).MethodsPatients classified as nonradiographic (nr-) and radiographic (r-) axSpA in the Swiss Clinical Quality Management cohort with radiographs performed every 2 years, scored according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), were included. The relationship between classification status and spinal progression during 2 years was investigated using binomial generalized estimating equations models with adjustment for sex, ankylosing spondylitis disease activity score (ASDAS) and tumour necrosis factor inhibitor treatment. Baseline spinal damage was considered an intermediate variable and included in sensitivity analyses.ResultsIn total, 88 nr-axSpA and 418 r-axSpA patients contributed to data for 725 radiographic intervals. R-axSpA patients were more frequently male, had a longer disease duration and higher structural damage at baseline. Mean (SD) mSASSS change over 2 years was 0.16 (0.62) units in nr-axSpA and 0.92 (2.78) units in r-axSpA, p = 0.01. Nr-axSpA was associated with a significantly lower progression in 2 years (defined as an increase in ≥2 mSASSS units) in adjusted analyses (OR 0.33, 95%CI 0.13; 0.83), confirmed with progression defined as the formation of ≥1 syndesmophyte. Mediation analyses revealed that sacroiliitis exerted its effect on spinal progression indirectly by being associated with the appearance of a first syndesmophyte (OR 0.09, 95%CI 0.02; 0.36 for nr-axSpA vs r-axSpA). Baseline syndesmophytes were predictors of further progression.ConclusionSpinal structural damage is mainly restricted to patients with r-axSpA, leading to relevant prognostic and therapeutic implications.

A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis

BackgroundKnowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex.MethodsSwedish patients with AS, age (mean ± SD) 50 ± 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples.ResultsOf 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 ± 2.8 vs. 1.2 ± 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression ≥ 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women.ConclusionThis first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men.Trial registrationClinicalTrials.gov, NCT00858819. Registered on 9 March 2009. Last updated 28 May 2015.

TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort

ObjectivesTo analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS).MethodsPatients with AS in the Swiss Clinical Quality Management cohort with up to...

Spinal radiographic progression in patients with ankylosing spondylitis treated with TNF-α blocking therapy: a prospective longitudinal observational cohort study.

ObjectivesTo evaluate spinal radiographic damage over time and to explore the associations of radiographic progression with patient characteristics and clinical assessments including disease activity in ankylosing spondylitis (AS) patients treated with tumor necrosis factor-alpha (TNF-α) blocking therapy in daily clinical practice.MethodsConsecutive outpatients from the Groningen Leeuwarden AS (GLAS) cohort were included based on the availability of cervical and lumbar radiographs before start of TNF-α blocking therapy and after 2, 4, and/or 6 years of follow-up. Clinical data were assessed at the same time points. Radiographs were scored by two independent readers using the modified Stoke AS Spine Score (mSASSS). Spinal radiographic progression in relation to clinical assessments was analyzed using generalized estimating equations.Results176 AS patients were included, 58% had syndesmophytes at baseline. Median mSASSS increased significantly from 10.7 (IQR: 4.6–24.0) at baseline to 14.8 (IQR: 7.9–32.8) at 6 years. At the group level, spinal radiographic progression was linear with a mean progression rate of 1.3 mSASSS units per 2 years. Both spinal radiographic damage at baseline and radiographic progression were highly variable between AS patients. Male gender, older age, longer disease duration, higher BMI, longer smoking duration, high CRP, and high ASDAS were significantly associated with syndesmophytes at baseline. Significantly more radiographic progression was seen in patients with versus without syndesmophytes (2.0 vs. 0.5 mSASSS units per 2 years) and in patients >40 versus ≤40 years of age (1.8 vs. 0.7 mSASSS units per 2 years). No longitudinal associations between radiographic progression and clinical assessments were found.ConclusionsThis prospective longitudinal observational cohort study in daily clinical practice shows overall slow and linear spinal radiographic progression in AS patients treated with TNF-α blocking therapy. At the individual level, progression was highly variable. Patients with syndesmophytes at baseline showed a 4-fold higher radiographic progression rate than patients without syndesmophytes.

SAT0368 Tumor Necrosis Factor Inhibitor Has NO Influence on Radiographic Damage in Ankylosing Spondylitis: Observation Study of Korean Spondyloarthropathy Registry (OSKAR) Data

ObjectivesTo evaluate the influence of tumor necrosis factor (TNF) blocker on the radiographic damage in ankylosing spondylitis (AS)MethodsA total of 598 TNF blocker naïve AS patients from the Observation Study...

Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12-year longitudinal data from the OASIS cohort

ObjectivesTo analyse the long-term relationship between disease activity and radiographic damage in the spine in patients with ankylosing spondylitis (AS).MethodsPatients from the Outcome in AS International Study (OASIS) were followed...

Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study

ObjectivesTo describe the evolution of radiographic abnormalities of the spine in patients with ankylosing spondylitis (AS).MethodsPatients with AS were followed prospectively with 2 yearly radiographs for 12 years. The modified...

OP0247 Reduction of radiographic spinal progression in patients with ankylosing spondylitis treated with non-steroidal anti-inflammatory drugs is most evident in the presence of syndesmophytes and active systemic inflammation

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are clinically effective and considered as a first line therapy in patients with ankylosing spondylitis (AS). NSAIDs might also have disease-modifying activities retarding radiographic spinal progression...

FRI0468 Socioeconomic status predicts radiographic progression in ankylosing spondylitis

BackgroundLower socioeconomic status (SES) is associated with worse outcomes in several rheumatic diseases. In Ankylosing Spondylitis (AS), SES has been associated with poorer functional outcomes and certain physical activities with...

SAT0252 HLA-B27 Homozygosity has No Influence on Radiographic Damage in Ankylosing Spondylitis: Observation Study of Korean Spondyloarthropathy Registry (OSKAR) Data

BackgroundThere is no consensus as to whether HLA-B27 homozygosity influences the clinical features of ankylosing spondylitis (AS). We already reported that HLA-B27 homozygosity has no influence on clinical and functional...

SAT0248 Evolution of Radiographic Damage in Ankylosing Spondylitis Over 12 Years of Follow-Up

BackgroundRadiographic damage is one of the core outcomes recommended by the ASAS for follow-up of patients with AS. So far, the evolution of radiographic damage over a long period has...

HLA-B27 homozygosity has no influence on radiographic damage in ankylosing spondylitis: Observation Study of Korean spondyloArthropathy Registry (OSKAR) data

ObjectivesTo evaluate the influence of homozygosity for HLA-B27 on the radiographic damage in ankylosing spondylitis (AS). MethodsA total of 368 AS patients with positive HLA-B27 status from the Observation Study of Korean spondyloArthropathy Registry (OSKAR) cohort were recruited for this study. HLA-B27 positive patients out of all AS patients were assessed for whether they had homozygosity or heterozygosity for HLA-B27. First, all data were stratified in relation to the carrier state of positive HLA-B27 for cross-sectional survey. Then we compared the radiographic damage score between groups. Second, we evaluated collected clinical and radiographic parameters at two different time points. Then we compared radiographic progression between groups. To use the mSASSS, cervical and lumbar spinal radiographs were examined by two experienced bone and joint radiologists (S. Lee, K.B. Joo). ResultsThe agreement between the two readers regarding mSASSS was very good: ICC coefficient 0.70 (95% CI 0.60–0.81). The mean age (SD) of the AS patients was 37.0 (9.2) years, and the mean disease duration (SD) was 15.6 (9.1) years. Of these patients, 34.5% (127 patients) had HLA-B27 homozygosity. The mean mSASSS unit (SEM) was not significantly different between groups (homozygosity 28.57±4.12 vs heterozygosity 23.34±3.44, P=0.344) on cross-sectional survey. When it comes to radiographic progression between groups over 5years, there was no significant difference in spite of adjusting for confounding variable (homozygosity 4.98±0.98 vs heterozygosity 4.21±0.82, P=0.562). ConclusionThe carrier state of positive HLA-B27 plays no role in determining the radiographic progression in AS.

Radiographic severity of ankylosing spondylitis is associated with polymorphism of the large multifunctional peptidase 2 gene in the Spondyloarthritis Research Consortium of Canada cohort

There are limited data on genetic predictors of radiographic progression. The aim of this study was to examine polymorphisms in genes involved in antigen presentation and their effect on radiographic severity and progression. Caucasian patients with ankylosing spondylitis (AS) (diagnosed according to the modified New York criteria) from 2 Canadian centers were enrolled. Patients in the progression part of the study had at least 2 sets of radiographs obtained at a minimum gap of 1.5 years, with a modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Peripheral blood DNA was used for genotyping a panel of 13 coding-region single-nucleotide polymorphisms (SNPs) in ERAP1, LMP2, LMP7, TAP1, and TAP2. Linear regression analysis was performed to identify the predictors of the baseline mSASSS and logistic regression for predictors of progression. Progression was defined as an increase of 1 mSASSS unit per year. A total of 241 AS patients (81% males; 82% HLA-B27-positive) were enrolled from the 2 centers for analysis of the predictors of baseline radiographic severity. In univariate analyses, the baseline mSASSS was associated with sex, disease duration, and SNPs rs30187 (ERAP1) and rs17587 (LMP2). In multivariate analyses, duration of disease (B = 0.74; P = 1 × 10(-11) ), sex (B = 12.1; P = 5 × 10(-5) ), and the LMP2 SNP rs17587 (B = 6.2; P = 0.01) were significantly associated with the baseline mSASSS. In multivariate analyses of progression, only the baseline mSASSS was a significant predictor (B = 0.03; P = 0.003). This is the first study to demonstrate that LMP2 variants can affect radiographic severity in AS. The baseline mSASSS remains the strongest predictor of radiographic progression but explains only a fraction of the variability seen.