E. van der Veer

The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease: a cross-sectional analysis

SummaryOsteoporosis is a well recognized complication of ankylosing spondylitis (AS). This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis, and that bone turnover markers (BTM) are valuable markers to detect bone loss in AS.IntroductionThe aim of this study was to elucidate the pathophysiology of AS-related osteoporosis by investigating the relation between bone mineral density (BMD), BTM, vitamin D, and clinical assessments of disease activity and physical function, as well as to identify parameters that are related to low BMD (osteopenia or osteoporosis) in AS patients with active disease.MethodsOne hundred twenty-eight consecutive Dutch AS outpatients were included in this cross-sectional study. Bath AS Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), C-reactive protein, ASAS-endorsed disease activity score (ASDAS), Bath AS Functional Index (BASFI), bone formation markers procollagen type 1 N-terminal peptide (PINP) and osteocalcin (OC), bone resorption marker serum C-telopeptides of type I collagen (sCTX), 25-hydroxyvitamin D (25OHvitD), lumbar spine and hip BMD, and vertebral fractures were assessed. Z-scores of BTM were calculated using matched 10-year cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover.ResultssCTX Z-score, OC Z-score, BASDAI, age, and gender were independently related to low BMD. In addition, PINP Z-score, ESR, 25OHvitD, age, and gender were independently related to sCTX and/or OC Z-score.ConclusionsThis study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis. Furthermore, sCTX and OC Z-scores seem to be valuable markers to detect bone loss in AS patients in daily clinical practice where BMD of the lumbar spine, measured by DXA, may be overestimated due to osteoproliferation in patients with advanced AS.

Inflammation, vascular injury and repair in rheumatoid arthritis

The systemic pro-inflammatory state present in patients with rheumatoid arthritis (RA) accelerates the progression of atherosclerosis through chronic endothelial activation. Uncoupling of endothelial nitric oxide synthase plays a central role in the amplification of oxidative signalling pathways that chronically activate and, ultimately, injure the endothelium. Recent studies indicate that the resultant loss of endothelial integrity in patients with RA may also involve defects in the vascular regenerative potential provided by circulating endothelial progenitor cells (EPC). This is most likely the consequence of endothelial cell dysfunction in the bone marrow stroma, which hampers the mobilisation of these EPC to the circulation. In addition, mediators of systemic inflammation in RA can affect a second pathway of vascular regeneration. Under normal circumstances, myeloid CD14+ cells can adopt a pro-angiogenic phenotype that plays a key role in vascular remodelling and collateral formation. However, the chronic systemic inflammation observed in patients with RA may skew the differentiation of bone marrow and circulating CD14+ cells in such a way that these cells lose their capacity to support collateral formation, increasing the risk of cardiovascular disease. Taken together, in patients with RA, the impaired capacity of circulating cells to support vascular regeneration may comprise a novel pathway in the development of premature atherosclerosis.

Serum MMP-3 Level as a Biomarker for Monitoring and Predicting Response to Etanercept Treatment in Ankylosing Spondylitis

Objective. To investigate whether level of serum matrix metalloproteinase-3 (MMP-3) can serve as a biomarker for monitoring and predicting response to etanercept treatment in patients with ankylosing spondylitis (AS) in daily clinical practice. Methods. Ninety-two consecutive AS outpatients with active disease who started etanercept treatment were included in this longitudinal observational study. Clinical data were collected prospectively at baseline and after 3 and 12 months of treatment. At the same timepoints, serum MMP-3 levels were measured retrospectively by ELISA. Results. Since baseline serum MMP-3 levels were significantly higher in male compared to female patients with AS, data analysis was split for gender. Changes in serum MMP-3 levels after etanercept treatment correlated positively with changes in clinical assessments of disease activity and physical function in both male and female patients. Receiver operating characteristic analysis in male patients showed that baseline serum MMP-3 levels had poor accuracy (AUC < 0.7) to discriminate between Assessments in Ankylosing Spondylitis 20 (ASAS20) or ASAS40 responders and nonresponders after 3 or 12 months of treatment. The accuracy of change in serum MMP-3 levels from baseline to 3 months in predicting response after 3 or 12 months of treatment was poor for ASAS40 (AUC < 0.7) or moderate for ASAS20 (AUC = 0.752 and 0.744, respectively), and was not superior to the accuracy of change in the currently used objective biomarkers, erythrocyte sedimentation rate and C-reactive protein. Conclusion. Although significant changes in serum MMP-3 levels were found after etanercept treatment, data analysis indicates that serum MMP-3 levels are not very useful for monitoring and predicting response to etanercept treatment in patients with AS in daily clinical practice.

MicroRNA-155 Functions as a Negative Regulator of RhoA Signaling in TGF-β-induced Endothelial to Mesenchymal Transition

Endothelial to mesenchymal transition (EndoMT) has been proposed to be involved in the loss of microvascular capillaries in the pathophysiology of fibrosis and organ failure. In EndoMT, endothelial cells (EC) undergo a mesenchymal transition associated with the loss of cell-cell contacts and the acquisition of a synthetic, contractile phenotype. Here, we sought to identify microRNAs (miRNAs) that could play a central role in regulating EndoMT. In a TGF-β dependent in vitro model for EndoMT, we identified miRNAs that were differentially expressed in normoxic and hypoxic conditions. These studies identified miR-155 to be significantly upregulated in EndoMT, an effect that was enhanced under hypoxia, which further augments EndoMT. Silencing of miR-155 directly increased RhoA expression and activity in endothelial cells and affected phosphorylation of downstream LIMK. In contrast, overexpression of miR-155 counteracted RhoA function. Using a selective Rho kinase inhibitor, we could partly suppress EndoMT, strengthening the notion that RhoA plays a central role in EndoMT. Forced overexpression of miR-155 completely suppressed EndoMT, as evidenced by the maintenance of EC characteristics and blocking the acquisition of a mesenchymal phenotype, as compared to control cells. Our data demonstrate that miRNA-155 functions as a negative regulator of RhoA signaling in TGF-β-induced endothelial to mesenchymal transition.

THU0077 Prevalence of Obesity and the Relation to Disease Activity, Physical Function, and Quality of Life in Patients with Axial Spondyloarthritis

Background Obesity is associated with an increased risk for many disorders, impaired functional capacity, and impaired quality of life (QoL). Objectives The aim of the present study was to evaluate the prevalence of obesity and the relation to clinical assessments of disease activity, physical function, and QoL in patients with axial spondyloarthritis (SpA). Methods 465 consecutive patients from the Groningen Leeuwarden Axial SpA (GLAS) cohort who visited the outpatient clinic between January 2011 and December 2012 were included in this cross-sectional analysis. All patients fulfilled the modified New York criteria for ankylosing spondylitis (AS; >90%) or the ASAS criteria for axial SpA. Body mass index (BMI) was calculated and patients were divided into groups according to the WHO criteria: low BMI (BMI <18.5 kg/m2), normal BMI (BMI 18.5-25 kg/m2), overweight (BMI 25-30 kg/m2), and obesity (BMI >30 kg/m2). BMI was compared with the LifeLines cohort, a three generation population-based longitudinal cohort study in the North of the Netherlands. Disease activity was assessed by Bath AS Disease Activity Index (BASDAI), AS Disease Activity Score (ASDAS), and C-reactive protein (CRP), physical function by Bath AS Functional Index (BASFI), and quality of life by ASQoL questionnaire. Results Mean age of the 465 patients was 45 years (SD ±13), median symptom duration was 17 years (range 0-61), 65% were male, and median BMI was 26.0 kg/m2 (range 17.0-45.4). In total, 8 (2%) patients had low BMI, 183 (39%) had normal BMI, 174 (37%) were overweight, and 100 (22%) were obese. Of the 100 obese patients, 19 had BMI between 35-40 kg/m2 and 3 had BMI >40 kg/m2. In comparison, the LifeLines population (n=136577) had an estimated prevalence of 1% low BMI, 42% normal BMI, 43% overweight, and 15% obesity. Obese axial SpA patients were significantly older, had longer disease duration, and more comorbidity than patients with normal BMI. Disease activity of obese patients was significantly higher and physical function and QoL were significantly worse compared to patients with normal BMI (Table 1). These differences remained statistically significant after correcting for age, disease duration, and comorbidity. Table 1. Disease activity, physical function, and QoL of axial SpA patients with overweight and obesity compared to those with normal BMI Normal Overweight P-value* Obesity P-value* BMI [18.5–25] BMI [25–30] BMI [>30] (n=183) (n=174) (n=100) BASDAI (range 0–10) 3.4 (0–9.2) 3.5 (0–9.6) 0.235 4.4 (0.6–9.4) 0.029 ASDAS(CRP) 2.1 (0–5.2) 2.1 (0.3–5.1) 0.983 2.7 (0.5–5.7) 0.000 CRP (mg/L) 3.0 (0–73) 3.0 (0–94) 0.372 5.0 (0–82) 0.000 CRP ≥5 mg/L 62 (34) 56 (32) 0.795 53 (53) 0.001 BASFI (range 0–10) 2.9 (0–9.1) 2.7 (0–9.9) 0.635 5.1 (0.1–9.7) 0.000 ASQoL (range 0–18) 5.0 (0–17) 4.0 (0–18) 0.077 8.0 (0–18) 0.002 Values are presented as median (range) or number of patients (%). *P-values compared to patients with normal BMI. Conclusions This cross-sectional analysis shows a high prevalence of obesity in a large cohort of axial SpA patients. The presence of obesity was associated with higher disease activity and worse physical function and QoL. Acknowledgements The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4363

SAT0416 Ankylosing spondylitis disease activity score (ASDAS) is associated with nsaid use over time

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of conventional treatment in ankylosing spondylitis (AS). In case of insufficient response, tumor necrosis factor-alpha (TNF-α) inhibitors are available. Still little is known about concomitant NSAID use. Objectives To investigate the longitudinal association between disease activity and NSAID use in established AS patients. Methods The present analysis is part of the GLAS cohort, an ongoing longitudinal observational axial spondyloarthritis (SpA) cohort study in daily clinical practice. During 52 weeks of follow-up, NSAID use was recorded prospectively. The ASAS-NSAID index was calculated using the dosage and frequency assessed retrospectively from clinical records. Disease activity was assessed using ASDAS, BASDAI, and serum CRP levels. Generalized estimating equations (GEE) was used to evaluate NSAID use in relation to assessments of disease activity over time. NSAID use was analyzed using 4 parameters: NSAID use (yes/no), ASAS-NSAID index, low on demand use (index ≥10 versus <10), and high use (index ≥90 versus <90). Analyses were stratified for treatment regimen: patients starting TNF-α inhibitors and patients on conventional treatment. Results Of the 393 included AS patients, 67% were male, mean age was 44±13 years, median symptom duration 15 years (IQR 8–24), and 79% were HLA-B27 positive. In total, 254 (66%) patients started TNF-α inhibitors and 139 (34%) patients received conventional treatment. Patient characteristics were comparable between both groups, except higher disease activity, more often peripheral arthritis, and worse physical functioning in patients starting TNF-α inhibitors. NSAID use and disease activity reduced significantly after starting TNF-α inhibitors and remained low and stable during follow-up. In the conventional treatment group, disease activity was low and NSAID remained stable at all visits. GEE analysis over time showed that NSAID use was significantly associated with disease activity (Table 1). In the TNF-α inhibitor group, a significant association of all NSAID parameters with ASDAS was found: NSAID use yes vs. no, ASAS-NSAID index, index ≥10 vs. <10, and index ≥90 vs. <90. Comparable results were found for BASDAI and CRP. The association between NSAID use and ASDAS remained significant in the 217 patients who used TNF-α inhibitors more than 80% of the follow-up time and when analyzing only 12 to 52 weeks of follow-up to exclude the initial effect of TNF-α inhibitors, although the regression coefficients were lower in these last analyses. In the conventional treatment group, a significant but less prominent association of NSAID parameters with ASDAS was found: NSAID use yes vs. no, index ≥10 vs. <10, and index ≥90 vs. <90. BASDAI was only significantly associated with on demand NSAID use. For CRP, no significant associations with NSAID use were found. Conclusions In this observational cohort of established AS patients, NSAID use over time was significantly associated with ASDAS, which was most pronounced for patients treated with TNF-α inhibitors. Acknowledgements The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. Disclosure of Interest None declared

FRI0413 Clinical Risk Factors for The Presence and Development of Vertebral Fractures in Patients with Ankylosing Spondylitis

Background Vertebral fractures are the hallmark of bone fragility and are frequently present in patients with ankylosing spondylitis (AS). For treating rheumatologists, it is important to know which patients already have vertebral fractures and which patients are at risk to develop new fractures. Limited longitudinal data are available concerning the development of new vertebral fractures in AS. Objectives To investigate the prevalence and incidence of radiographic vertebral fractures and the association with patient characteristics, clinical assessments, and medication use in a large prospective cohort of patients with ankylosing spondylitis (AS) in daily clinical practice. Methods Consecutive AS patients from the Groningen Leeuwarden AS (GLAS) cohort with baseline and 2-year lateral radiographs of the thoracic and lumbar spine were included. Radiographs were scored for vertebral fractures by two readers according to the method of Genant et al. Vertebral fractures were defined as ≥20% reduction in vertebral height. Severity of fractures were divided into mild (20–25% reduction), moderate (25–40% reduction), and severe (>40% reduction) fractures. Differences in baseline characteristics were explored between patients with and without radiographic vertebral fractures. Results Of 292 included AS patients, 70% were male, 82% HLA-B27+, mean age was 43±13 years, median symptom duration 16 (IQR: 8–25) years, and mean BASDAI 5.3±2.2. Radiographic vertebral fractures were present in 59 (20%) patients at baseline. During 2 years of follow-up, 15 (6%) patients developed new vertebral fractures and 7 (2%) showed an increase in severity of existing fractures. Most fractures were mild and located in the mid-thoracic and thoracolumbar region of the spine. The presence of vertebral fractures was significantly associated with older age, higher BMI, longer smoking duration, larger occiput-to-wall distance, more spinal radiographic damage, and lower hip BMD. Occiput-to-wall distance was identified as an independent risk factor for prevalent vertebral fractures; 44% of the patients with hyperkyphosis (occiput-to-wall distance ≥10 cm) had vertebral fractures. The development of new or progressive vertebral fractures was also associated with older age and low BMD. Patients using NSAIDs at baseline showed less prevalent (18% vs. 31%) and incident (5% vs. 17%) vertebral fractures than patients without NSAIDs. Conclusions In this large AS cohort in daily clinical practice, radiographic vertebral fractures were frequently present, especially in older patients with more advanced disease, low hip BMD, and a less healthy lifestyle. Interestingly, NSAID use was associated with a reduced vertebral fracture risk. Acknowledgement The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. Disclosure of Interest F. Maas: None declared, A. Spoorenberg Grant/research support from: Abbvie, Pfizer, UCB, Consultant for: Abbvie, Pfizer, MSD, UCB, Novartis, B. van der Slik: None declared, E. van der Veer: None declared, E. Brouwer Grant/research support from: Pfizer, H. Bootsma: None declared, R. Bos Grant/research support from: Pfizer, F. Wink Consultant for: Abbvie, S. Arends Grant/research support from: Pfizer

AB0658 Influence of Known Risk Factors on Spinal Radiographic Progression in Ankylosing Spondylitis Patients Receiving Long-Term Treatment with TNF Inhibitors: Results from The Glas Cohort

Background In ankylosing spondylitis (AS), the most important prognostic factor for spinal radiographic progression is the presence of syndesmophytes at study entry. In addition, male gender, older age, longer symptom duration, smoking, HLA-B27 positivity, and increased inflammatory markers were found to be associated with radiographic progression in AS.1 Objectives To investigate the influence of known risk factors on spinal radiographic progression in AS patients receiving long-term treatment with TNF inhibitors. Methods Consecutive patients from the GLAS cohort receiving TNF inhibitors with baseline and biannual spinal radiographs untill 6 years of follow-up were included. Radiographs were scored in chronological time order by two independent readers according to the mSASSS. Single linear imputation of radiographic data was used in case patients had missing data at one or more intermediate follow-up visits. The influence of the earlier mentioned risk factors for radiographic progression was investigated using univariable and multivariable generalized estimating equations (GEE). Subsequently, radiographic progression was modeled with different time functions (linear and non-linear) to provide the best fit for the data in patients with and without risk factors. A time function with p≤0.05 contributed significantly to the model and the estimated mean progression rates of the 2-year time intervals were calculated. Results Eighty patients were included; 70% were male, 78% HLA-B27+, mean age was 41±10 years, median symptom duration 14 (IQR: 8–24) years, mean BASDAI 6.0±1.7, mean ASDAS 3.8±0.8, and mean mSASSS 8.7±13.3. During 6 years of follow-up, mean progression was 4.2±4.8 mSASSS units. GEE revealed that baseline syndesmophytes, gender, age, and symptom duration were significantly associated with radiographic damage over time. No significant associations were found for smoking, HLA-B27 status, and elevated CRP levels. The presence of baseline syndesmophytes was the only independent predictor for progression. Baseline mSASSS was highest in AS patients with baseline syndesmophytes, male gender, age ≥40 years, and symptom duration ≥10 years. In these patients, mSASSS progression followed a non-linear course showing a reduction in estimated progression rates over time (Table 1). Most patients with syndesmophytes also had one or more other risk factors (e.g. male gender and symptom duration ≥10 years). A linear course with low estimated progression rates was found in patients without these risk factors (Table 1). Conclusions In our cohort of AS patients receiving long-term treatment with TNF inhibitors in daily clinical practice, patients with known risk factors for radiographic progression (especially the presence of baseline syndesmophytes) showed the highest radiographic damage scores at baseline and the highest but reducing radiographic progression over time. In contrast, patients without these risk factors showed less baseline damage and low linear progression rates. References Arends S, et al. Curr Opin Rheumatol. 2014;26:259–68. Acknowledgement The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. Disclosure of Interest F. Maas: None declared, S. Arends Grant/research support from: Pfizer, F. Wink Consultant for: Abbvie, E. van der Veer: None declared, R. Bos Grant/research support from: Pfizer, H. Bootsma: None declared, E. Brouwer Grant/research support from: Pfizer, A. Spoorenberg Grant/research support from: Abbvie, Pfizer, UCB, Consultant for: Abbvie, Pfizer, MSD, UCB, Novartis

The effect of bisphosphonates on bone mineral density in patients with ankylosing spondylitis in daily clinical practice

Background Ankylosing spondylitis (AS) is not only characterized by excessive bone formation, but also by excessive bone loss which may lead to low bone mineral density (BMD). So far, little is known about the effect of treatment with bisphosphonates on BMD in patients with AS. Objectives To evaluate the effect of bisphosphonates in combination with calcium/vitamin D supplements on BMD over 2 years in patients with AS stratified for the use of TNF-α inhibitors. Methods Patients from the Groningen Leeuwarden AS (GLAS) cohort, fulfilling the modified New York criteria for AS, who were treated with bisphosphonates and had 2-year follow-up BMD measurements available were included. All patients were treated with bisphosphonates in combination with calcium and/or vitamin D supplements. Alendronate (70 mg/week) and risedronate (35 mg/week) were used most frequently. BMD of the lumbar spine (anterior-posterior projection at L1-L4) and hip (total proximal femur) were measured using DXA. Wilcoxon-signed rank test was used to compare BMD scores at first visit and after 2 years. Analyses were stratified for the use of TNF-α inhibitors. Results In total, 28 patients were included; 68% were male, 82% HLA-B27+, mean age was 53 ± 14 years, median symptom duration 20 years (range 1–60), and mean BASDAI 5.1±2.5. Fifteen patients (54%) started treatment with bisphosphonates before inclusion in the GLAS cohort (median 3.1 years). Most patients (86%) used bisphosphonates during the entire 2-year follow-up within GLAS. Overall, lumbar spine BMD increased significantly from median Z-score of -0.8 at first visit to -0.3 after 2 years of treatment with bisphosphonates within the GLAS cohort. Hip BMD increased significantly from -1.1 at first visit to -0.9 after 2 years. In the 10 patients not using TNF-α inhibitors, only lumbar spine BMD increased significantly after 2 years of treatment. In the 14 patients starting TNF-α inhibitors, lumbar spine and hip BMD increased significantly after 2 years. The remaining 4 patients already used TNF-α inhibitors (Table 1). Comparable results were found for BMD T-scores. Conclusions In our observational cohort study, lumbar spine BMD improved significantly after 2 years of follow-up in all AS patients treated with bisphosphonates. This improvement was most pronounced in patients starting TNF-α inhibitors. Hip BMD only improved significantly in patients also starting TNF-α inhibitors. Acknowledgement The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. Disclosure of Interest S. Arends Grant/research support from: Pfizer, J. Veneberg: None declared, F. Wink Consultant for: Abbvie, R. Bos Grant/research support from: Pfizer, E. Brouwer Grant/research support from: Pfizer, E. van der Veer: None declared, H. Bootsma: None declared, E. van Roon: None declared, F. Maas: None declared, A. Spoorenberg Grant/research support from: Abbvie, Pfizer, UCB, Consultant for: Abbvie, Pfizer, MSD, UCB, Novartis

SAT0246 The Prevalence and Incidence of Radiographic Zygapophyseal Joint Involvement in Patients with Ankylosing Spondylitis Before and During 4 Years of TNF-Alpha Blocking Therapy

Background The zygapophyseal (ZA) joints of the cervical spine are frequently affected in ankylosing spondylitis (AS). Longitudinal data about the development of damage in the ZA joints is limited. Objectives To investigate the prevalence of radiographic ZA joint involvement in the cervical spine and to explore the associations with patient characteristics, clinical assessments, and cervical radiographic damage according to the modified Stoke AS Spine Score (mSASSS) in AS patients with active disease. Furthermore, to investigate the incidence of ZA joint involvement during 4 years of TNF-α blocking therapy. Methods This study included consecutive AS patients with active disease from the Groningen Leeuwarden AS (GLAS) cohort with available lateral cervical radiographs at baseline and after 4 years of follow-up. Patients fulfilled the modified New York criteria for AS and the ASAS criteria to start TNF-α blocking therapy. ZA joints of C2-C3 up to C6-C7 were scored by two trained and independent readers blinded to patient characteristics and time sequence according to the method of de Vlam et al. (0=normal, 1=joint space narrowing or erosion, 2=partial blurring or ankylosis, 3=complete blurring or ankylosis). ZA joint involvement was present if at least one ZA joint had a score ≥1. The mSASSS was scored to assess radiographic damage of the vertebral bodies and the presence of bridging syndesmophytes. Independent samples T-test, Mann-Whitney U test, and Chi-square test were used to evaluate the relationship with patient characteristics, clinical assessments, mSASSS, and bridging syndesmophytes. Results 108 patients were included with a mean age of 43±11 years, median symptom duration of 17 (range 1-50) years, 76% was male, 84% was HLA-B27 positive, mean BASDAI was 5.9±1.7, and mean ASDAS was 3.8±0.8. At baseline, 45% of the patients had ZA joint involvement with on average 3 ZA joints involved. Complete ankylosis of at least one ZA joint or of the entire cervical spine was present in 19% and 2% of the patients, respectively. Ankylosis occurred most frequently at C2-C3 level. Patients with ZA joint involvement were significantly older (46 vs. 40 year), had longer symptom duration (22 vs. 15 years), larger occiput-to-wall distance (9 vs. 2 cm), higher mSASSS (median 16 vs. 4), and more often bridging syndesmophytes (57% vs. 22%). After 4 years of follow-up, 8% of the patients had developed new ZA joint involvement. Furthermore, 18% of the patients who already had ZA joint involvement developed damage in other ZA joints. Conclusions In this cohort of AS patients with active disease, radiographic ZA joint involvement was very common and associated with assessments of more longstanding disease. The incidence of ZA joint involvement was low during 4 years of TNF-α blocking therapy. Acknowledgements The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. Disclosure of Interest F. Maas: None declared, S. Arends Grant/research support from: Abbott, Pfizer, Wyeth, E. van der Veer: None declared, F. Wink: None declared, M. Efde: None declared, H. Bootsma: None declared, R. Chaudhry: None declared, E. Brouwer Grant/research support from: Abbott, Pfizer, Wyeth, A. Spoorenberg Grant/research support from: Abbott, Pfizer, Wyeth, Consultant for: Abbvie, Pfizer, UCB