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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 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][1]). These differences remained statistically significant after correcting for age, disease duration, and comorbidity. View this table: Table 1. Disease activity, physical function, and QoL of axial SpA patients with overweight and obesity compared to those 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 [1]: #T1

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are regarded as the cornerstone of conventional therapy in ankylosing spondylitis (AS). TNF-α blocking therapy is available for AS patients who have insufficient response to conventional therapy. However, little is known about concomitant NSAID use during TNF-α blocking therapy. Objectives The aim of the present study was to evaluate NSAID use in AS patients with and without TNF-α blocking therapy during 2-year follow-up. Methods The present analysis is part of the GLAS cohort, an ongoing longitudinal observational cohort study in daily clinical practice. Since November 2004, consecutive AS outpatients who started TNF-α blocking therapy because of active disease at the UMCG and the MCL were included. In 2009, this inclusion was extended to all consecutive AS outpatients, irrespective of treatment regimen. All patients fulfilled the modified New York criteria for AS (>90%) or the ASAS criteria for axial spondyloarthritis. At every follow-up visit, disease activity was assessed using Bath AS disease activity score (BASDAI), AS disease activity score (ASDAS), and C-reactive protein (CRP). NSAID use (yes/no) and type of NSAID were recorded prospectively. In addition, dosage and frequency were assessed retrospectively from clinical records and the recently developed ASAS-NSAID index was calculated. NSAID use during the first 2 years of follow-up was compared between patients with and without TNF-α blocking therapy. Results Of the 407 included patients, 66% were male, 73% HLA-B27 positive, mean age was 43.5 years (SD ±12.6), and median symptom duration 15 years (range 1-59). These patient characteristics were comparable between patients with (n=270) and without (n=137) TNF-α blocking therapy. As expected, patients who started TNF-α blocking therapy had significantly higher disease activity at baseline (median BASDAI 6.0 vs. 3.6, ASDAS 3.7 vs. 2.3, CRP 12 vs. 4; p Of the 270 patients who started TNF-α blocking therapy, 79% used NSAIDs at baseline and this proportion decreased significantly during follow-up; 40% after 12 months (p Conclusions In this observational cohort study in daily clinical practice, there was no difference in NSAID use between AS patients with and without indication for starting TNF-α blocking therapy. During TNF-α blocking therapy, the proportion of patients who used concomitant NSAIDs decreased significantly over time. NSAID use remained stable in patients without 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 M. Carbo: None declared, S. Arends Grant/research support: Abbott, Pfizer, Wyeth, E. Brouwer Grant/research support: Abbott, Pfizer, Wyeth, R. Bos Grant/research support: Pfizer, Consultant for: Pfizer, M. Efde: None declared, M. Leijsma: None declared, H. Bootsma: None declared, E. van der Veer: None declared, A. Spoorenberg Grant/research support: Abbott, Pfizer, Wyeth, Consultant for: Abbvie, Pfizer, UCB DOI 10.1136/annrheumdis-2014-eular.4947

Background There are differences in clinical presentation of ankylosing spondylitis (AS). Women tend to have milder disease and may therefore be underdiagnosed. Male AS patients are more likely to develop spinal radiographic damage. Objectives The aim of the present study was to investigate whether there are differences in patient-reported assessments of disease activity, physical function, and quality of life between male and female patients with axial spondyloarthritis (SpA). Methods All 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 AS (>90%) or the ASAS criteria for axial SpA. Disease activity was assessed using Bath AS disease activity index (BASDAI), AS disease activity score (ASDAS; calculated from BASDAI questions 2, 3 and 6, patient global assessment of disease activity (GDA), and C-reactive protein (CRP)), swollen joint index (range 0-44), and tender joint index (range 0-46). Physical function was assessed using Bath AS functional index (BASFI) and quality of life using AS quality of life (ASQoL) questionnaire. Results Of the 469 included patients, mean age was 45 years (SD ±13), mean duration of symptoms was 17 years (range 0-61), 66% were male, and 80% were HLA-B27+. Males were significantly older, had longer disease duration, and were more frequently HLA-B27+ compared to females. Extra-articular manifestations, comorbidity, and current use of NSAID, DMARD, and anti-TNF were comparable between both groups. Patient-reported measures of disease activity (BASDAI, patient GDA, and tender joints) and outcome (BASFI and ASQoL) were significantly higher in female compared to male patients. ASDAS, capturing both subjective and objective aspects of disease activity, was also significantly higher in females. This difference can be explained by patient-reported aspects of the ASDAS, since CRP levels were comparable between male and female patients (Table 1). Differences remained statistically significant after correcting for age, disease duration, and HLA-B27 status. Conclusions This cross-sectional study shows that patient-reported measures of disease activity and outcome as well as ASDAS were significantly worse in female axial SpA patients. We recommend to be aware of these differences when interpreting patient-reported measures in research and clinical practice. 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.4330

Background Physical activity questionnaires are considered to be the most applicable method to assess daily physical activity in population studies because of participant convenience, minimal cost, and scoring flexibility. The International Physical Activity Questionnaire (IPAQ) and the Short QUestionnaire to Asses Health-enhancing physical activity (SQUASH) are recall questionnaires that have acceptable construct validity and moderate to high test-retest reliability in healthy populations.(1,2) Until now, the validity and reliability of these physical activity questionnaires have not been studied in patients with ankylosing spondylitis (AS). Objectives To investigate the construct validity and test-retest reliability of the IPAQ and SQUASH in patients with AS. Methods The self-report questionnaires IPAQ (long form) and SQUASH were compared with daily physical activity assessed using the ActiGraph accelerometer during 7 consecutive days (gold standard) in 63 AS outpatients. The IPAQ and SQUASH were administered on two different occasions approximately one week apart in 52 AS outpatients. All patients fulfilled the modified New York criteria for AS or the ASAS criteria for axial spondyloarthritis. Validity was examined by calculating Spearman’s and Pearson’s correlation coefficients between accelerometer activity counts and IPAQ and SQUASH total scores, respectively. Test-retest reliability of the IPAQ and SQUASH was investigated by calculating intraclass correlation coefficients (ICC) between the first and the second assessments of the questionnaires. Additionally, Bland-Altman analysis was performed. Results Mean age of the in total 115 AS patients was 45 years (SD ± 12), median disease duration was 16 years (range 0-54), and 62% were male. IPAQ and SQUASH total scores correlated significantly with accelerometer outcome: ρ=0.38 and r=0.35, respectively. ICC’s between first and second assessments of the IPAQ and SQUASH were 0.83 and 0.89, respectively. Bland-Altman analyses showed no systemic bias, but in particular for the IPAQ the 95% limits of agreement were wide. Conclusions Both physical activity questionnaires showed moderate construct validity. The SQUASH showed good test-retest reliability, superior to the IPAQ. These results indicate that the SQUASH can be used to assess daily physical activity in AS population studies. References Craig CL, Marshall AL, Sjostrom M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35:1381-95. Wendel-Vos GC, Schuit AJ, Saris WH, et al. Reproducibility and relative validity of the short questionnaire to assess health-enhancing physical activity. J Clin Epidemiol. 2003;56:1163-9. Disclosure of Interest None Declared

Background Ankylosing spondylitis (AS) is characterized by the combination of inflammation, bone formation, and bone loss. New bone formation can lead to the formation of syndesmophytes, ankylosis of the spine and sacroiliac joints, and bone formations on enthesal sites, whereas bone loss can result in osteoporosis and vertebral fractures. Objectives To investigate the relation between bone turnover markers (BTM) and the presence of (bridging) syndesmophytes and/or low bone mineral density (BMD) in AS patients with active disease. Methods 149 consecutive outpatients with AS based on the modified New York criteria and active disease (Bath AS disease activity index (BASDAI) ≥4 and/or based on expert opinion) were included. Patients with recent fractures ore use of bisphosphonates were excluded. The lateral view of radiographs of the cervical and lumbar spine were scored for the presence of (bridging) syndesmophytes at the anterior corners of the vertebrae by two independent observers. In case of discrepancy between the observers, consensus was reached afterwards. BMD of the lumbar spine (anterior-posterior projection at L1-L4) and hip (total proximal femur) were measured using DXA. Low BMD was defined as a lumbar spine and/or hip BMD Z-score ≤1. Markers of bone formation procollagen type 1 N-terminal peptide (PINP) and bone-specific alkaline phosphatase (BALP), and marker of bone resorption serum collagen-telopeptide (sCTX) were measured. Z-scores of BTM were calculated using matched 10-years-cohorts of a Dutch reference group (200 men or 350 women) to correct for the normal influence that age and gender have on bone turnover. Results Mean age was 42 years (SD±11), median symptom duration 15 years (range: 1-53), mean BASDAI 6.2 (SD±1.6), and 70% were male. Syndesmophytes, bridging syndesmophytes, and low BMD were present in 68%, 33%, and 42% of the patients, respectively. No significant differences in BTM were found between patients with and without syndesmophytes. Patients with bridging syndesmophytes had significantly higher PINP Z-scores (median: 0.55 vs. -0.01, p=0.002) and sCTX Z-scores (median: 0.44 vs. -0.52, p=0.000) than patients without bridging syndesmophytes. Patients with low BMD had significantly higher sCTX Z-scores (median: -0.03 vs. -0.61, p=0.010) than patients with normal BMD. The differences in sCTX Z-score remained statistically significantly after correcting for gender, age, disease duration, and disease activity. Conclusions This cross-sectional analysis in AS patients with active and relatively long-standing disease indicates that higher serum levels of sCTX are significantly associated with the presence of bridging syndesmophytes and/or low BMD. Longitudinal studies are needed to investigate whether BTM can serve as potential biomarkers or predictors for radiographic progression and/or osteoporosis in AS. Disclosure of Interest None Declared

Background Inflammation in Rheumatoid Arthritis leads to impaired bone formation. The activity of the Wnt pathway influences osteoblast differentiation. Dickkopf-1 (Dkk1) and Sclerostin (Sost) are important negative regulators of bone formation, they bind and inactivate signaling of the LRP-5 receptor. This inhibition is amplified in case Dkk-1 also binds to the transmembrane receptor Kremen-1. Data are emerging that Wnt signaling is important to maintain the integrity of joints and that TNF-α induced changes in Dkk-1 affect the balance between bone formation and resorption. Objectives Since the severity of joint destruction in Rheumatoid Arthritis is in part influenced by genetic factors, we aimed to study the influence of genetic variants in Dkk-1 , Sost , LRP-5 and Kremen-1 on the radiographic progression rate. Methods 1,418 RA-patients with 4,885 X-ray sets of both hands and feet of four independent cohorts were studied. First, explorative analyses were performed on 600 RA-patients enrolled in the Leiden-Early-Arthritis-Clinic on the SNPs tagging Dkk-1 (8), Sost (9), Kremen-1 (16) and LRP5 (44). Significantly associating SNPs were genotyped in cohorts from Groningen (NL), Sheffield (UK) and Lund (Sweden). In each dataset the relative increase of the progression rate per year in the presence of a genotype was assessed. Subsequently, data were summarized in a meta-analysis. In groups of 80, on their genotype selected, RA-patients from Leiden, serum levels of functional Dkk-1 and Sclerostin (Biomedica, Austria) were measured with ELISA and studied in relation to genotypes. Results In the first cohort, 7 SNPs on Dkk-1 , 3 SNPs on Sost , 1 SNP on Kremen-1 and 10 LRP-5 SNPs were significant. The SNPs on Kremen-1 and LRP-5 were not replicated in the second phase. 3 Dkk-1 SNPs associated significantly with progression of joint damage in the meta-analysis, also after FDR-correction for multiple testing (rs1896368, rs1896367 and rs1528873). Additionally, 2 Sost SNPs tended to significance (rs4792909 and rs6503475, p=0.01 and 0.03 in the meta-analysis and p=0.07 after FDR-correction). Epistasis between SNPs on Dkk-1 and Sost was observed. Sclerostin levels were not correlated to the SNPs in Sost . However, serum levels of Dkk-1 were significantly correlated with the genotypes in rs1896368 and rs1896367 (p=0.002). Patients carrying risk alleles (associated with more radiographic progression) had higher levels of Dkk-1. Conclusions The present data of four cohort studies show that RA-patients carrying the risk alleles of several genetic variants in Dkk-1 have higher serum levels of functional Dkk-1 and more progressive joint destruction over time. These data illustrate the relevance of Dkk-1 to progression of joint destruction in RA. Disclosure of Interest None Declared

Background In ankylosing spondylitis (AS), objective measurements evaluating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy are lacking. Objectives To investigate the predictive value of bone turnover markers (BTM) in relation to discontinuation of TNF-α blocking therapy in patients with AS. Methods 111 consecutive AS outpatients from the Medical Center Leeuwarden and the University Medical Center Groningen who started TNF-α blocking therapy (infliximab n=22; etanercept n=71; adalimumab n=18) were included between November 2004 and December 2007. All patients fulfilled the modified New York criteria for AS (n=109) or the ASAS criteria for axial spondyloarthritis (n=2). Patients with recent fractures and/or use of bisphosphonates were excluded. Continuation of TNF-α blocking therapy was based on decrease in Bath AS Disease Activity Index (BASDAI) of at least 50% or 2 units compared with baseline, and/or expert opinion in favor of treatment continuation. Clinical assessments, marker of bone formation bone-specific alkaline phosphatase (BALP), and marker of bone resorption serum collagen-telopeptide (sCTX) were assessed at baseline, 3 and 6 months, and 1, 2, and 3 years. Z-scores of BTM were calculated using matched 10-years-cohorts of a Dutch reference group (200 men or 350 women) to correct for the normal influence that age and gender have on bone turnover. Results Mean age of the 111 AS patients was 42.2 years (SD ± 10.3), median disease duration was 16 years (range 1-49), and 70% were male. Mean BASDAI was 6.1 (SD ± 1.7) and mean AS disease activity index (ASDAS) was 3.8 (SD ± 0.8) at baseline. After 3 years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased BALP Z-score and significantly decreased sCTX Z-score compared to baseline. Baseline to 3 months decrease in sCTX Z-score (HR: 0.513, 95% CI: 0.367-0.717) was inversely associated with time to discontinuation of TNF-α blocking therapy in univariate Cox regression. Multivariate analysis showed that baseline to 3 months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263-0.591), ASDAS (HR: 0.488, 95% CI: 0.317-0.752), and physician’s global disease activity (GDA) (HR: 0.739, 95% CI: 0.600-0.909) were independent inversely related predictors of time to treatment discontinuation. Conclusions In addition to the ASDAS and physician’s GDA, early change in bone resorption marker sCTX after starting treatment can serve as an objective measure in the prediction of long-term continuation of TNF-α blocking therapy in AS. Disclosure of Interest None Declared