Patients' Perspectives on Axial Pain in Relation to Inflammation and Structural Damage in a Large Cohort of Axial Spondyloarthritis Patients.

OBJECTIVE: The objective of this study was to explore to what extent patients with axial spondyloarthritis (axSpA) link experienced pain in the neck, back, and hips to inflammation and/or structural damage. METHODS: Patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort visiting the outpatient clinic between 2016 and 2019 filled out two additional questions in relation to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 2: (1) "To what extent do you think the pain you experience in your neck, back, and hips is related to inflammation caused by axSpA?" and (2) "To what extent do you think the pain you experience in your neck, back, and hips is related to damage of the spine and joints caused by axSpA?" Answers had to be depicted on a numeric rating scale from 0 (none) to 10 (very much); a difference of ≥2 points between the scores of these questions was considered clinically relevant in favor of the highest scoring question. RESULTS: A total of 688 patients with axSpA (24% with nonradiographic axSpA [nr-axSpA]) were included (62% male, mean ± SD age 48 ± 14 years, and mean ± SD Ankylosing Spondylitis Disease Activity Score [ASDAS] 2.3 ± 1.0). Seventy-five percent of patients could not link the origin of their pain, 15% linked axial pain predominantly to inflammation, and 10% linked axial pain predominantly to damage. Patients in the inflammation group were younger, had shorter symptom duration, were more frequently diagnosed with nr-axSpA, had higher ASDASCRP , had more often elevated CRP levels, had fewer comorbidities, had better spinal mobility, and had less spinal radiographic damage. CONCLUSION: In our large observational cohort, the majority of patients with axSpA could not differentiate the origin of experienced axial pain. If patients were able to link axial pain to clinical inflammation or damage, it was in concordance with clinical assessments and radiographic outcome, which may be helpful in establishing the origin of pain and supporting better patient-centered treatment decisions.

Baseline serum biomarkers of inflammation, bone turnover and adipokines predict spinal radiographic progression in ankylosing spondylitis patients on TNF inhibitor therapy.

OBJECTIVE: To analyze whether biomarker levels at baseline or their change after 3 months or 2 years predict radiographic spinal progression in ankylosing spondylitis (AS) patients treated with TNF-α inhibitors (TNFi). METHODS: 137 AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included before starting TNFi. Serum biomarkers were measured at baseline, 3 months and 2 years: Markers of inflammation (calprotectin, matrix metalloproteinase-3, vascular endothelial growth factor), bone turnover markers (bone-specific alkaline phosphatase, serum C-terminal telopeptide fragments of type I collagen (sCTX), osteocalcin, osteoprotegerin, procollagen type I and II N-terminal propeptide, sclerostin) and adipokines (high-molecular-weight adiponectin, leptin, visfatin). Spinal radiographs were scored at baseline, 2 and 4 years. Logistic regression was performed to examine the association between biomarker values and radiographic spinal progression, adjusting for known risk factors for radiographic progression. RESULTS: Baseline calprotectin and visfatin levels were associated with mSASSS progression ≥2 points (OR 1.195 [95%CI 1.055-1.355] and 1.465 [1.137-1.889], respectively), while calprotectin was also associated with new syndesmophyte formation after 2 years (OR 1.107 [1.001-1.225]). Baseline leptin level was associated with mSASSS progression ≥4 points after 4 years (OR 0.614 [0.453-0.832]), and baseline sCTX level with syndesmophyte formation after 4 years (OR 1.004 [1.001-1.008]). Furthermore, change of visfatin and leptin levels over the first 2 years showed significant association with radiographic progression after 4 years. CONCLUSION: Independent of known risk factors, serum levels of biomarkers at baseline are able to predict radiographic spinal progression over 2 and 4 years in AS patients on TNFi therapy.

The mSQUASH; a valid, reliable and responsive questionnaire for daily physical activity in patients with axial spondyloarthritis.

AIM: Adaptation of the Short QUestionnaire to Assess Health-enhancing physical activity (SQUASH) in order to improve measurement properties in axSpA patients. METHODS: The original SQUASH was adapted using a qualitative stepwise approach with in-depth interviews including healthcare professionals and patients. Content validity was explored by comparing modified-SQUASH (mSQUASH) and original SQUASH. Next, mSQUASH was validated according to the OMERACT filter. International Physical Activity Questionnaire (IPAQ) was used as comparator and tri-axial accelerometer as gold standard for criterion validity and classification accuracy of intensity. Construct validity was assessed using Spearman correlations with clinical outcome assessments. For test-retest reliability, intra-class correlation coefficients (ICCs) were calculated. Responsiveness was assessed using standardized response mean (SRM), stratified by Anchor method. RESULTS: The mSQUASH measured a systematically higher activity count and had less missing values (8% vs. 16%) then SQUASH. mSQUASH correlated better with accelerometer compared to IPAQ (ρ = 0.60 vs. ρ = 0.34). Accelerometer measured most activity in light intensity, whereas mSQUASH and IPAQ predominately measured moderate intensity. Correlations with ASDAS, BASDAI, BASFI and ASQoL were better for mSQUASH then IPAQ. Test-retest reliability was good in both questionnaires. In contrast to IPAQ, responsiveness was in correspondence with self-reported changes in physical activity for mSQUASH (SRM -0.84 for improvement and 0.88 for decrease). The average completion time of the mSQUASH was 7 minutes. CONCLUSIONS: The development of the mSQUASH resulted in an easy applicable, valid, reliable and responsive questionnaire for the assessment of daily physical activity in axSpA patients, which can be used in research and daily clinical practice.

Bone mineral density improves during 2 years of treatment with bisphosphonates in patients with ankylosing spondylitis.

AIMS: To evaluate whether 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements has an effect on lumbar spine and hip bone mineral density (BMD) in ankylosing spondylitis (AS) patients starting tumour necrosis factor-α inhibitors or receiving conventional treatment. Secondly, to explore the development of radiographic vertebral fractures. METHODS: Patients from the Groningen Leeuwarden AS cohort receiving bisphosphonates based on clinical indication and available 2-year follow-up BMD measurements were included. BMD of lumbar spine (L1-L4) and hip (total proximal femur) were measured using dual-energy X-ray absorptiometry. Spinal radiographs (Th4-L4) were scored for vertebral fractures according to the Genant method. RESULTS: In the 20 included patients (median 52 years, 14 males), lumbar spine and hip BMD Z-scores increased significantly; median from -1.5 (interquartile range [IQR] -2.2 to 0.4) to 0.1 (IQR -1.5 to 1.0); P < .001 and median from -1.0 (IQR -1.6 to -0.7) to -0.8 (IQR -1.2 to 0.0); P = .006 over 2 years, respectively. In patients also treated with tumour necrosis factor-α inhibitors (n = 11), lumbar spine and hip BMD increased significantly (median 2-year change +8.6% [IQR 2.4 to 19.6; P = .009] and +3.6% [IQR 0.7-9.0; P = .007]). In patients on conventional treatment (n = 9), lumbar spine BMD increased significantly (median 2-year change +3.6%; IQR 0.7 to 9.0; P = .011) and no improvement was seen in hip BMD (median -0.6%; IQR -3.1 to 5.1; P = .61). Overall, younger AS males with limited spinal radiographic damage showed most improvement in lumbar spine BMD. Four mild radiographic vertebral fractures developed in 3 patients and 1 fracture increased from mild to moderate over 2 years in postmenopausal women and middle-aged men. CONCLUSION: This explorative observational cohort study in AS showed that 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements significantly improves lumbar spine BMD. Mild radiographic vertebral fractures still occurred.

High prevalence of hip involvement and decrease in inflammatory ultrasound lesions during tumour necrosis factor-α blocking therapy in ankylosing spondylitis.

OBJECTIVES: To assess the prevalence of clinical, US and radiographic hip involvement in AS patients with active disease and to explore the associations between these assessments. Furthermore, to evaluate the effect of 6 months of TNF-α blocking therapy on tender and inflammatory power Doppler US lesions of hip joints. METHODS: Consecutive AS patients starting TNF-α blocking therapy were evaluated for hip joint involvement. At baseline, patient-reported history of hip involvement was assessed and radiographic evaluation (BASRI-hip) was performed. Clinical examination (tender hip joints) and US examination took place before and after 6 months of treatment. RESULTS: Of the 111 included patients, 20% reported a history of hip involvement. At baseline, tender hip joints were present in 23% of patients. US examination showed inflammatory lesions in 17% of patients, of which 74% had positive power Doppler. Structural lesions were present in 20% of patients, of which 55% had osteophytes. Structural radiographic damage was seen in 10% of patients. Highest concordance was found between history of hip involvement and radiographic hip involvement (phi coefficient 0.333). After 6 months of TNF-α blocking therapy, significant decrease was found in tender hip joints (from 29 to 11), total number of inflammatory US lesions (from 29 to 9) and positive power Doppler (from 22 to 6). CONCLUSION: The prevalence rate of hip involvement in AS patients varies from 10 to 23%, depending on the type of hip assessment. TNF-α blocking therapy significantly improved tender hip joints, and inflammatory US lesions including positive power Doppler.

Although female patients with ankylosing spondylitis score worse on disease activity than male patients and improvement in disease activity is comparable, male patients show more radiographic progression during treatment with TNF-α inhibitors.

BACKGROUND: The clinical presentation of ankylosing spondylitis (AS) differs between genders. Our aim was to investigate differences in disease activity, disease outcome and treatment response between male and female AS patients before and after starting tumor necrosis factor (TNF)-α inhibitors in daily clinical practice. METHODS: Patients from the Groningen Leeuwarden AS (GLAS) cohort who started TNF-α inhibitors and who had visits at baseline and after 3 months and/or 2years of follow-up were included. RESULTS: Of 254 included AS patients, 69% were male. At baseline, female patients scored significantly higher on BASDAI, ASDAS, and tender entheses than male patients. In contrast, CRP, swollen joints, and history of extra-articular manifestations were comparable between genders. Women experienced significantly worse physical function and QoL, whereas men showed significantly more kyphosis and spinal radiographic damage. After 3 months and 2years of follow-up, all clinical assessments improved significantly, with comparable mean change scores for female and male patients; mean 2-year change in BASDAI -2.7 vs. -2.7, ASDAS -1.50 vs. -1.68, tender entheses -2.4 vs. -1.4, CRP -8 vs. -8, BASFI -2.2 vs. -2.1 and ASQoL -5 vs. -4, respectively. Radiographic progression was significantly higher in male patients. Female patients switched more frequently to another TNF-α inhibitor during 2years of follow-up (32% vs. 14%). CONCLUSION: Although female patients experienced higher disease activity, worse physical function and quality of life, and switched TNF-α inhibitors more often, clinical improvement during treatment with TNF-α inhibitors was comparable between genders. However, male patients showed more radiographic spinal damage after 2years.

Ankylosing spondylitis disease activity score is related to NSAID use, especially in patients treated with TNF-α inhibitors.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are regarded as the cornerstone of conventional treatment for AS. However little is known about concomitant NSAID use during treatment (with TNF-α inhibitors) in daily clinical practice. METHODS AND FINDINGS: Consecutive patients from the GLAS cohort were included. NSAID use and ASAS-NSAID index were evaluated at group level and at individual patient level during 52 weeks of follow-up. Analyses were stratified for treatment regimen. Generalized estimating equations (GEE) was used to evaluate NSAID use in relation to assessments of disease activity over time. In patients starting TNF-α inhibitors (n = 254), 79% used NSAIDs at baseline and this proportion decreased significantly to 38% at 52 weeks. ASAS-NSAID index also decreased significantly from median 65 to 0. In patients on conventional treatment (n = 139), 74% used NSAIDs at baseline with median ASAS-NSAID index of 50 and this remained stable during follow-up. At each follow-up visit, approximately half of the patients changed their type or dose of NSAIDs. GEE analysis over time showed that NSAID use was associated with AS disease activity score (p<0.05). This relation was more pronounced in patients treated with TNF-α inhibitors compared to conventional treatment (B = 0.825 vs. B = 0.250). CONCLUSIONS: In this observational cohort of established AS patients, there was no difference in baseline NSAID use between patients with and without indication for TNF-α inhibitors. NSAID use decreased significantly after starting TNF-α inhibitors. During conventional treatment, NSAID use remained stable at group level. However, NSAID use changed frequently at individual patient level and was significantly associated with disease activity.

Ankylosing spondylitis patients at risk of poor radiographic outcome show diminishing spinal radiographic progression during long-term treatment with TNF-α inhibitors.

OBJECTIVE: To investigate the influence of patient characteristics on the course of spinal radiographic progression in a large prospective longitudinal cohort study of ankylosing spondylitis (AS) patients treated long-term with TNF-α inhibitors. METHODS: Consecutive patients from the Groningen Leeuwarden AS (GLAS) cohort starting TNF-α inhibitors with spinal radiographs at least available at baseline and 6 years of follow-up were included. Radiographs were scored using mSASSS by two independent readers. Generalized estimating equations (GEE) were used to explore the associations between baseline characteristics and spinal radiographic progression. The course of radiographic progression in patients with and without risk factors for poor radiographic outcome was investigated using different time models (linear and non-linear). Single linear imputation was used in case of missing radiographic data at the intermediate (2 or 4 years) follow-up visits. RESULTS: 80 AS patients were included with mean baseline mSASSS 8.7±13.3. Baseline syndesmophytes, male gender, older age, longer symptom duration, smoking, and higher BMI were significantly associated with more radiographic damage over time. GEE analysis in patients with these risk factors revealed that radiographic progression followed a non-linear course with mean mSASSS progression rates reducing from max. 2.8 units over 0-2 years to min. 0.9 units over 4-6 years. The GEE model revealed a linear course with overall very low progression (≤1 mSASSS units/2yrs) in patients without risk factors. Complete case analysis in 53 patients showed similar results. CONCLUSION: AS patients at risk of poor radiographic outcome showed the highest but diminishing spinal radiographic progression during long-term treatment with TNF-α inhibitors.

Incorporating assessment of the cervical facet joints in the modified Stoke ankylosing spondylitis spine score is of additional value in the evaluation of spinal radiographic outcome in ankylosing spondylitis.

BACKGROUND: To aim was to investigate the additional value of incorporating the de Vlam cervical facet joint score in the modified ankylosing spondylitis (AS) spine score (mSASSS) for the evaluation of spinal radiographic outcome in AS. METHOD: Baseline and 4-year radiographs from 98 consecutive patients from the Groningen Leeuwarden AS (GLAS) cohort, who had AS treated with TNF-α inhibitors, were scored by two readers; the vertebral bodies were assessed according to the mSASSS (0-72) and cervical facet joints (C2-C7) were assessed according to the method of de Vlam (0-15). The combined AS spine score (CASSS) was calculated as the sum of both total scores (range 0-87) and compared with the original mSASSS according to three aspects of the Outcome Measures in Rheumatology Clinical Trials (OMERACT) filter: feasibility, discrimination, and truth. RESULTS: Feasibility: the CASSS was calculated in 91% of the patients. No additional radiographs were necessary and the assessment took only a few extra minutes. Discrimination: both scoring methods had excellent inter-observer reliability (intra-class correlation coefficient (ICC) status scores >0.99, progression scores 0.92). Incorporating the cervical facet joints did not result in an increase in measurement error. The CASSS detected more patients with definite damage (61% vs. 57%) and definite progression (55% vs. 48%). Truth: higher CASSS scores at baseline and higher progression scores were seen in 41 (46%) and 22 (25%) patients, respectively. Cervical rotation correlated better with cervical CASSS than with cervical mSASSS (Spearman's rho = 0.68 vs. 0.59). CONCLUSIONS: The CASSS is a relevant and easy modification of the mSASSS. It captures more patients with AS who have spinal radiographic damage and progression, which is of great additional value in the evaluation of radiographic outcome in this heterogeneous and overall slowly progressing disease.

Ultrasound Evaluation of the Entheses in Daily Clinical Practice during Tumor Necrosis Factor-α Blocking Therapy in Patients with Ankylosing Spondylitis.

OBJECTIVE: To assess structural and inflammatory ultrasound (US) lesions of entheses in ankylosing spondylitis (AS) patients with active disease and to evaluate inflammatory lesions after 6 months of tumor necrosis factor (TNF-α) blocking therapy, in daily clinical practice. METHODS: Consecutive patients with AS were clinically evaluated and underwent US examination of 9 bilateral entheses before and after 6 months of TNF-α blocking therapy. US examination included the following as inflammatory lesions: bone erosions/cortical irregularities, enthesophytes, calcifications as structural lesions; adjacent bursitis, effusion, increased tendon hypoechogenicity or thickness; and positive power Doppler (PD) signal. RESULTS: At baseline, 105 (95%) of 111 included patients showed US abnormalities. Structural lesions were seen in 74 patients (67%) and inflammatory lesions in 88 (79%). Enthesophytes and positive PD signal were the most prevalent structural and inflammatory lesions, respectively. Most lesions were found at the lower extremities. Additionally, inflammatory lesions occurred at the lateral epicondyle of the elbow. Patients with structural lesions at baseline were significantly older, had longer disease duration, higher modified Stoke AS Spine score, and higher C-reactive protein. Individually, there was a great diversity in changes of inflammatory entheseal lesions during treatment, but on the group level no significant decrease was found. CONCLUSION: This prospective observational cohort study in daily clinical practice shows a high prevalence of structural and inflammatory US lesions in AS patients with longstanding and active disease. Positive PD signal was the most common inflammatory feature. No significant change in inflammatory US lesions was found after 6 months of TNF-α blocking therapy.

Radiographic damage and progression of the cervical spine in ankylosing spondylitis patients treated with TNF-α inhibitors: Facet joints vs. vertebral bodies.

OBJECTIVES: To investigate radiographic damage and 4-year progression of the cervical facet joints in a prospective observational cohort of AS patients treated with TNF-α inhibitors, to compare this with damage and progression of the cervical vertebral bodies, and to study the relation with patient characteristics and clinical outcome. METHODS: Patients from the Groningen Leeuwarden AS (GLAS) cohort starting TNF-α inhibitors with baseline and 4-year radiographs were included. Cervical facet joints and vertebral bodies were scored by two independent readers according to the method of de Vlam and mSASSS, respectively. RESULTS: At baseline, 25 of 99 (25%) AS patients had partial or complete ankylosis of the cervical facet joints, whereas 51 (52%) patients had non-bridging or bridging syndesmophytes of cervical vertebral bodies. During 4 years, 13 (13%) patients developed new (partial) ankylosis of the facet joints, whereas 26 (26%) developed new (bridging) syndesmophytes. Facet joint damage and progression without involvement of the vertebral bodies were seen in 5 (5%) and 8 (8%) patients, respectively. Damage of facet joints was associated with longer disease duration, history of IBD/uveitis/psoriasis, higher disease activity, larger occiput-to-wall distance, higher mSASSS, and presence of syndesmophytes. Progression of the facet joints was associated with larger occiput-to-wall distance and more facet joint damage at baseline. CONCLUSIONS: Cervical facet joints were frequently involved in AS. During 4 years of TNF-α blocking therapy, 13% of the patients showed radiographic progression of cervical facet joints of which the majority did not show progression of vertebral bodies.

Clinical Risk Factors for the Presence and Development of Vertebral Fractures in Patients With Ankylosing Spondylitis.

INTRODUCTION: 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 2 readers according to the method of Genant et al. Differences in baseline characteristics between patients with and without radiographic vertebral fractures were explored. RESULTS: Of 292 included AS patients, 59 (20%) had radiographic vertebral fractures at baseline, 15 (6%) developed new fractures, and 7 (2%) showed an increase in the severity of existing fractures during 2 years of follow-up. Most fractures were mild and located in the midthoracic and thoracolumbar region of the spine. The presence of vertebral fractures was significantly associated with older age, higher body mass index, longer smoking duration, larger occiput-to-wall distance, more spinal radiographic damage, and lower hip bone mineral density (BMD). The development of new or progressive vertebral fractures was also associated with older age and low BMD. Patients using nonsteroidal antiinflammatory drugs (NSAIDs) at baseline showed less prevalent and incident vertebral fractures. CONCLUSION: In this large AS cohort in daily clinical practice, radiographic vertebral fractures were frequently present in AS, 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 fractures risk.

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

OBJECTIVE: 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. METHODS: Consecutive patients from the Groningen Leeuwarden AS cohort starting TNF inhibitors between 2004 and 2012 were included. Baseline and biannual radiographs were randomized with radiographs of TNF-naive AS patients and scored in chronologic order according to modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The course of radiographic progression (linear or nonlinear) was investigated using generalized estimating equations. Primary analysis was performed in patients with complete data over 4, 6, and 8 years of followup. Sensitivity analysis was performed after single linear imputation of missing radiographic data and after adjusting for patient characteristics with possible influence on radiographic progression. RESULTS: At baseline, median mSASSS of 210 included AS patients was 2.8 (interquartile range 0.0-12.0), mean ± SD mSASSS 10.0 ± 15.5. During the first 4 years, radiographic progression followed a linear course (estimated mean progression rate was 1.7 for 0-2 and 2-4 years). A deflection from a linear course was found in patients with complete and imputed data over 6 and 8 years. The estimated mean 2-year progression rate reduced from 2.3 to 0.8 in patients with complete 8-year data. The same pattern was found after adjustment for baseline mSASSS scores, presence of syndesmophytes, sex, HLA-B27 status, age, symptom duration, smoking duration, body mass index, disease activity, and nonsteroidal antiinflammatory drug use. CONCLUSION: This observational cohort study in AS patients receiving long-term TNF inhibitors showed a reduction in spinal radiographic progression after more than 4 years of followup.

Radiographic vertebral fractures develop in patients with ankylosing spondylitis during 4 years of TNF-α blocking therapy.

OBJECTIVES: To determine the prevalence and incidence of radiographic vertebral fractures in ankylosing spondylitis (AS) patients treated with TNF-α blocking therapy for 4 years and to explore the relationship with patient characteristics, clinical assessments, radiographic damage, and bone mineral density (BMD). METHODS: This study included consecutive AS patients with active disease from the Groningen Leeuwarden AS (GLAS) cohort treated with TNF-α blocking therapy for 4 years and with available thoracic and lumbar radiographs at baseline and at 4 years. Vertebral fractures were assessed by two readers (mild: ≥20-<25%, moderate: ≥25-<40%, severe: ≥40% reduction in vertebral height). RESULTS: In 27 of 105 (26%) AS patients, radiographic vertebral fractures were observed at baseline. These patients were significantly older, had larger occiput-to-wall distance, and more spinal radiographic damage. During 4 years of TNF-α blocking therapy, 21 (20%) patients developed at least one new fracture. Older age, smoking, higher BASFI, low lumbar spine BMD (Z-score ≤-2), presence of moderate vertebral fractures, and use of anti-osteoporotic treatment at baseline were associated with the development of new fractures. Most fractures were mild and occurred in the thoracic spine. The improvement in lateral spinal mobility and lumbar spine BMD during treatment was significantly less in patients with new fractures (median change of 0.8 vs. 2.8 cm and 0.3 vs. 0.8 Z-score, respectively). CONCLUSIONS: The prevalence of radiographic vertebral fractures was high in AS patients with active disease. Although clinical assessments and BMD improved significantly, new vertebral fractures still developed during 4 years of TNF-α blocking therapy.

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/m(2)), overweight (BMI ≥ 25 to < 30 kg/m(2)), and obese (BMI ≥ 30 kg/m(2)). 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.