mSASSS Change Research Articles

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...

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

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...

Re-stooping after Corrective Osteotomy in Patients with Ankylosing Spondylitis.

Corrective osteotomy is an effective surgery for correcting posture in patients with ankylosing spondylitis (AS). Despite satisfactory correction, some patients experience re-stooping during follow-up. However, there have been no studies on re-stooping in AS. We aimed to analyze the factors that affect re-stooping. Fifty patients (50 cases) who underwent thoracolumbar corrective osteotomy for AS from March 2006 to April 2018 were analyzed. We defined re-stooping as global kyphosis that recurs after corrective osteotomy. The patients were divided into two groups based on the ratio of correction loss: non-re-stooping group (N group) and re-stooping group (R group). We analyzed the demographic data and radiological parameters, such as modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), sagittal vertical axis, and various angles. We also investigated the factors affecting re-stooping by analyzing the correlation between the ratio of correction loss and various factors. A significant difference was seen in the change in the mSASSS from before surgery to the last follow-up between the N group (2.87 ± 3.08) and the R group (9.20 ± 5.44). In multivariate analysis, only the change in the mSASSS from before surgery to the last follow-up was significantly correlated with the ratio of correction loss. Thoracolumbar corrective osteotomy seems to provide high satisfaction among patients with AS but can lead to re-stooping during follow-up. The change in mSASSS was related with re-stooping in the current study. We recommend active rehabilitative exercises and appropriate medication depending on the patient's condition, which may help delay the postoperative progression of AS.

Age-stratified trends in the progression of spinal radiographic damage in patients with ankylosing spondylitis: a longitudinal study.

Objective:The objective of this study was to investigate spinal radiographic progression in specific age ranges of ankylosing spondylitis (AS) patients.Methods:Longitudinal data for 1125 AS patients at a single hospital from 2000 to 2018 were retrospectively reviewed. Radiographic intervals were obtained from patients with consecutive spinal radiographs. The radiographic progression rate was defined as the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change per year within each interval. Using generalized estimating equations (GEEs), estimated marginal means were calculated for the mSASSS progression rate across age groups after adjusting for potential confounders.Results:We obtained 4016 radiographic intervals and stratified them into five groups based on patient age at the interval start: <20 (n = 122); 20–29 (n = 1124); 30–39 (n = 1690); 40–49 (n = 794); and ⩾50 years (n = 286). The mean (SD) mSASSS progression rate for all the intervals was 0.8 (1.9). The GEE-estimated mean mSASSS progression rate increased with age, peaking in the 30–39 age group with a value of 1.15 [95% confidence interval (CI) 1.03, 1.27], and decreased slightly thereafter. In the presence of risk factors, rapid progression occurred at earlier ages: the GEE-estimated mean mSASSS progression rate in those with elevated C-reactive protein levels and preexisting syndesmophytes was 2.82 (95% CI 1.93, 3.71) in the 20–29 age group.Conclusion:Spinal structural damage in AS seems to progress most rapidly when patients are age 30–39 years. An awareness of the trends in radiographic progression with advancing age could improve understanding of the natural course of AS.

Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years.

To evaluate the long-term effect of ixekizumab (IXE) on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from baseline through 2 years in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), and to identify potential predictors of progression. This study evaluates patients from COAST-V (ClinicalTrials.gov: NCT02696785, biologic disease-modifying antirheumatic drug-naïve) and COAST-W (NCT02696798, tumor necrosis factor inhibitor-experienced) who had mSASSS data at baseline in the originating studies and 108 weeks after baseline in the extension study COAST-Y (NCT03129100). We examined the proportion of patients who did not have spinal radiographic progression through 2 years (108 weeks) of treatment with IXE (80 mg every 2 or 4 weeks) and the change from baseline to year 2 in mSASSS. Potential predictors of spinal radiographic progression were also evaluated. Among patients with evaluable radiographs who were originally assigned to IXE (n = 230), mean (SD) change in mSASSS from baseline at year 2 was 0.3 (1.8). The proportion of nonprogressors over 2 years was 89.6% if defined as mSASSS change from baseline < 2 and 75.7% if defined as mSASSS change from baseline ≤ 0. Predictors of structural progression at year 2 (mSASSS change > 0) were age ≥ 40, baseline syndesmophytes, HLA-B27 positivity, and male sex. Week 52 inflammation in Spondyloarthritis Research Consortium of Canada spine was also a predictor of radiographic progression at year 2 in patients with magnetic resonance imaging data in COAST-V (n = 109). The majority of patients with r-axSpA receiving IXE had no radiographic progression in the spine through 2 years of treatment. Predictors were generally consistent with previous studies.

Effects of secukinumab on bone mineral density and bone turnover biomarkers in patients with ankylosing spondylitis: 2-year data from a phase 3 study, MEASURE 1

BackgroundAxial spondyloarthritis including ankylosing spondylitis (AS) is characterized by chronic inflammation and new bone formation in the axial skeleton. On the other hand, bone loss, osteoporosis and an increased risk of vertebral fractures is known to frequently occur in AS. In the MEASURE 1 study, the clinically efficacious interleukin-17A inhibitor secukinumab was shown to have limited radiographic progression through 4 years in patients with active AS. Here we present a post hoc analysis to evaluate the effect of secukinumab on bone mineral density (BMD) and bone turnover biomarkers over 2 years in this study.MethodsBMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. Spinal radiographs performed at baseline and Week 104 were assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and analyzed in relation to BMD change, considering baseline syndesmophytes. Bone turnover biomarkers were assessed at baseline and at Weeks 52 or 104.ResultsAmong 104 patients included in this analysis, 66% were male, with a mean (SD) age of 40.4 (12.3) years. In postmenopausal women and men ≥50 years of age (T-score), the proportion of patients having normal BMD at baseline and Week 104 were 54.5%/54.5% (lumbar spine), 31.6%/55.6% (total hip), and 42.1%/44.4% (femoral neck). Similarly, at baseline, the proportion of patients with osteopenia/osteoporosis was 31.8%/13.6% (lumbar spine), 57.9%/10.5% (total hip), 42.1%/15.8% (femoral neck), and 36.4%/9.1% (lumbar spine), 44.4%/0% (total hip) and 55.6%/0% (femoral neck) at Week 104, respectively. In premenopausal women and men < 50 years of age (Z-score), the proportion of patients having BMD below the expected range for age at baseline and Week 104 were 25.0%/21.2% (lumbar spine), 11.3%/17.8% (total hip), and 9.9%/8.9% (femoral neck). In relation to mSASSS change scores ≥2 over 2 years, the increase in lumbar spine BMD was not related to radiographic progression and syndesmophyte formation. No significant changes were observed in the bone turnover markers over time.ConclusionThe high proportion of AS patients with diminished BMD was confirmed in this study. An increase of BMD in the lumbar spine after 2 years of secukinumab treatment in patients with AS was found that was probably unrelated to radiographic progression. No relevant effects of secukinumab on bone turnover biomarkers were documented.Trial registrationMEASURE 1 (post hoc analysis) Clinicaltrials.gov, NCT01358175; Registered, 23 May 2011.

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.

Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence

ObjectivesTumour necrosis factor inhibitors (TNFis) have been suggested to slow radiographic progression in patients with ankylosing spondylitis. However, limitations such as variations in disease activity, complex drug administration and short...

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.

Radiographic Progression in Patients With Ankylosing Spondylitis According to Uveitis Based on the Observation Study of Korean Spondyloarthropathy Registry.

This study aims to investigate radiographic progression according to the presence or absence of uveitis in patients with ankylosing spondylitis (AS). A total of 598 patients (529 males, 69 females, mean age 38.1±9.2 years; range, 18 to 73 years) from the Observation Study of Korean Spondyloarthropathy Registry who met the modified New York criteria for AS were included in this study. At baseline, all data were stratified into two groups according to the presence or absence of uveitis. Baseline and radiographic progression were assessed for five years in this registry. Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was read by two radiologists. Reliability was assessed using inter- and intra- class correlation coefficient for each radiograph. Comparison of mSASSS changes was analyzed by analysis of covariance model after adjusting for confounding factors. The evaluation of mSASSS showed good agreement between the two readers. A total of 193 patients (32.27%) had a history of uveitis that presented at a mean age of 39.6 years, including 30 females (15.54%). There were statistically significant differences in age (p=0.01), sex (p=0.04), hip joint involvement (p<0.01), and human leukocyte antigen B27 carrier state (p=0.02) between the two groups according to uveitis. A simple comparison revealed no significant difference in mSASSS change for five years between the two groups (mean: 3.05±0.62 vs. 3.78±0.78, p=0.47). After adjusting for confounding factors in multiple comparisons by Bonferroni correction, patients with uveitis had no significant association with mSASSS change for five years (mean: 6.29±1.32 vs. 5.49±1.39, p=0.68). Our study confirms that there is no significant association between uveitis and radiographic progression in patients with AS after adjusting for confounding factors.

Conventional disease-modifying antirheumatic drugs therapy may not slow spinal radiographic progression in ankylosing spondylitis: results from an 18-year longitudinal dataset.

Objectives:The clinical benefit of conventional disease-modifying antirheumatic drugs (cDMARDs) for treating ankylosing spondylitis (AS) is generally limited to improvements in peripheral arthritis. However, cDMARDs could be conditionally considered as alternatives to established drugs for improving axial manifestations in exceptional circumstances. However, there are few studies of the impact of cDMARDs on radiographic progression outcomes. Therefore, we investigated the effectiveness of cDMARDs on radiographic progression in AS.Methods:Among 1280 AS patients at a single hospital from 2000 to 2018, 301 who had been treated with sulfasalazine (SSZ) or methotrexate (MTX) were enrolled. For each patient, the entire follow-up period was split into 1-year intervals. Each interval was classified as either an “on-cDMARD” interval, which was a period of treatment with SSZ alone, MTX alone, or a combination of SSZ and MTX, or an “off-cDMARD” interval, which was a period without cDMARD treatment. Radiographic progression was scored using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The relationship between cDMARD use and radiographic progression within the intervals, defined as the rate of mSASSS progression, was investigated using linear models with adjustment for potential confounding covariates and for clustering among observations from the same patient.Results:The 732 on-cDMARD intervals and 1027 off-cDMARD intervals were obtained from enrolled patients. In multivariable regression analysis, there was no significant association between cDMARDs and the rate of mSASSS progression (β = −0.081, p = 0.418). The mean adjusted mSASSS change per year was 0.610 from on-cDMARD intervals and 0.691 from off-cDMARD intervals.Conclusion:Treatment with cDMARDs may not reduce radiographic progression in AS patients.

Alcohol consumption as a predictor of the progression of spinal structural damage in axial spondyloarthritis: data from the Catholic Axial Spondyloarthritis COhort (CASCO)

BackgroundThe purpose of the present study was to demonstrate whether alcohol consumption could predict spinal structural damage in axial spondyloarthritis (axSpA) in a prospective cohort study.MethodsAxSpA patients were enrolled from a single tertiary hospital in a prospective cohort. Baseline data were collected, and 2-year follow-up radiographic data were collected. We analyzed the progression of spinal structural damage in 278 axSpA patients and grouped them into alcohol drinkers and non-drinkers. Baseline and follow-up characteristics were compared between the two groups. Univariable and multivariable logistic regression analyses were performed to reveal predictors of spinal structural damage.ResultsChanges in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and syndesmophyte count over the 2-year period were more prominent in the alcohol drinker group than in the non-drinker group (2.7 ± 3.6 vs 1.5 ± 2.8, P = 0.007, 0.9 ± 1.3 vs 0.4 ± 1.2, P = 0.003). The alcohol drinker group showed more frequent significant mSASSS changes (≥ 2 units for 2 years follow-up) and new syndesmophyte/progression of pre-existing syndesmophytes than the non-drinker group (60.7% vs 29.2%, P < 0.001, 51.5% vs 26.4%, P < 0.001, respectively). On univariable and multivariable regression analyses, drinking alcohol showed a significant relationship with the progression of spinal structural damage for both mSASSS and syndesmophyte progression.ConclusionThe present study showed the association between alcohol consumption and spinal structural progression in axSpA patients for the first time.

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.

Spinal radiographic progression over 2\xa0years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison

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

Effect of anti-tumor necrosis factor α treatment on radiographic progression in patient with ankylosing spondylitis: A systematic review and meta-analysis

Background: Efficacy of anti-tumor necrosis factor (anti-TNF)α treatment in patient with active ankylosing spondylitis (AS) had been proved by many clinical studies. Inflammation and new bone formation in spine were two pivotal aspects in AS. TNF α inhibitor could eliminate inflammation including clinical and laboratory inflammatory manifestation. Paradoxical results whether TNF α antagonist could delay radiographic progression in AS were often been reported simultaneously.Objectives: To review the literature about the effect of TNF α inhibitor on radiographic progression and disease activity in patient with AS.Methods: We conducted a comprehensive search including Medline, EMBASE and the Cochrane Library from 1 January 2000 to 15 August 2017. Two reviewers independently supplemented with hand searching for the reference lists of inclusion. All trials focusing on radiographic progression or disease activity in patients with AS treated with anti-TNF α agents. Primary outcomes were modified Stokes AS Spinal Score (mSASSS), as well as Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI). Two reviewers independently selected studies and analyzed data. Methodological quality was assessed using the Newcastle-Ottawa scale (NOS). We pooled effects recorded on different scales as Standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models.Results: We included 14 studies of low to moderate risk of bias with 3,186 patients, compared with control group, there was no effect of mSASSS changes (SMD = –0.12, 95% CI: –1.17–0.93, p value = .82, I2 = 95%) and follow-up (SMD = 0.03, 95% CI: 0.21–0.26, p value = .82, I2 = 36%) estimation in anti-TNF α group. However anti-TNF α agent treatment led to remarkable improvements on both Bath AS disease activity index (BASDAI) (SMD = 1.06, 95% CI: 0.22–1.89, p value = .01, I2 = 96%) and Bath AS functional index (BASFI) (SMD = 0.93, 95% CI: 0.24–1.92, p value = .01, I2 = 97%) scores at 12 weeks.Conclusion: Our meta-analysis found no significant effect on delaying radiographic progression in AS treated with TNF α inhibitor, although TNF α inhibitor could do improve significantly disease activity and physical function in AS.

Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study.

ObjectiveTo evaluate the effect of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, on efficacy, imaging outcomes, and safety through 4 years (208 weeks) in patients with ankylosing spondylitis.MethodsPatients opting to enrol had completed 2 years’ treatment in the MEASURE 1 core study with subcutaneous secukinumab 150 or 75 mg every 4 weeks (q4Wk), following intravenous loading to Week (Wk) 4, or placebo treatment to Wk16/24. Up-titration from secukinumab 75–150 mg q4Wk was permitted following a protocol amendment. Efficacy is reported for patients originally randomized to secukinumab. Radiographic changes were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and changes in MRI measures of inflammation using the Berlin scoring method. Safety and tolerability were evaluated.ResultsAmong 274 extension study participants, 89.7% (78/87) and 93.0% (93/100) originally randomized to secukinumab 150 and 75 mg, respectively, completed 208Wk. Through Wk208, Assessment of Spondyloarthritis International Society 20/40 (observed) were 79.7%/60.8% (150 mg), 71.0%/43.5% (75 mg) and 80.0%/76% (up-titrators; n = 25). Mean (s.d.) changes in mSASSS were 1.2 (3.91) (150 mg), 1.8 (4.32) (75 mg) and 1.6 (5.67) (up-titrators). No radiographic progression (mSASSS change from Baseline < 2) was observed in 79% of patients receiving either secukinumab dose. Exposure-adjusted incidence rates per 100 patient-years were: serious infections (1.0), Candida infections (0.4), Crohn’s disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5), with no new safety signals.ConclusionThrough 4 years, secukinumab provided sustained efficacy on signs and symptoms, and MRI outcomes, a low rate of radiographic progression and a consistent safety profile.Trial registrationNCT01863732.

Relationship between serum adipokine levels and radiographic progression in patients with ankylosing spondylitis: A preliminary 2-year longitudinal study.

The immunomodulatory effects of adipokines have been extensively studied in rheumatic diseases, and there is a paucity of information regarding their effects on bone metabolism.The aim of this study was to investigate the relationships between serum adipokines levels and radiographic progression over 2 years in patients with ankylosing spondylitis (AS).In this preliminary longitudinal study, we prospectively recruited 20 consecutive male patients with AS and 11 gender- and age-matched healthy subjects. At the baseline and 2-year follow-up, serum adiponectin, leptin, resistin, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Dickkopf-1(DKK-1) levels were measured in AS patients using enzyme-linked immunosorbent assays; these measurements were only performed at the baseline for healthy controls. Radiographic progression was determined as the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression of ≥2 by comparing the baseline and 2-year follow-up radiographs.All AS patients were naive to TNF-α blockers at the enrollment and during the 2-year follow-up period and their median disease duration was 51.5 months. At the baseline, the serum resistin, TNF-α, and IL-6 levels were significantly higher in AS patients than in controls. At the 2-year follow-up, the median mSASSS of AS patients was found to be significantly increased from the baseline (8–10.5, P = .001) and 7 (35%) AS patients showed radiographic progression. In AS patients, the leptin and resistin levels were significantly higher at the 2-year follow-up than at the baseline. The baseline resistin levels and changes in leptin levels from the baseline to the 2-year follow-up were significantly higher in AS patients with radiographic progression than in those without radiographic progression (P = .002 and .024, respectively). The baseline resistin levels and the increase in leptin levels during the follow-up period significantly correlated with changes in mSASSS (ρ = 0.528 and 0.559, P = .017 and .01, respectively). No association between changes in serum adipokine levels and disease activity in AS patients was observed.Our findings suggest that leptin and resistin may contribute to the pathogenesis of new bone formation rather than to inflammatory processes and have the potential to be used as biomarkers of the structural outcome of AS.

Baseline extent of damage predicts spinal radiographic progression in Korean patients with ankylosing spondylitis treated with golimumab

Background/AimsFor patients with ankylosing spondylitis (AS), golimumab has consistent efficacy in controlling disease activity over 5 years but its benefit in preventing radiographic progression was less clear at 4 years. To predict radiographic progression, we analyzed the baseline characteristics of AS patients in a Korean population.MethodsSixty-eight Korean patients with AS participated in the phase 3, multicenter, randomized, placebo-controlled, double-blind trial (GO-RAISE) which has previously been described. Baseline modified stoke AS spine score (mSASSS) and change in mSASSS from baseline (ΔmSASSS) until week 208 were analyzed in the Korean patients enrolled in the GO-RAISE study.ResultsAlthough Korean patients had lower baseline mSASSS compared to non-Korean patients and received active management, radiographic progression was not prevented. Korean patients who did not undergo radiographic progression of spinal lesions of AS were younger and had shorter symptomatic duration, lower Bath AS functional and metrology indices, better chest expansion, and lower baseline mSASSS. The baseline mSASSS and ΔmSASSS were positively correlated in Korean AS patients (p < 0.001). Radiographic progression was more prevalent (80.0%) when baseline mSASSS > 10 and less common (13.0%) with baseline mSASSS = 0.ConclusionsIn Korean AS patients, radiographic progression of the spine after 4 years was predicted effectively by the initial severity of the spinal lesion(s) in patients treated with golimumab.