Stoke Ankylosing Spondylitis Spine Score Research Articles

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.

E089 Effect of secukinumab on radiographic progression and inflammation in sacroiliac joints and spine in patients with non-radiographic axial spondyloarthritis: 2-year imaging outcomes from a Phase III randomised trial

E089 Effect of secukinumab on radiographic progression and inflammation in sacroiliac joints and spine in patients with non-radiographic axial spondyloarthritis: 2-year imaging outcomes from a Phase III randomised trial

Quantitative prediction of radiographic progression in patients with axial spondyloarthritis using neural network model in a real-world setting

BackgroundPredicting radiographic progression in axial spondyloarthritis (axSpA) remains limited because of the complex interaction between multiple associated factors and individual variability in real-world settings. Hence, we tested the feasibility of artificial neural network (ANN) models to predict radiographic progression in axSpA.MethodsIn total, 555 patients with axSpA were split into training and testing datasets at a 3:1 ratio. A generalized linear model (GLM) and ANN models were fitted based on the baseline clinical characteristics and treatment-dependent variables for the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) of the radiographs at follow-up time points. The mSASSS prediction was evaluated, and explainable machine learning methods were used to provide insights into the model outcome or prediction.ResultsThe R2 values of the fitted models were in the range of 0.90–0.95 and ANN with an input of mSASSS as the number of each score performed better (root mean squared error (RMSE) = 2.83) than GLM or input of mSASSS as a total score (RMSE = 2.99–3.57). The ANN also effectively captured complex interactions among variables and their contributions to the transition of mSASSS over time in the fitted models. Structural changes constituting the mSASSS scoring systems were the most important contributing factors, and no detectable structural abnormalities at baseline were the most significant factors suppressing mSASSS change.ConclusionsClinical and radiographic data-driven ANN allows precise mSASSS prediction in real-world settings. Correct evaluation and prediction of spinal structural changes could be beneficial for monitoring patients with axSpA and developing a treatment plan.

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.

Good construct validity of the CT Syndesmophyte Score (CTSS) in patients with radiographic axial spondyloarthritis

ObjectivesTo assess construct validity of the CT Syndesmophyte Score (CTSS) for the measurement of structural spinal damage in patients with radiographic axial spondyloarthritis.MethodsLow-dose CT and conventional radiography (CR) were performed...

Relationship between sex and clinical and imaging features of early axial spondyloarthritis: results from a 48 month follow-up (Italian arm of the SPondyloArthritis Caught Early (SPACE) study)

Objectives To assess the association between sex and clinical and disease activity indices, and X-rays and magnetic resonance imaging (MRI) features, in early-stage axial spondyloarthritis (axSpA). Method Baseline data analysis was conducted on the Italian SPACE cohort, including patients with chronic back pain (duration ≥ 3 months and ≤ 2 years; onset < 45 years). Patients underwent MRI and X-rays of the sacroiliac joints (SIJs) to establish the diagnosis of axSpA, according to Assessment of SpondyloArthritis international Society criteria and physician’s judgement. Clinical features, disease activity and functional indices, and images were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRI images were scored by two readers following Spondyloarthritis Research Consortium of Canada (SPARCC), modified Stoke Ankylosing Spondylitis Spinal Score, and modified New York criteria. Characteristics of axSpA patients according to sex (male/female) were compared over time using descriptive statistics. Results Ninety-one patients had axSpA (83.5% non-radiographic; 16.5% radiographic); 47.3% were male. Males were younger, with shorter duration of axial symptoms, and more frequently had HLA-B27 positivity, radiographic sacroiliitis with a bilateral/symmetric pattern, and more signs of spondylitis. Females more frequently showed peripheral/entheseal involvement and the non-radiographic phenotype. Males showed increased pelvic/spinal radiographic progression and more often had active sacroiliitis on MRI. Although the frequency of inflammatory corner lesions did not differ between males and females, localization varied, with more cervical/thoracic MRI-spine lesions in females and more lumbar lesions in males. We observed a significant downward trend of SPARCC SIJ/spine scores in all patients, irrespective of sex. More fat lesions were observed on MRI-spine in females and on MRI-SIJ in males. Conclusion Sex was associated with distinct axSpA features: females showed low-grade radiographic sacroiliitis and spinal progression, and a higher prevalence of cervical and thoracic spine MRI signs.

Clinical and genetic factors associated with radiographic damage in patients with ankylosing spondylitis

ObjectivesTo identify clinical and genetic factors associated with severe radiographic damage in patients with ankylosing spondylitis (AS).MethodsWe newly generated genome-wide single nucleotide polymorphism data (833K) for 444 patients with AS....

Prevalence and Radiographic Progression of Hip Involvement in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors.

To examine the prevalence of hip involvement between sexes in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor inhibitors (TNFi) and to estimate the effect of TNFi on radiographic progression of hip involvement compared to the spine. Two hundred ninety-nine patients with AS treated with TNFi (215 men; median age: 43 yrs [IQR 36-52], median disease duration: 7.6 yrs [IQR 2-15]) were evaluated for hip involvement, defined radiographically as Bath AS Radiological Hip Index (BASRI-hip) score ≥ 2. Those who received TNFi for ≥ 2 years (263/299) were assessed for radiographic progression. Radiographs of the pelvis and spine, obtained at baseline (ie, before TNFi initiation), were compared retrospectively to those obtained after 2.5 (SD 0.7) years and 7.0 (SD 2.3) years of TNFi treatment. Both hips were scored by BASRI-hip score and mean joint space width (MJSW). Spinal radiographs were scored by modified Stoke AS Spinal Score (mSASSS). The prevalence of hip involvement at baseline was 113/299 (38%) patients, of whom 87/215 (41%) were male and 26/84 (31%) were female (P = 0.10). In both sexes with hip involvement at baseline, BASRI-hip score and MJSW did not change significantly during follow-up. In males and females without baseline hip involvement, the BASRI-hip score remained unchanged after 2.5 (SD 0.7) years but increased significantly after 7.0 (SD 2.3) years, without reaching the cut-off of 2. In contrast, the MJSW slightly decreased at the 2 follow-up timepoints (ie, after 2.5 and 7.0 yrs). The mSASSS increased significantly during the follow-up in both sexes, regardless of hip involvement. In our study, approximately one-third of patients with AS had hip involvement, which seemed to stabilize with TNFi treatment. No sex differences in the prevalence or progression of this manifestation were found.

The impact of smoking status on radiographic progression in patients with ankylosing spondylitis on anti-tumor necrosis factor treatment.

Ankylosing spondylitis (AS) is characterized by back pain which can lead to spinal ankylosis. Anti-tumor necrosis factor (TNF) dramatically alleviates symptoms, but spinal damage can still be progressive even during anti-TNF treatment. Smoking is a one of well-known risk factors for structural damage in AS. However, it has not been confirmed that smoking can affect radiographic progression even during anti-TNF treatment. To investigate factors associated with radiographic progression during anti-TNF treatment with a focus on smoking status which is known as one of poor prognostic factors for AS. We conducted a retrospective cohort study of AS patients who began the first-line anti-TNF treatment between 2001 and 2018 according to availability of smoking data. All enrolled patients were observed until the last visit, the first-line anti-TNF discontinuation, or December 2019. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The mSASSS progression rate (units/year) was calculated using the baseline mSASSS, the final mSASSS during observation period, and the duration between them. Univariable and multivariable logistic regression analyses were performed to identify associated factors of mSASSS progression rate > 1 unit/year. Among 459 AS patients, 185 (40.3%) patients were never smokers, 62 (13.5%) were ex-smokers and 212 (46.2%) were current smokers at baseline. Ex- and current smokers had higher mSASSS progression rates than never smokers [never smoker 0.1 (0.0-0.7), ex-smoker 0.6 (0.0-1.5), and current smoker 0.6 (0.0-1.5) units/year, P < 0.001]. In the multivariable logistic analysis, current smoking [adjusted odds ratio (OR) 1.69, 95% CI 1.01-2.82, P = 0.047] and higher baseline mSASSS [adjusted OR 1.03, 95% CI 1.01-1.04, P < 0.001] were associated with a mSASSS progression rate > 1 unit/year. Current smoking is a modifiable risk factor for radiographic progression in patients with AS on anti-TNF treatment. Quitting smoking should be strongly recommended.

Which Metrological Index, the BASMI or EDASMI, is Best Correlated with Disease-Related Parameters in Spondylarthritis Patients?

This study aimed at comparing the Edmonton Ankylosing Spondylitis Metrology Index (EDASMI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) to determine which of the two is best correlated with disease-related parameters in axial spondyloarthritis (axSpA) patients. A cross-sectional study was carried out involving 86 patients with radiographic axSpA. Sociodemographic data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire were applied. Spinal mobility was assessed by two indices: the BASMI and the EDASMI. Structural damage of the spine was also evaluated by two indices: the Bath Ankylosing Spondylitis Radiology Index (BASRI) and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Eighty-six patients with an average age of 43.21 ± 11.43 years (20-79) were included. Impaired spinal mobility, which corresponds to higher BASMI scores, was correlated with prolonged disease duration (p < 0.01, r = 0.310), higher ASDAS-CRP (p < 0.001, r = 0.386), severe functional disability on the BASFI (p < 0.01, r = 0.505) and poorer quality of life according to the ASQoL (p < 0.01, r = 0.369). However, the EDASMI score did not correlate with any disease parameter. The BASMI was correlated with the total BASRI (p < 0.01, r = 0.634) and mSASSS (p < 0.01, r = 0.388). Unlike the BASMI, the EDASMI was neither correlated with the BASRI (p = 0.520, r = 0.245) nor the mSASSS (p = 0.252, r = -0.120). Our results indicate that among the studied metrological indices, the BASMI is more contributory since it is correlated with clinical disease parameters and structural damage, unlike the EDASMI.

Role of macrophage-associated chemokines in the assessment of initial axial spondyloarthritis.

To identify biomarkers that reflect disease activity scores and to investigate the role of macrophage-associated chemokines in initial axial spondyloarthritis (axSpA). Patients with axSpA were enrolled. The SpondyloArthritis Research Consortium of Canada (SPARCC) method was used to score bone marrow oedema (BMO) in the inflammatory lesions on magnetic resonance imaging (MRI). Radiographic assessment of the spine was performed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Clinical variables, including inflammatory markers, serum CC chemokine ligand 2 (CCL2), CCL3, CCL7, CCL8 and C-X3-C motif ligand 1 (CX3CL1), were measured. Correlation analysis between serum levels of these macrophage-associated chemokines and clinical data was performed. There were no significant differences between the axSpA group and the healthy control group in terms of serum levels of CCL2, CCL3 or CCL8. Compared to the healthy control group, the serum levels of CCL7 and CX3CL1 were significantly higher in ankylosing spondylitis (AS) (p = 0.045, p = 0.017, respectively). In the AS subgroup, the serum level of CX3CL1 had a positive correlation with SPARCC scores. In AS, serum CCL7 and CX3CL1 levels are elevated. The serum level of CX3CL1 is associated with MRI-determined oedema in AS. CX3CL1 may be useful as a biomarker to predict active inflammation in the sacroiliac joint (SIJ) in AS. Key Points • Serum levels of CX3CL1 are associated with MRI-determined oedema in AS. • CX3CL1 may be a useful biomarker to predict active inflammation in the sacroiliac joint in AS.

Clinical, radiological, and magnetic resonance imaging characteristics of axial spondyloarthritis with late onset.

We aimed to investigate the clinical, diagnostic, and imaging features of patients with late onset axial spondyloarthritis (SpA) with initial symptom manifestation aged over 45 years.Participants with axial SpA were consecutively recruited. Clinical, demographic, blood, and imaging parameters were compared between the groups with early (≤45 years) and late onset (>45 years) at a cross-sectional level. Logistic regressions were used to determine the independent associations with axial SpA with late onset.A total of 455 participants were recruited. Among them, 70 (15.4%) had late onset disease. Multivariate analyses showed that axial SpA with late onset was associated with higher C-reactive protein based ankylosing spondylitis disease activity index (ASDAS-CRP) (B = 0.10; P = .04), higher intensity of spinal inflammation as measured by maximum apparent diffusion coefficient (spinal ADC max) (B = 0.27; P = .03) and mean ADC (spinal ADC mean) (B = 0.30; P = .004), lower modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) (B = –0.12; P = .02), more tender joint count (B = 0.12; P = .02), and fewer inflammatory back pain (IBP) (OR = 0.26; P < .001).Axial SpA with late onset had higher clinical disease activity, higher intensity of spinal MRI inflammation, less radiographic damage, and more tender joint count. There was also less inflammatory back pain, which could make the diagnosis more difficult.

Relationship Between Inflammation and Radiographic Progression in Patients With Ankylosing Spondylitis Attaining a BASDAI of Less Than 4 During Tumor Necrosis Factor Inhibitor Treatment.

To determine the relationship between inflammation and radiographic progression over time in patients with ankylosing spondylitis (AS) attaining a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of < 4 during tumor necrosis factor inhibitor (TNFi) treatment. Medical records data of patients with AS with BASDAI scores of < 4 during TNFi treatment were analyzed at 6-month intervals from January 2001 to December 2018. To determine the relationship between the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and C-reactive protein (CRP) over time, we fitted linear mixed models with mSASSS as the response variable, baseline mSASSS and the cumulative sum of CRP with different lag times (6, 12, 18, 24, 30, and 36 months) as fixed effects, and patients as random effects. Associations between mSASSS and the cumulative sum of CRP, or the lag times with the highest beta coefficients, were further investigated with linear mixed models that included additional clinical variables. A total of 2956 intervals were obtained from 333 patients. Among different lag times, the cumulative sum of log CRP in the previous 18 to 36 months associated with mSASSS showed significant beta coefficients. In the final linear mixed model, the cumulative sum of log CRP in the previous 24 months was significantly associated with mSASSS at 24 months (β 0.04, 95% CI 0.01-0.07, P = 0.004). Remnant inflammation correlates with radiographic progression, even in patients attaining a BASDAI of < 4 during TNFi treatment. CRP is a surrogate marker for radiographic progression despite clinical improvement with TNFi treatment.

Upadacitinib in active ankylosing spondylitis: results of the 2-year, double-blind, placebo-controlled SELECT-AXIS 1 study and open-label extension

IntroductionLong-term safety and efficacy of upadacitinib in patients with active ankylosing spondylitis (AS) has not been previously reported.MethodsIn SELECT-AXIS 1, patients receiving placebo were switched to upadacitinib 15 mg once...

Can whole spine magnetic resonance imaging predict radiographic progression and inflammatory activity in axial spondyloarthritis?

To investigate whether initial whole spine magnetic resonance imaging (MRI) predicts radiographic progression and inflammatory activity in patients with axial spondyloarthritis (axSpA). A retrospective analysis of spine MRI and X-rays from 70 axSpA patients was conducted. The number of affected discovertebral units was determined according to the definition of pathologic lesions on spine MRI set down by the ASAS/OMERACT group. Radiographic progression was defined as an increase in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) of≥2 compared with baseline. The association of spine MRI with radiographic progression, cumulative C-reactive protein (CRP), and cumulative erythrocyte sedimentation rate (ESR) was investigated. The axSpA-relevant lesions on spine MRI at baseline were independent predictors of radiographic progression. Arthritis of the costovertebral and costotransverse joints on MRI showed the highest odds ratio at 3years (OR [95% CI]: 2.54 [1.29-5.02]). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) for radiographic progression at 2years was 0.89 [95% CI: 0.81-0.96] for structural lesions and 0.83 [95% CI: 0.72-0.94] for inflammatory lesions. Notably, subgroup analysis of 26 patients with mSASSS=0 showed that fatty metaplasia on MRI were highly predictive of radiographic progression at 3years (AUC [95% CI]: 0.87 [0.61-1.00]). Moreover, 3-year cumulative ESR and CRP values increased in proportion to the extent of inflammatory lesions on initial MRI. Initial MRI assessment of the whole spine may predict radiographic progression and subsequent systemic inflammatory burden in axSpA patients, particularly those without axSpA-relevant abnormalities on spine X-rays.

Treatment with tumour necrosis factor inhibitors is associated with a time-shifted retardation of radiographic spinal progression in patients with axial spondyloarthritis

ObjectiveThe objective of the current study was to analyse the association between treatment with tumour necrosis factor inhibitors (TNFi) and radiographic spinal progression in patients with axial spondyloarthritis (axSpA) from...

OP0021 TREATMENT WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IS ASSOCIATED WITH RETARDATION OF RADIOGRAPHIC SPINAL PROGRESSION IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: 10-YEAR RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT

BackgroundThere are conflicting data regarding effect of nonsteroidal anti-inflammatory drugs (NSAID) on radiographic spinal progression in axial spondyloarthritis (axSpA). The analysis of the first 2-year of the GErman SPondyloarthritis Inception Cohort (GESPIC) showed that higher NSAID intake may retard new bone formation in r-axSpA. It remained, however, unclear, whether cyclooxygenase-2 selective inhibitors (COX2i) might have a stronger effect than non-selective (NS) ones and if the effect could be observed also in nr-axSpA.ObjectivesTo investigate the effect of NSAIDs (COX2i and NS) intake on radiographic spinal progression in patients with r-axSpA and nr-axSpA.MethodsBased on availability of at least two sets of spinal radiographs during 10-year follow-up, 243 patients with early axSpA (130 and 113 nr- and r-axSpA, respectively) from GESPIC were included in this analysis. The patients contributed a total of 540 2-year radiographic intervals. Radiographs were scored by 3 trained and calibrated readers according to modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Final mSASSS was calculated as a mean of 3 readers, and progression was defined as absolute mSASSS change score over 2 years. NSAID type, daily dose, and frequency of intake were recorded at visits. The ASAS index of NSAID intake (0-100) counting both dose and duration of intake was calculated for intervals. The association between NSAID intake (NSAID type and NSAID score) and radiographic spinal progression over 2 years was analysed using longitudinal generalized estimated equations (GEE).ResultsAt baseline, 161 (66.3%) patients were treated with NSAIDs. While 289 (53.5%) and 128 (23.7%) 2-year radiographic intervals were covered by NS and COX-2i respectively, 123 (22.8%) intervals were not covered by NSAID. The significant association between higher NSAID intake and retardation of radiographic spinal progression was found in adjusted multivariable longitudinal GEE analysis. This effect was mostly attributable to patients with r-axSpA (Table 1). mSASSS progression was numerically lower in patients taking COX2i (irrespectively of dose) as compared to patients treated with NS-NSAIDs; in stratified analysis, however, there was no clear dose-dependency (as reflected by NSAID index) in both groups (Figure 1, Table 1).Table 1.The association between radiographic spinal progression (mSASSS change score) and NSAID intake in patients with axSpA in multivariable longitudinal GEEAll axSpA β (95% CI)* (n=461)nr-axSpA β (95% CI)*(n=244)r-axSpA β (95% CI)* (n=217)NSAID intake score, per 10 points-0.04 (-0.09, 0.00)-0.02 (-0.06, 0.02)-0.07 (-0.13, 0.00)NSAID type§ NS inhibitors vs No NSAID0.30(-0.07, 0.66)0.25(-0.07, 0.57)0.26(-0.40, 0.92) COX2i vs No NSAID0.17(-0.19, 0.54)0.15(-0.15, 0.46)0.18(-0.49, 0.85) COX2i vs NS inhibitors-0.12(-0.37, 0.12)-0.10(-0.28, 0.09)-0.08(-0.57, 0.40)Analysis stratified according to NSAID typeNon-selective NSAID intake score, per 10 points-0.06(-0.12, 0.00)-0.04(-0.09, 0.01)-0.07(-0.17, 0.03)COX2 selective NSAID intake score, per 10 points-0.06(-0.13, 0.02)-0.03(-0.07, 0.02)-0.09(-0.18, 0.01)axSpA: axial spondyloarthritis; COX2i, cyclooxygenase-2 selective inhibitors; n, number of current 2-year radiographic intervals in multivariable analyses; NS, non-selective COXi; NSAID, non-steroidal anti-inflammatory drugs.*All multivariable models were adjusted for sex, symptom duration at the beginning of the interval, time-averaged ASDAS the interval, classification as radiographic axSpA, smoking in the interval, mSASSS at the beginning of theinterval, and TNFi use in the interval.§NSAID intake score was added in this model.ConclusionHigher NSAID intake is associated with lower radiographic spinal progression, particularly in r-axSpA patients. COX2i might possess a stronger inhibitory effect on radiographic progression as compared to NS-NSAIDs.Disclosure of InterestsMurat Torgutalp: None declared, Valeria Rios Rodriguez Consultant of: AbbVie, Grant/research support from: Falk e.V, Ani Dilbaryan: None declared, Fabian Proft Speakers bureau: Novartis, Lilly, UCB AbbVie, AMGEN, BMS, Hexal, MSD, Pfizer, Roche and Janssen, Grant/research support from: Novartis, Lilly and UCB, Mikhail Protopopov Consultant of: Novartis and UCB, Maryna Verba: None declared, Judith Rademacher Consultant of: Novartis and UCB, Hildrun Haibel Consultant of: Boehringer, Janssen, MSD, Novartis, Sobi, Roche, Pfizer, AbbVie, and Sobi, Joachim Sieper Speakers bureau: Abbvie, Janssen, Lilly, Merck, Novartis, UCB, Consultant of: AbbVie, Lilly, Merck, Novartis, UCB, Martin Rudwaleit Speakers bureau: AbbVie, Boehringer Ingelheim, Celgen, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB., Consultant of: AbbVie, Boehringer Ingelheim, Celgen, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB., Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer.

OP0018 COMPARISON OF THE EFFECT OF TREATMENT WITH NSAIDs ADDED TO ANTI-TNF THERAPY VERSUS ANTI-TNF THERAPY ALONE ON PROGRESSION OF STRUCTURAL DAMAGE IN THE SPINE OVER TWO YEARS IN PATIENTS WITH ANKYLOSING SPONDYLITIS (CONSUL) – AN OPEN-LABEL, RANDOMIZED CONTROLLED, MULTICENTER TRIAL

BackgroundThere is some evidence that NSAIDs, in particular celecoxib (CEL), might possess not only symptomatic efficacy but also disease-modifying properties in radiographic axial spondyloarthritis (r-axSpA) formerly known as ankylosing spondylitis, retarding progression of structural damage in the spine if taken continuously. For biological disease-modifying antirheumatic drugs (bDMARDs), retardation of structural damage progression has also been demonstrated, but at least 4 years of treatment seem to be necessary (at least for tumour necrosis factor inhibitors – TNFi) to see such an effect. Therefore, a combination of an NSAID with a TNFi might bring additional benefits in terms of retardation of structural damage progression especially in high-risk patients.ObjectivesThe aim of this RCT was to evaluate the impact of treatment with the COX-II-selective NSAID (CEL) when added to a TNFi (golimumab - GOL) compared with TNFi (GOL) alone on progression of structural damage in the spine over 2 years in patients with r-axSpA.MethodsEligible patients had r-axSpA and high disease activity (BASDAI ≥4), NSAID failure and risk factors for radiographic spinal progression: C-reactive protein &gt;5 mg/l and/or ≥1 syndesmophyte(s). The trial consisted of two phases: a 12-week run-in phase, in which all included patients received treatment with GOL 50 mg every 4 weeks sc, followed by a 96-week controlled treatment period, in which patients who achieved a BASDAI improvement of ≥2 points were randomly assigned to GOL + CEL 200 mg bid or GOL alone arms. The primary endpoint was radiographic spinal progression as assessed by the change in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) after 108 weeks in the intent-to-treat population, read by 3 independent readers blinded for the treatment arm and the time-point.ResultsOf the 157 screened patients, 81.5% (n=128) were enrolled into the run-in phase. 109 patients fulfilled the BASDAI response criterion at w12 and were randomized 1:1 (54 vs. 55) to GOL+CEL or GOL alone; 97 (45 vs. 52) patients completed the study at w108. Clinical characteristics of the randomized patients are shown in Tab. 1. The mSASSS change after w108 was 1.1 (95%CI 0.2; 2.0) vs. 1.7 (95%CI 0.8; 2.6) in the GOL+CEL vs. GOL alone groups, respectively, p=0.79. Figure 1 shows the cumulative probability of the mSASSS change in both treatment arms. New syndesmophytes in the opinion of three readers occurred in 11% vs. 25% of the patients in the GOL+CEL vs. GOL alone groups, respectively, p=0.12. During the study, a total of 14 serious adverse events (SAE) were reported (7 in the GOL+CEL group, 5 in the GOL alone group and 2 during the run-in phase).Figure 1.Cumulative probability plot of mSASSS progression over 108 weeks of treatment.ConclusionIn this study, a combined therapy with GOL+CEL did not show significant superiority over GOL monotherapy in retarding radiographic spinal progression over two years in r-axSpA patients.However, the observed numerical reduction in radiographic spinal progression associated with the combined treatment might be, however, clinically relevant for patients at high risk for progression.Table 1.Baseline characteristics of randomized patientsParametersGOL+CEL N=54GOL alone N=55All patients N=109validnvaluevalidnvaluevalidnvalueSex, malen (%)5440 (74.1)5541 (74.5)10981 (74.3)Age, yearsMean (SD)5439.9 (9.9)5537.5 (10.8)10938.7 (10.4)Smokern (%)5319 (35.8)5522 (40)10841 (38)HLA-B27 positivityn (%)5445 (83.3)5147 (92.2)10592 (87.6)BASDAIMean (SD)546.2 (1)556.1 (1.1)1096.1 (1.1)BASMIMean (SD)542.6 (1.9)542.9 (1.4)1082.8 (1.6)CRP &gt; 5 mg/Ln (%)5438 (70.4)5538 (69.1)10976 (69.7)ASDAS-CRPMean (SD)543.6 (0.6)553.7 (0.9)1093.7 (0.8)Prior bDMARDsn (%)5417 (31.5)559 (16.4)10926 (23.9)Presence of ≥ 1 syndesmophyte(s)n (%)5427 (50)5528 (50.9)10955 (50.5)mSASSSMean (SD)5413.5 (16.9)5510.3 (13.2)10911.9 (15.2)AcknowledgementsThe CONSUL study has been supported by a grant from the German Ministry of Education and Research (BMBF), grant number FKZ 01KG1603 and study medication (golimumab) was provided free of charge by MSD Sharp &amp; Dohme GmbH, Munich, Germany.Furthermore we would like to thank Anne Weber, Bianca Mandt, Claudia Lorenz, Hildrun Haibel, Judith Rademacher, Laura Spiller, Petra Tietz as well as all participating rheumatologist and included patients.Disclosure of InterestsFabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, UCB, Lilly, Burkhard Muche Speakers bureau: UCB Pharma, AMGEN, Consultant of: UCB Pharma, AMGEN, Valeria Rios Rodriguez Speakers bureau: AbbVie, Falk e.V., Murat Torgutalp: None declared, Mikhail Protopopov Consultant of: Novartis, Joachim Listing: None declared, Maryna Verba: None declared, Uta Kiltz: None declared, Jan Brandt-Juergens: None declared, Maren Sieburg: None declared, Swen Holger Jacki: None declared, Joachim Sieper Speakers bureau: AbbVie, Janssen, Merck, Novartis, Consultant of: Abbvie, Janssen, Lilly, Merck, Novartis, UCB, Denis Poddubnyy Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, and Pfizer.

The roles of Single Nucleotide Polymorphism (SNP) Endoplasmic Reticulum Aminopeptidase 1 (ERAP 1) gene in axial spondyloarthritis Indonesian adults

BackgroundAxial Spondyloarthritis (AxSpA) is chronic inflammatory arthritis involving the axial joint whose pathogenesis is related to the SNP ERAP1 gene, HLA B27, and cytokine proinflammatory (IL-17A and IL-23). ObjectiveAnalyzed the role of SNP gene ERAP1 on disease activity and proinflammatory cytokines. MethodsThis study comprised of two phases including a cross-sectional study and an in-vitro experiment in post-test with a control-group design. Participants underwent a PCR investigation searching for HLA-B27. Disease activities were measured by Ankylosing Spondylitis Disease Activity Score-Erythrocyte Sedimentation Rate (ASDAS-ESR) and modified Stokes Ankylosing Spondylitis Spinal Score (mSASSS). Subjects with HLA-B27 positive underwent PCR ERAP1 gene rs27434, genome-sequencing, and analysis. ELISA sandwich method was used to measure ERAP-1, IL-17, and IL-23 levels with lipopolysaccharide and IFN-γ induction. Analysis using independent t-test, Mann Whitney, and Pearson correlation test with p < 0.05. ResultsThe average ASDAS-ESR was 3.33 ± 0.89 and the average mSASSS was 26.53 ± 9.90. In HLA B27 positive group, SNP ERAP1 gene rs 27434 in which alleles A changed to G and A/G with genotypes AA to AG/GG was observed. SNPs of the ERAP1 gene had a correlation on mSASSS (r = 0.553; p < 0.05) and no correlation on ASDAS-ESR (r = 0.232; p = 0.235). There were significant differences observed in the SNP ERAP1 gene on ERAP1 and IL-17A levels in subjects with lipopolysaccharide and IFN-γ induction (p = 0.05) but no significant difference in IL-23 levels (p > 0.05). ConclusionThe SNP ERAP1 gene affects mSASSS value, ERAP1 levels, and IL-17A levels whereas ASDAS-ESR value and IL-23 level were not associated.