F. Maas

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.

Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands

Objectives To determine the prevalence of anticitrullinated protein antibodies (ACPAs) and their association with known rheumatoid arthritis (RA) risk factors in the general population. Methods Lifelines is a multidisciplinary prospective population-based cohort study in the Netherlands. Cross-sectional data from 40 136 participants were used. The detection of ACPA was performed by measuring anti-CCP2 on the Phadia-250 analyser with levels ≥6.2 U/mL considered positive. An extensive questionnaire was taken on demographic and clinical information, including smoking, periodontal health and early symptoms of musculoskeletal disorders. RA was defined by a combination of self-reported RA, medication use for the indication of rheumatism and visiting a medical specialist within the last year. Results Of the total 40 136 unselected individuals, 401 (1.0%) had ACPA level ≥6.2 U/mL. ACPA positivity was significantly associated with older age, female gender, smoking, joint complaints, RA and first degree relatives with rheumatism. Of the ACPA-positive participants, 22.4% had RA (15.2% had defined RA according to our criteria and 7.2% self-reported RA only). In participants without RA, 311 (0.8%) were ACPA-positive. In the non-RA group, older age, smoking and joint complaints remained significantly more frequently present in ACPA-positive compared with ACPA-negative participants. Conclusions In this large population-based study, the prevalence of ACPA levels ≥6.2 U/mL was 1.0% for the total group and 0.8% when excluding patients with RA. Older age, smoking and joint complaints were more frequently present in ACPA-positive Lifelines participants. To our knowledge, this study is the largest study to date on ACPA positivity in the general, mostly Caucasian population.

Clinical risk factors for the presence and development of vertebral fractures in patients with ankylosing spondylitis

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.

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

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.

Ultrasound Evaluation of the Entheses in Daily Clinical Practice during Tumor Necrosis Factor-alpha 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.

Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

Autoantibodies to nuclear structures are a hallmark of systemic lupus erythematosus (SLE), including autoantibodies to nuclear protein high mobility group box 1 (HMGB1). HMGB1 consists of three separate domains: box A, box B and an acidic tail. Recombinant box A acts as a competitive antagonist for HMGB1 and might be an interesting treatment option in SLE. However, antibodies to box A might interfere. Therefore, levels of anti‐box A were examined in SLE patients in association with disease activity and clinical parameters. Serum anti‐box A was measured in 86 SLE patients and 44 age‐ and sex‐matched healthy controls (HC). Serum samples of 28 patients with primary Sjögrens syndrome and 32 patients with rheumatoid arthritis were included as disease controls. Anti‐HMGB1 and anti‐box B levels were also measured by enzyme‐linked immunosorbent assay during quiescent disease [SLE Disease Activity Index (SLEDAI) ≤ 4, n = 47] and active disease (SLEDAI ≥ 5, n = 39). Anti‐box A levels in active SLE patients were higher compared to quiescent patients, and were increased significantly compared to HC and disease controls. Anti‐box A levels correlated positively with SLEDAI and anti‐dsDNA levels and negatively with complement C3 levels. Increased levels of anti‐box A antibodies were present in the majority of patients with nephritic (73%) and non‐nephritic exacerbations (71%). Antibodies to the box A domain of HMGB1 might be an interesting new biomarker, as these had a high specificity for SLE and were associated with disease activity. Longitudinal studies should be performed to evaluate whether these antibodies perform better in predicting an exacerbation, especially non‐nephritic exacerbations.