Radiographic Spinal Progression In Patients Research Articles

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.

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...

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.

Early control of C-reactive protein levels with non-biologics is associated with slow radiographic progression in radiographic axial spondyloarthritis.

Predicting radiographic progression is vital for assessing the prognosis of patients with radiographic axial spondyloarthritis, and C-reactive protein (CRP) may be a valuable biomarker for this purpose. This study aimed to investigate the relationship between changes in the CRP level and spinal radiographic progression in patients with radiographic axial spondyloarthritis who were initially treated with non-biologics. Patients with radiographic axial spondyloarthritis who were followed up for 18years at a single center and initially treated with nonsteroidal anti-inflammatory drugs and/or conventional disease-modifying antirheumatic drugs for 3months were included. Patients with a CRP level of <0.8mg/dL or 50% of the baseline CRP at 3months were assigned to the controlled CRP group (n=351), and the remaining patients were assigned to the uncontrolled CRP group (n=452). A generalized estimating equation was used to analyze the differences in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between the 2 groups. The increase in the mSASSS was slower in the controlled CRP group than in the uncontrolled CRP group (interaction term β=-.499, 95% confidence interval -0.699 to -0.300). Controlled CRP achieved in response to initial treatment with non-biologic agents for 3months was significantly associated with a slower rate of spinal radiographic change in patients with radiographic axial spondyloarthritis. The CRP level at 3months after initial non-biologic treatment is a good predictor of radiographic progression.

Tumor Necrosis Factor Inhibitors Reduce Spinal Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: A Longitudinal Analysis From the Alberta Prospective Cohort.

ObjectiveTo investigate whether tumor necrosis factor inhibitors (TNFi) impact spinal radiographic progression in patients with axial spondyloarthritis (SpA) and whether this is coupled to their effect on inflammation.MethodsPatients with axial SpA fulfilling the modified New York criteria were included in a prospective cohort (the ALBERTA Follow Up Research Cohort in Ankylosing Spondylitis Treatment). Spine radiographs, performed every 2 years for up to 10 years, were scored by 2 central readers, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The indirect effect of TNFi on mSASSS was evaluated with generalized estimating equations by testing the interaction between TNFi and Ankylosing Spondylitis Disease Activity Score (ASDAS) at the start of each 2‐year interval (t). If significant, the association between ASDAS at t and mSASSS at the end of the interval (t+1) was assessed in 1) patients treated with TNFi at all visits, 2) patients treated with TNFi at some visits, and 3) patients who were never treated with TNFi. In addition, the association between TNFi at t and mSASSS at t+1 (adjusting for ASDAS at t) was also tested (direct effect).ResultsIn total, 314 patients were included. A gradient was seen for the effect of ASDAS at t on mSASSS at t+1 (interaction P = 0.10), with a higher progression in patients never treated with TNFi (β = 0.41 [95% confidence interval (95% CI) 0.13, 0.68]) compared to those continuously treated (β = 0.16 [95% CI 0.00, 0.31]) (indirect effect). However, TNFi also directly slowed progression, as treated patients had on average an mSASSS 0.85 units lower at t+1 compared to untreated patients (β = −0.85 [95% CI −1.35, −0.35]).ConclusionOur findings indicate that TNFi reduce spinal radiographic progression in patients with radiographic axial SpA, which might be partially uncoupled from their effects on inflammation as measured by the ASDAS.

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review.

We aimed to perform a structured literature review of spinal radiographic progression, as assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), in patients with ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) treated with biologic therapy. Searches were limited to English language manuscripts published in the 11 years prior to 9 July 2019. Randomized controlled trials, open-label extensions (OLEs) and observational studies reporting mSASSS progression in patients with AS or nr-axSpA treated with biologics were eligible for inclusion. Bias was assessed using the methodological index for nonrandomized studies (MINORS) tool. Among the 322 studies identified in the literature search, 23 (11 OLEs and 12 cohort studies) met the eligibility criteria and were selected for inclusion. Most studies reported mSASSS progression in patients with AS receiving tumor necrosis factor inhibitor (TNFi) treatment. One study reported mSASSS progression in patients with AS treated with secukinumab, an interleukin-17A inhibitor. The mean (range) MINORS score was 11.3 (7–15) for the 15 noncomparative studies and 15 (12–22) for the 8 comparative studies. Although results of the individual studies were variable, mSASSS progression in patients with AS was generally minimal and slow with long-term TNFi therapy. Moreover, odds ratios for the likelihood of mSASSS progression with/without TNFi favoured TNFi therapy in several of the cohort studies. The rate of mSASSS progression following continuous secukinumab treatment was low and remained stable over 4 years. Of two studies reporting progression in patients with nr-axSpA treated with TNFis, one showed no mSASSS progression; however, the lack of control limited comparative conclusions.

Low bone mineral density of vertebral lateral projections can predict spinal radiographic damage in patients with ankylosing spondylitis.

To investigate the association between bone mineral status and spinal radiographic damage in patients with ankylosing spondylitis (AS) and determine whether bone mineral status can predict further spinal radiographic damage after 2years. Bone mineral density (BMD) of the lumbar spine (anteroposterior and lateral projections), femoral neck, and total hip and trabecular bone score (TBS) of the lumbar spine were measured in AS patients (n = 54) who fulfilled the modified New York criteria. Spinal radiographic damage was scored on cervical and lumbar spine radiographs using modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline and after 2years. Simple and multiple linear regression analyses were performed to examine predictors of spinal radiographic damage. Patients with advanced AS exhibited low BMD on lumbar spine lateral projections, femoral neck, and total hip and low TBS. Low vertebral bone mass at baseline, assessed by BMD of the lateral projections or TBS, was independently associated with baseline mSASSS. After 2years, mSASSS change from baseline was significantly associated with high baseline mSASSS, high baseline erythrocyte sedimentation rate and C-reactive protein (CRP) levels, and low baseline BMD of the lumbar spine lateral projections. The best predictive model for spinal radiographic progression consisted of baseline mSASSS, baseline CRP, and low BMD of lateral lumbar spine (area under curve = 0.826). BMD at vertebral lateral projections and TBS were inversely associated with baseline mSASSS in AS patients. Low BMD at vertebral lateral projections, as well as baseline mSASSS and inflammatory markers, might predict spinal radiographic damage in AS.Key Points• Vertebral bone mineral density of lateral projections and trabecular bone score are inversely associated with baseline mSASSS in patients with ankylosing spondylitis.• Baseline mSASSS, inflammatory markers, and low vertebral bone mineral density might predict spinal radiographic progression in patients with ankylosing spondylitis.

Incorporation of the anteroposterior lumbar radiographs in the modified Stoke Ankylosing Spondylitis Spine Score improves detection of radiographic spinal progression in axial spondyloarthritis

BackgroundTo evaluate the performance of the extended modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) incorporating information from anteroposterior (AP) lumbar radiographs as compared to the conventional mSASSS in detection of radiographic spinal progression in patients with axial spondyloarthritis (axSpA)MethodsA total of 210 patients with axSpA, 115 with radiographic axSpA (r-axSpA), and 95 with non-radiographic axSpA (nr-axSpA), from the GErman SPondyloarthritis Inception Cohort (GESPIC), were included in the analysis based on the availability of spinal radiographs (cervical spine lateral, lumbar spine lateral, and AP views), at baseline and year 2. Two trained readers independently scored lateral cervical and lumbar spine images according to the mSASSS system (0–3 per vertebral corner, 0–72 in total). In addition, all vertebral corners of vertebral bodies visible on lumbar AP radiographs (lower T12 to upper S1) were assessed according to the same scoring system that resulted in a total range for the extended mSASSS from 0 to 144. Reliability and sensitivity to detect radiographic spinal progression of the extended mSASSS as compared to the conventional mSASSS were evaluated.ResultsThe reliability of conventional and extended scores was excellent with intraclass correlation coefficients (ICCs) of 0.926 and 0.927 at baseline and 0.920 and 0.933 at year 2, respectively. The mean ± SD score for mSASSS and extended mSASSS at baseline were 4.25 ± 8.32 and 8.59 ± 17.96, respectively. The change score between baseline and year 2 was 0.73 ± 2.34 and 1.19 ± 3.73 for mSASSS and extended mSASSS, respectively. With the extended mSASSS, new syndesmophytes after 2 years were detected in 4 additional patients, new syndesmophytes or growth of existing syndesmophytes in 5 additional patients, and progression by ≥ 2 points in the total score in 14 additional patients meaning a 25%, 28%, and 46% increase in the proportion of patients with progression according to the respective definition as compared to the conventional score.ConclusionsIncorporation of lumbar AP radiographs in the assessment of structural damage in the spine resulted into detection of additional patients with radiographic spinal progression not captured by the conventional mSASSS score.

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.

Effect of tumor necrosis factor α inhibitors on spinal radiographic progression in patients with ankylosing spondylitis.

To evaluate the effect of tumor necrosis factor α inhibitors (TNFi) on spinal radiographic progression in patients with ankylosing spondylitis (AS). Subjects were selected from patients at a single tertiary hospital between 1995 and 2014. Patients who used TNFi with baseline and paired follow-up radiographic data with a minimum interval of 2years were included. Time to start TNFi was defined as the time from symptom onset to the start of TNFi use. TNFi index was defined as the ratio of the period of TNFi use to the entire period of disease. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Univariable and multivariable linear regression analyses were used to identify factors associated with radiographic progression. A total of 151 patients were included in the analysis. Seventeen (11.3%) patients were female and mean ΔmSASSS/year was 1.01 units/year. Mean X-ray follow-up duration was 102.9±54.9months. Mean time from symptom onset to start of TNFi use was 104.8±83.6months (median 84months) and mean TNFi index was 42.9±23.8% (median 40.9%). In multivariable analysis, initial mSASSS, initial C-reactive protein, body mass index, current smoker, and delayed start of TNFi use were associated with radiographic progression. Presence of peripheral arthritis and the TNFi index were negatively associated with radiographic progression. A delay in starting TNFi use and low TNFi index were associated with radiographic progression. Early and long-term use of TNFi appear to reduce spinal radiographic progression in patients with AS.

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...

Serum levels of leptin and high molecular weight adiponectin are inversely associated with radiographic spinal progression in patients with ankylosing spondylitis: results from the ENRADAS trial

BackgroundPrevious research indicates a role of adipokines in inflammation and osteogenesis. Hence adipokines might also have a pathophysiological role in inflammation and new bone formation in patients with ankylosing spondylitis (AS). The aim of this study was to investigate the role of adipokine serum levels as predictors of radiographic spinal progression in patients with AS.MethodsA total of 120 patients with definite AS who completed a 2-year follow up in the ENRADAS trial were included in the current study. Radiographic spinal progression was defined as: (1) worsening of the modified Stoke Ankylosing Spondylitis spine (mSASSS) score by ≥2 points and/or (2) new syndesmophyte formation or progression of existing syndesmophytes after 2 years. Serum levels of adipokines (adiponectin (APN) and its high molecular weight form (HMW-APN), chemerin, leptin, lipocalin-2, omentin, resistin, visfatin) were measured using enzyme-linked immunosorbent assays.ResultsThere was a significant association between radiographic spinal progression and both leptin and HMW-APN. Baseline serum levels of both adipokines were lower in patients who showed radiographic spinal progression after 2 years. This association was especially evident in men; they had generally lower leptin and HMW-APN serum levels as compared to women. The inverse association between adipokines and radiographic spinal progression was confirmed in the logistic regression analysis: the odds ratios (OR) for the outcome “no mSASSS progression ≥2 points” were 1.16 (95% CI 1.03 to 1.29) and 1.17 (95% CI 0.99 to 1.38), for leptin and HMW-APN, respectively; for “no syndesmophyte formation/progression” the respective OR were 1.29 (95% CI 1.11 to 1.50) and 1.18 (95% CI 0.98 to 1.42), adjusted for the presence of syndesmophytes at baseline, C-reactive protein at baseline, sex, body mass index (BMI), non-steroidal anti-inflammatory drugs intake score over 2 years, and smoking status at baseline.ConclusionSerum leptin and HMW-APN predict protection from spinal radiographic progression in patients with AS. Women generally have higher leptin and HMW-APN serum levels that might explain why they have less structural damage in the spine as compared to male patients with AS.Trial registrationEudraCT: 2007-007637-39. ClinicalTrials.gov, NCT00715091. Registered on 14 July 2008.

Physical Function and Spinal Mobility Remain Stable Despite Radiographic Spinal Progression in Patients with Ankylosing Spondylitis Treated with TNF-α Inhibitors for Up to 10 Years.

The aim of the study was to investigate the effect of radiographic spinal progression and disease activity on function and spinal mobility in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor-α (TNF-α) inhibitors for up to 10 years. Patients with AS who participated in 2 longterm open-label extensions of clinical trials with TNF-α inhibitors (43 receiving infliximab and 17 receiving etanercept) were included in this analysis based on the availability of spinal radiographs performed at baseline and at a later timepoint (yr 2, 4, 6, 8, and 10) during followup. Spinal radiographs were scored according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Function was assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI), spinal mobility by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and disease activity by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). After the initial improvement, BASFI and BASMI remained remarkably stable at low levels over up to 10 years despite radiographic spinal progression. In the generalized mixed effects model analysis, no association between the mSASSS and the BASFI change (β = 0.0, 95% CI -0.03 to 0.03) was found, while there was some effect of mSASSS changes on BASMI changes over time (β = 0.05, 95% CI 0.01-0.09). BASDAI showed a strong association with function (β = 0.64, 95% CI 0.54-0.73) and to a lesser extent, with spinal mobility (β = 0.14, 95% CI 0.01-0.26). Functional status and spinal mobility of patients with established AS remained stable during longterm anti-TNF-α therapy despite radiographic progression. This indicates that reduction and continuous control of inflammation might be able to outweigh the functional effect of structural damage progression in AS.

High disease activity according to the Ankylosing Spondylitis Disease Activity Score is associated with accelerated radiographic spinal progression in patients with early axial spondyloarthritis: results from the GErman SPondyloarthritis Inception Cohort

ObjectiveThe aim of this work was to investigate the association between disease activity measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and radiographic spinal progression in patients with early...

Fat Metaplasia on Sacroiliac Joint Magnetic Resonance Imaging at Baseline Is Associated with Spinal Radiographic Progression in Patients with Axial Spondyloarthritis.

ObjectiveTo study the relationship between inflammatory and structural lesions in the sacroiliac joints (SIJs) on MRI and spinal progression observed on conventional radiographs in patients with axial spondyloarthritis (axSpA).MethodsOne hundred and ten patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI at baseline and lumbar spine radiographs at baseline and after 2 years. Inflammatory and structural lesions on SIJ MRI were scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Multivariate logistic regression analysis was performed to identify predictors of spinal progression.ResultsAmong the 110 patients, 25 (23%) showed significant radiographic progression (change of SASSS≥2) over 2 years. There was no change in the SASSS over 2 years according to the type of inflammatory lesion. Patients with fat metaplasia or ankyloses on baseline MRI showed a significantly higher SASSS at 2 years than those without (p<0.001). According to univariate logistic regression analysis, age at diagnosis, HLA-B27 positivity, the presence of fat metaplasia, erosion, and ankyloses on SIJ MRI, increased baseline CRP levels, and the presence of syndesmophytes at baseline were associated with spinal progression over 2 years. Multivariate analysis identified syndesmophytes and severe fat metaplasia on baseline SIJ MRI as predictive of spinal radiographic progression (OR, 14.74 and 5.66, respectively).ConclusionInflammatory lesions in the SIJs on baseline MRI were not associated with spinal radiographic progression. However, fat metaplasia at baseline was significantly associated with spinal progression after 2 years.

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.

Serum adipokine levels in patients with ankylosing spondylitis and their relationship to clinical parameters and radiographic spinal progression.

Adipokines have metabolic and inflammatory functions but can also affect bone metabolism. The purpose of this study was to determine the relationship between serum levels of adiponectin, resistin, and visfatin and markers of inflammation, disease activity, and radiographic spinal progression in patients with ankylosing spondylitis (AS). Levels of adiponectin, resistin, and visfatin in the serum of 86 AS patients and 25 healthy controls were measured by enzyme-linked immunosorbent assay at baseline. Radiographic spinal progression was determined by the scoring of radiographs of the spine obtained at baseline and after 2 years. Mean (±SD) baseline levels of resistin and visfatin were significantly higher in AS patients than in healthy controls (11.6 ± 10.6 ng/ml versus 6.6 ± 3.2 ng/ml [P = 0.01] for resistin, and 20.9 ± 48.3 ng/ml versus 3.4 ± 2.6 ng/ml [P = 0.001] for visfatin). Adipokine serum levels did not correlate with disease activity or functional indices. Only resistin serum levels correlated with markers of inflammation. Baseline levels of visfatin, but not resistin or adiponectin, were significantly higher in patients with worsening of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by ≥2 units after 2 years (n = 19) as compared to patients without mSASSS worsening (37.7 ± 57.8 ng/ml versus 16.1 ± 44.6 ng/ml; P = 0.029) and in patients with syndesmophyte formation/progression (n = 22) as compared to patients without such progression (37.1 ± 55.3 ng/ml versus 15.3 ± 44.8 ng/ml; P = 0.023). Visfatin levels of >8 ng/ml at baseline were predictive of subsequent radiographic spinal progression (adjusted odds ratio 3.6 for mSASSS progression and 5.4 for syndesmophyte formation/progression). Serum levels of resistin and visfatin are elevated in AS patients. Elevated visfatin levels at baseline are predictive of subsequent progression of radiographic damage in AS patients.

FRI0113 Persistently High Disease Activity According to the ASDAS is Associated with Accelerated Radiographic Spinal Progression in Patients with Axial Spondyloarthritis

MethodsAltogether 177 patients with definite axial SpA (100 with ankylosing spondylitis (AS) and 77 with non-radiographic axial SpA) from the German Spondyloarthritis Inception Cohort (GESPIC) were included in the current...

SAT0559 High Expression of Cyclooxygenase-2, Prostaglandin E2 and Prostaglandin E2 Receptor Ep4 in Zygapophyseal Joints of Patients with Ankylosing Spondylitis

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for patients with ankylosing spondylitis (AS). They are effective in reducing signs and symptoms, and increasing evidence suggests that their sustained use...