Ivette Essers

The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study

Objective To assess the incidence and risks of common extra-articular manifestations (EAMs), that is, acute anterior uveitis (AAU), psoriasis and inflammatory bowel disease (IBD), in patients with ankylosing spondylitis (AS) compared with population-based controls. Methods All incident patients with AS (n=4101) from the UK Clinical Practice Research Datalink (1987–2012) were matched with up to seven control subjects without AS by year of birth, sex and practice (n=28 591). Incidence rates, cumulative incidence rates and adjusted (adj) HRs for the development of EAMs were calculated, with time-dependent adjustments for age, sex, comorbidity and medication use. Results At diagnosis of AS, the proportion of patients with an EAM was 11.4% for AAU, 4.4% for psoriasis and 3.7% for IBD. Incidence rates of EAMs were 8.9/1000 person-years for AAU, 3.4/1000 person-years for psoriasis and 2.4 /1000 person-years for IBD in AS. The 20-year cumulative incidence was 24.5%, 10.1% and 7.5%, respectively. Risks of EAMs were 1.5-fold to 16-fold increased versus controls, with an adj HR of 15.5 (95% CI 11.6 to 20.7) for AAU, adj HR of 1.5 (95% CI 1.1 to 1.9) for psoriasis and adj HR of 3.3 (95% CI 2.3 to 4.8) for IBD. For psoriasis and IBD, the highest risks were found in the 1st years after diagnosis, while developing AAU continued to be increased also 10 years after diagnosis of AS. Conclusions The risk of, in particular AAU, but also of psoriasis and IBD, is significantly increased in patients with AS compared with controls. Hazard patterns are different for each of the EAMs.

Ankylosing spondylitis and risk of ischaemic heart disease: a population-based cohort study

Objective To investigate the incidence and risk of ischaemic heart disease (IHD) and acute myocardial infarction (AMI), including the role of non-steroidal anti-inflammatory drugs (NSAID), in patients with ankylosing spondylitis (AS) compared with population controls. Methods All patients with newly diagnosed AS (n=3809) from the British Clinical Practice Research Datalink (1987–2012) were matched with up to seven persons without AS by year of birth, gender and practice (n=26 197). Incidence rate ratios (IRR) and HRs for development of IHD and AMI were calculated. Stepwise analyses were performed adjusting for age, gender, comorbidity and drug use, including NSAIDs. Results At baseline, 4.3% of the patients had IHD and 1.8% had AMI compared with 3.4% and 1.4% of the controls, respectively. After exclusion of pre-existing IHD or AMI, the IRRs were 1.18 (95% CI 0.96 to 1.46) and 0.91 (95% CI 0.65 to 1.27) for IHD and AMI, respectively. Compared with controls, the age-gender adjusted HR for developing IHD was 1.20 (95% CI 0.97 to 1.48), and for AMI 0.91 (95% CI 0.65 to 1.28). In female patients, the risk of developing IHD was increased (HR 1.88, 95% CI 1.22 to 2.90), but after adjustment for all possible risk factors only a non-significant trend was found (HR 1.31, 95% CI 0.83 to 2.08). In particular, NSAID use explained this change (HR IHD adjusted for age-gender-NSAID use 1.57, 95% CI 0.99 to 2.48). Conclusions Female patients with AS had an increased age-adjusted risk of developing IHD, but after adjustment for NSAID use only a non-significant trend towards increased risk was found.

Gender-attributable differences in outcome of ankylosing spondylitis: long-term results from the Outcome in Ankylosing Spondylitis International Study

OBJECTIVES To investigate gender-attributable differences regarding clinical outcome [disease activity, physical function and quality of life (QoL)] and radiographic damage in patients with AS over time. METHODS Data from the Outcome in AS International Study were used. Disease activity was assessed by the BASDAI, ASDAS and CRP; physical function by BASFI; QoL by the Short Form-36, Ankylosing Spondylitis Quality of Life (ASQoL) score and European Quality Of Life scale; and radiographic damage by the modified Stoke AS Spine Score (mSASSS). Cross-sectional comparative analyses were done at baseline. Next, separate models were created to assess gender-attributable differences on each outcome measure over time using time-adjusted generalized estimating equations. RESULTS A total of 216 patients [154 (72.3%) males, mean age 43.6 years (s.d. 12.7), symptom duration 20.5 years (s.d. 11.8), mean follow-up duration 8.3 years (s.d. 4.1)] were included. At baseline, male compared with female patients had lower self-reported disease activity (BASDAI 3.2 vs 3.9, P = 0.03) but more radiographic damage (mSASSS 13.8 vs 6.5, P = 0.02). No significant gender-attributable differences in other clinical parameters were found. In multivariable analysis, male gender was significantly associated with a better ASQoL (B = -1.18, 95% CI: -2.17, -0.20, P = 0.02), and in a separate model with a higher mSASSS over time (B = 8.24, 95% CI: 4.38, 12.09, P < 0.01). CONCLUSION In this prospective cohort study, no gender-attributable differences in disease activity or physical function over time were found. However, radiographic damage was more severe in males. Furthermore, males had a better QoL over time.

Characteristics associated with the presence and development of extra-articular manifestations in ankylosing spondylitis: 12-year results from OASIS

OBJECTIVE The aim of this study was to identify characteristics associated with the presence and development of extra-articular manifestations (EAMs) in a prevalence cohort of patients with AS. METHODS Twelve-year follow-up data from the Outcome in Ankylosing Spondylitis International Study (OASIS) were used. In addition, medical charts were checked for the presence of acute anterior uveitis (AAU), IBD and psoriasis. Demographic, clinical and radiographic characteristics associated with the presence of (any) EAM at baseline or new development during follow-up were identified. RESULTS Two hundred and sixteen patients were included [mean age 43.6 years (s.d. 12.7), 154 (71%) men, mean symptom duration 20.5 years (s.d. 11.7), mean follow-up 8.3 years (s.d. 4.3)]. At baseline, 39 (18%) patients had AAU, 15 (7%) had IBD and 9 (4%) had psoriasis. The history of AAU was univariably associated with increased age [odds ratio (OR) 1.04 (95% CI 1.01, 1.07)], longer symptom duration [OR 1.05 (95% CI 1.02, 1.08)] and more radiographic damage [OR 1.02 (95% CI 1.00, 1.04)]. The history of psoriasis was associated with greater age [OR 1.05 (95% CI 1.00, 1.11)] and lower CRP [OR 0.77 (95% CI 0.59, 1.00)]. At follow-up, 27 patients developed a new EAM. Newly developed IBD was associated with a higher time-varying AS Disease Activity Score [hazard ratio (HR) 2.80 (95% CI 1.43, 5.52)], worse physical function [HR 1.40 (95% CI 1.09, 1.80)] and worse patient global well-being [HR 1.46 (95% CI 1.10, 1.93)]. Newly developed AAU was associated with an elevated time-varying CRP [HR 1.02 (95% CI 1.01, 1.04)]. CONCLUSION Development of EAMs was infrequent in this cohort, despite relatively long follow-up. In particular, markers of disease activity were associated with the development of IBD.

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.

Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages

Introduction The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Methods Translation and cross-cultural adaptation has been carried out following the forward–backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. Results The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option ‘not applicable’ was added to two items of the ASAS HI to improve appropriateness. Discussion This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.

Efficacy of upper limb strengthening in children with Cerebral Palsy: A critical review

OBJECTIVE This review focuses on the effects of strengthening interventions of the upper limb in children with Cerebral Palsy (CP). The strengthening intervention studies were divided in two categories: those based on stand-alone strength training, and those on strength training combined with other interventions. DATA SOURCES AND EXTRACTION A search in all relevant databases was performed. DATA SYNTHESIS Six articles were included: three randomized controlled trials (RCTs), two clinical trial (CT) and one case study. Effect sizes of strength training on muscle strength and function of the upper limb were calculated. CONCLUSION There are no coherent recommendations for strength training, based on these studies. The causes include too much variety of types of training, level of intensity and duration. All of the reported upper limb strength training studies found an increase in muscle strength. In addition, the quality of these studies was not high. More RCTs on strength training according to the official strength training guidelines are necessary to assess the impact and potential of strength training of the upper limb to improve the daily activities and participation in children with CP.

FRI0117 Disease Activity is Associated with Development of Inflammatory Bowel Disease in Ankylosing Spondylitis: 12-Year Results from Oasis

Background Little is known about the characteristics of patients with ankylosing spondylitis (AS) who develop extra-articular manifestations (EAM), such as acute anterior uveitis (AAU), inflammatory bowel disease (IBD), and psoriasis. Objectives To identify characteristics associated with the development of EAMs in a prevalence cohort of patients with AS. Methods 12-Year follow-up data from patients included in the Outcome in AS International Study (OASIS) were used. Additionally, two independent extractors checked medical charts for the presence of AAU, IBD or psoriasis. At baseline, logistic regression was performed to identify demographic, clinical, and radiographic characteristics associated with the presence of any EAM. Cox regression and survival analyses were performed to identify characteristics associated with development of any EAM over time, using both characteristics at baseline and at the time of diagnosis of an EAM. Results 216 patients were included (mean age 43.6 years (SD 12.7), 154 (71%) men, mean symptom duration 20.5 years (SD 11.7), 174 (85%) HLA-B27 positive and mean follow-up 8.3 years (SD 4.3)). At baseline, 59 (27%) patients had any EAM, of which 39 (18%) AAU, 15 (7%) IBD, and 9 (4%) psoriasis. Four patients (2%) had more than one EAM. At baseline, patients with AAU compared with patients without AAU were older (49.1 vs 42.4 years, p<0.01), had a longer symptom duration (25.9 vs 19.3 years, p<0.01), and more radiographic damage (modified Stoke AS Spinal Score 16.9 vs 10.6, p=0.03). Patients with psoriasis compared with patients without psoriasis were older (51.3 vs 43.3 years, p=0.05). There were no differences between patients with and without IBD. During follow-up 27 patients developed a new EAM; 19 AAU, 9 IBD, and 5 psoriasis with incidence rates of 0.9%, 0.4%, and 0.02% per year, respectively. The following characteristics at the time of diagnosis of the EAM were associated with the development of IBD in univariable analysis: ASDAS (Hazard Ratio [HR] 2.81, 95% Confidence Interval [95% CI] 1.43-5.53), BASDAI (HR 1.47 95% CI 1.09-1.98), CRP (HR 1.02, 95% CI 1.00-1.05), BASFI (HR 1.40, 95% CI 1.09-1.80) and BAS-G (HR 1.46, 95% CI 1.10-1.96). Moreover, CRP was weakly associated with the development of AAU (HR 1.02, 95% CI 1.01-1.04). No significant associations with development of psoriasis were found. Conclusions At baseline, a substantial number of patients already had an EAM in this prevalence cohort with relatively long symptom duration. Development of new EAMs was infrequently observed. In particular disease activity, but also physical function and patient global assessment, were associated with development of IBD. CRP was associated with the development of AAU. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1857

THU0090 Cardiovascular Morbidity in Patients with Ankylosing Spondylitis: A Population-Based Cohort Study

Background It is well recognized that rheumatoid arthritis is an independent risk factor for cardiovascular (CV) disease. For ankylosing spondylitis (AS), the literature on this risk is relatively scarce, and shows conflicting results. Furthermore, these studies did not explore the role of non-steroidal anti-inflammatory drugs (NSAIDs) use. Objectives To examine the incidence and risk of ischemic heart disease (IHD) and acute myocardial infarction (AMI) in patients with AS compared with population-based controls, and explore the role of recent NSAID use. Methods All incident patients with AS from the UK Clinical Practice Research Datalink (1987-2012) were matched with up to 7 persons without AS by year of birth, sex and practice. Incidence rates, cumulative incidence rates and hazard ratios (HR) for the development of IHD and AMI were calculated, with time-varying adjustments for age, sex, comorbidity and drug use. When further exploring the role of NSAIDs on the risk of IHD, patients with AS were stratified according to the use of coxibs, naproxen or other traditional NSAIDs in the previous 3 months. Results In total, 3,809 patients with AS (mean age at index date 43.7 years, 70.5% male, median duration of follow-up 6.6 years) were matched with 26,197 control subjects. At baseline, 4.3% of the patients had IHD compared with 3.4% of the controls (p-value<0.01), and 1.8% of the patients had AMI compared with 1.4% of the controls (p-value=0.02). After excluding patients with IHD and/or AMI at baseline, the incidence rates were 1.2/1000 person years (pys) and 0.9/1000 pys for IHD and AMI, respectively. The age-gender adjusted (adj.) HR of developing IHD was 1.2 (95% Confidence interval [CI] 1.0-1.5), and for AMI 0.9 (95% CI 0.7-1.3). After statistical adjustment for recent use of NSAIDs, the increased risk of IHD disappeared (adj. HR 1.1 95% CI 0.9-1.3). In the fully adjusted model, the risk remained almost unchanged (adj. HR 1.0, 95% CI 0.8-1.3). In patients with AS, stratification according to the use of coxibs, naproxen or other NSAIDs, showed that exposure to NSAIDs other than naproxen or coxibs increased the risk of IHD to 1.5 (95% CI 1.1-2.1) compared with controls irrespective of their NSAID use. However, within patients with AS this risk was not different from AS patients who did not use NSAIDs other than naproxen or coxibs (p=0.17). Conclusions Patients with AS seemed at increased risk of developing IHD, but this effect could be attributed to their recent NSAID use. Although it cannot be excluded that NSAID use is (partly) a reflection of disease activity, rheumatologists should carefully balance the beneficial effects of NSAIDs and the increased risk of IHD. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.1853