R.N. Chaudhry

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.

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

FRI0116 Prevalence of Vertebral Fractures and the Relation to Clinical and Radiological Outcome in Ankylosing Spondylitis Patients with Active Disease

Background Ankylosing spondylitis (AS) is characterized by the combination of inflammation, excessive bone formation, and bone loss in the axial skeleton. This excessive bone loss may lead to the occurrence of vertebral fractures (VF). Objectives To investigate the prevalence and distribution of VF and their relation to clinical and radiological outcome in AS patients with active disease. Methods All consecutive patients from the Groningen Leeuwarden AS (GLAS) cohort who visited the outpatient clinic between November 2004 and June 2011 with active disease (Bath AS Disease Activity Index (BASDAI) ≥4 and/or expert opinion) and available spinal radiographs were included. Patients fulfilled the modified New York criteria for AS. Radiographs of the thoracic and lumbar spine were scored using the method of Genant et al., a semiquantitative technique evaluating anterior, middle, and posterior heights of vertebrae Th4 to L4. VF were defined based on reduction in vertebral height: grade 1 (mild): 20-25% reduction; grade 2 (moderate): 25-40% reduction; and grade 3 (severe): >40% reduction. Radiographs of the cervical and lumbar spine were scored for spinal radiographic damage using the modified Stoke AS Score (mSASSS). All radiographs were scored by two independent readers blinded for patient characteristics. Results 205 AS patients were included; 67% were male, mean age was 42±11 years, median symptom duration was 15 years (range 1-53), 80% were HLA-B27 positive, mean BASDAI was 6.1±1.6, mean ASDAS was 3.8±0.8, and median mSASSS was 11.2 (range 0-72). In total, 2518 vertebrae could be scored and 110 VF (4.4%) were found. Of these VF, 74 were scored grade 1, 34 grade 2, and 2 grade 3. 84% of VF occurred in the thoracic spine (Figure 1). The average number of VF per patient was 1.8. Sixty of 205 patients (29%) showed at least 1 VF, of which 33 patients had 1 VF, 16 patients 2 VF, and 11 patients more than 2 VF. Patients with VF were older (mean age 46 vs. 41 years, p<0.01), were more frequently male (77% vs. 63%, p=0.066), had larger occiput to wall distance (median 5.0 vs. 3.5 cm, p<0.05), and had significantly more spinal radiographic damage (median mSASSS 15.6 vs. 9.9, p<0.05) compared to patients without VF. Figure 1. Locations and severity of 110 vertebral fractures in patients with AS. Conclusions In our cross-sectional observational cohort, the prevalence of VF is 29% in AS patients with active disease. Most VF are located in the middle and low thoracic spine. The presence of VF is associated with older age, male gender, increased thoracic kyphosis, and more spinal radiographic damage. Further longitudinal research is needed to investigate the influence of treatment (e.g. NSAIDs, TNF-α blockers) on the development of new VF in AS. 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.4298