M. Efde

Obesity Is Common in Axial Spondyloarthritis and Is Associated with Poor Clinical Outcome

Objective. To assess the prevalence of overweight and obesity in a large cohort of patients with axial spondyloarthritis (axSpA) in comparison with the general population. To explore the relationship of body mass index (BMI) with clinical outcome in axSpA. Methods. Patients from the Groningen Leeuwarden Axial SpA cohort who visited the outpatient clinic in 2011/2012 were included in this cross-sectional analysis. Body weight, height, disease activity, physical function, and quality of life (QoL) were assessed. Patients were divided into normal weight (BMI < 25 kg/m2), overweight (BMI ≥ 25 to < 30 kg/m2), and obese (BMI ≥ 30 kg/m2). BMI data for the general population in the same demographic region, matched for age and sex, were obtained from the LifeLines Cohort Study. Results. Of the 461 patients with axSpA, 37% were overweight and 22% were obese. In the LifeLines cohort (n = 136,577), 43% were overweight and 15% were obese. Overweight and obese patients were older, had longer symptom duration, and had more comorbidities, especially hypertension. Further, obese patients had significantly higher disease activity, worse physical function, and worse QoL than overweight and normal weight patients (mean Bath Ankylosing Spondylitis Disease Activity Index 4.5, 3.5, 3.8; mean Ankylosing Spondylitis Disease Activity Score 2.8, 2.2, 2.3; median C-reactive protein 5, 3, 3 mg/l; median erythrocyte sedimentation rate 13, 8, 8 mm/h; median Bath Ankylosing Spondylitis Functional Index 5.2, 2.9, 2.9; median Ankylosing Spondylitis QoL Questionnaire 8, 4, 5, respectively). After adjustment for potential confounders, obesity proved to be an independent predictor of worse clinical outcome. Conclusion. In this large observational cohort study, obesity is more common in axSpA than in the general population and it is associated with worse clinical outcome.

Spinal Radiographic Progression in Patients with Ankylosing Spondylitis Treated with TNF-α Blocking Therapy: A Prospective Longitudinal Observational Cohort Study

Objectives To 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. Methods Consecutive 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. Results 176 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. Conclusions This 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.

Reduction in Spinal Radiographic Progression in Ankylosing Spondylitis Patients Receiving Prolonged Treatment With Tumor Necrosis Factor Inhibitors

To evaluate the course of spinal radiographic progression for up to 8 years of followup in a large cohort of ankylosing spondylitis (AS) patients treated with tumor necrosis factor (TNF) inhibitors.

Reduction in spinal radiographic progression in ankylosing spondylitis patients receiving prolonged treatment with TNF-α inhibitors.

To evaluate the course of spinal radiographic progression for up to 8 years of followup in a large cohort of ankylosing spondylitis (AS) patients treated with tumor necrosis factor (TNF) inhibitors.

Higher Bone Turnover Is Related to Spinal Radiographic Damage and Low Bone Mineral Density in Ankylosing Spondylitis Patients with Active Disease: A Cross- Sectional Analysis

Introduction Ankylosing spondylitis (AS) is characterized by excessive bone formation and bone loss. Our aim was to investigate the association of bone turnover markers (BTM) with spinal radiographic damage and bone mineral density (BMD) in AS patients with active disease. Methods 201 consecutive AS outpatients of the Groningen Leeuwarden AS (GLAS) cohort were included. Serum markers of bone resorption (C-telopeptides of type-I collagen, sCTX) and bone formation (procollagen type-I N-terminal peptide, PINP; bone-specific alkaline phosphatase, BALP) were measured. Z-scores were used to correct for the normal influence that age and gender have on bone turnover. Radiographs were scored by two independent readers according to modified Stoke AS Spinal Score (mSASSS). The presence of complete bridging (ankylosis of at least two vertebrae) was considered as measure of more advanced radiographic damage. Low BMD was defined as lumbar spine and/or hip BMD Z-score ≤ −1. Results Of the 151 patients with complete data, 52 (34%) had ≥1 complete bridge, 49 (33%) had ≥1 syndesmophyte (non-bridging), and 50 (33%) had no syndesmophytes. 66 (44%) had low BMD. Patients with bridging had significantly higher sCTX and PINP Z-scores than patients without bridging (0.43 vs. −0.55 and 0.55 vs. 0.04, respectively). Patients with low BMD had significantly higher sCTX Z-score than patients with normal BMD (−0.08 vs. −0.61). After correcting for gender, symptom duration, and CRP, sCTX Z-score remained significantly related to the presence of low BMD alone (OR: 1.60), bridging alone (OR: 1.82), and bridging in combination with low BMD (OR: 2.26). Conclusions This cross-sectional study in AS patients with active and relatively long-standing disease demonstrated that higher serum levels of sCTX, and to a lesser extent PINP, are associated with the presence of complete bridging. sCTX was also associated with low BMD. Longitudinal studies are needed to confirm that serum levels of sCTX can serve as objective marker for bone-related outcome in AS.

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

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

OP0040 Comparison of Radiographic Damage of the Zygapophyseal Joints and the Vertebral Bodies of the Cervical Spine in Patients With Ankylosing Spondylitis Before and After 4 Years Of Tnf-Alpha Blocking Therapy

Background Radiographic damage in the cervical spine is associated with restricted spinal mobility in patients with ankylosing spondylitits (AS). The most characteristic radiographic changes are syndesmophyte formation and ankylosis of the vertebral bodies. However, the zygapophyseal (ZA) joints are also involved in the disease process. Objectives To assess reliability of standardized scoring of the cervical ZA joints in AS patients. To compare radiographic damage of the ZA joints with radiographic damage of the vertebral bodies in AS patients with active disease before and after 4 years of TNF-α blocking therapy. Methods Consecutive AS patients with active disease from the GLAS cohort with available lateral radiographs of the cervical spine at baseline and after 4 years of TNF-α blocking therapy were included. ZA joints of C2-C3 up to C6-C7 were scored 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). The mSASSS was scored to assess radiographic damage of the vertebral bodies. Two readers were trained and after attaining good reliability radiographs were scored independently blinded to patient characteristics and time sequence. To compare damage of ZA joints and vertebral bodies, ZA joint involvement was defined as ≥1 ZA joint with score ≥1 and vertebral body involvement was defined as ≥1 vertebra with mSASSS ≥1. Linear weighted kappa statistics and percentage absolute agreement were used to analyze the reliability of the ZA joint scoring method. Results Of the 108 included patients, 76% was male, mean age was 43±11 years, median symptom duration 17 (1-50) years, 84% was HLA-B27 positive, mean BASDAI 5.9±1.7, and mean ASDAS 3.8±0.8. The ZA joint scoring method showed good interobserver reliability with kappas between 0.80-0.84 and high percentages of agreement between 80%>89%. At baseline, 49 (45%) patients had ZA joint involvement of which 22 (20%) had ankylosis in ≥1 ZA joint. In comparison with the vertebral bodies, 95 (88%) patients had mSASSS ≥1 of which 41 (38%) had mSASSS ≥3 (bridging syndesmophytes). In 4 (4%) patients, ZA joint involvement was present without vertebral body involvement. During 4 years of follow-up, 18 (14%) patients developed new damage in the ZA joints of which 3 (3%) developed ankylosis in ≥1 ZA joint. Development of new damage of vertebral bodies was present in 66 (61%) patients of which 7 (6%) developed bridging syndesmophytes. In 3 (3%) patients, new damage was present in ZA joints but not in vertebral bodies. Conclusions Scoring radiographic damage of ZA joints in AS patients is reliable. In this observational cohort of AS patients with active disease, damage of vertebral bodies at baseline and during 4 years of TNF-α blocking therapy was more common than damage of the ZA joints. Radiographic damage assessed with scoring the ZA joints contributed in only 3-4% of the patients in addition to the mSASSS. 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

SAT0343 Spinal Radiographic Progression during 6 Years of Tnf-Alpha Blocking Therapy in Patients with Ankylosing Spondylitis: Results from the GLAS Cohort

Background So far, inconsistent results have been reported regarding the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy on radiographic progression in ankylosing spondylitis (AS). Objectives To prospectively investigate spinal radiographic progression up to 6 years of TNF-α blocking therapy in patients with AS. Methods Consecutive outpatients from the Groningen Leeuwarden AS (GLAS) cohort, fulfilling the modified New York criteria for AS, with available radiographs before start of TNF-α blocking therapy and after 2, 4, and/or 6 years of follow-up were included. Radiographs of the cervical and lumbar spine were scored by two independent readers using the modified Stoke AS Score (mSASSS). Readers were blinded for patient characteristics and time sequence of radiographs. Generalized estimating equations were used to analyze spinal radiographic progression and clinical assessments over time within subjects and to calculate mean radiographic progression rate at group level. Spinal radiographic progression was compared between patients with high (TNF-α blocker use of ≥80% of follow-up time) and low TNF-α blocker compliance and between patients with (presence of ≥1 syndesmophyte) and without definite radiographic damage at baseline. Results 105 AS patients had mSASSS total scores available at baseline and after 2 years (n=81), 4 years (n=99) and/or 6 years (n=48) of follow-up. Of these patients, 73% were male, mean age was 42±11 years, median symptom duration was 16 years (range 1-47), 82% were HLA-B27 positive. Median baseline mSASSS was 12 (range 0-70) and 62 patients (59%) had definite radiographic damage at baseline. Overall, spinal radiographic progression was linear with a mean progression rate of 0.66 mSASSS units/year. Radiographic progression was comparable between patients with high and low TNF-α blocker compliance (mean 0.64 vs. 0.68 mSASSS units/year, p=0.34). Radiographic progression was significantly higher in patients with than without definite radiographic damage at baseline (mean 1.04 vs. 0.26 mSASSS units/year, p<0.001). TNF-α blocking therapy resulted in a clear and sustained improvement in disease activity, physical function, and quality of life. Conclusions This prospective longitudinal observational cohort study shows neither inhibition nor acceleration of radiographic progression over time at group level in AS patients who used TNF-α blocking therapy up to 6 years. Patients with no or limited spinal radiographic damage at baseline showed less radiographic progression compared to patients with more extensive radiographic damage. Whether early exposure to TNF-α blockers can halt radiographic progression remains to be demonstrated. 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, A. Spoorenberg Grant/research support: Abbott, Pfizer, Wyeth, Consultant for: Abbvie, Pfizer, UCB, E. Brouwer Grant/research support: Abbott, Pfizer, Wyeth, R. Bos Grant/research support: Pfizer, Consultant for: Pfizer, M. Efde: None declared, R. Chaudhry: None declared, N. Veeger: None declared, H. Bootsma: None declared, E. van der Veer: None declared, S. Arends Grant/research support: Abbott, Pfizer, Wyeth DOI 10.1136/annrheumdis-2014-eular.4385

SAT0354 Nsaid Use in Patients with Ankylosing Spondylitis Treated with and without Tnf-Alpha Blocking Therapy during 2-Year Follow-Up in Daily Clinical Practice

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<0.001). Disease activity was comparable between both groups after 24 months (median BASDAI 3.0 vs. 4.0, ASDAS 2.0 vs. 2.4, CRP 3 vs. 3; NS). 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<0.001) and 38% after 24 months (p<0.001). Of the 137 patients without TNF-α blocking therapy, 73% used NSAIDs at baseline and this proportion remained stable over time; 81% after 12 months (p=0.41) and 78% after 24 months (p=0.61). Similar results were found for the ASAS-NSAID index. NSAID use was comparable between both patient groups at baseline (p=0.18), whereas patients with TNF-α blocking therapy used significantly less NSAIDs after 24 months (p<0.001). 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