J. C. van Denderen

Immunogenicity does not influence treatment with etanercept in patients with ankylosing spondylitis.

Background: Immunogenicity, specifically the onset of antibodies against tumour necrosis factor (TNF) blocking agents, seems to play an important role in non-response to treatment with these drugs. Objectives: To assess the relation of clinical response of ankylosing spondylitis (AS) to etanercept with etanercept levels, and the presence of antibodies to etanercept. Methods: Patients with AS were treated with etanercept 25 mg twice weekly, according to the international Assessment in Ankylosing Spondylitis (ASAS) working group consensus statement. Sera were collected at baseline and after 3 and 6 months of treatment. Clinical response was defined as a 50% improvement or as an absolute improvement of 2 points on a (0–10 scale) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. Functional etanercept levels were measured by a newly developed ELISA, measuring the binding of etanercept to TNF. Antibodies against etanercept were measured with a two-site assay and antigen binding test. Clinical data were used to correlate disease activity with serum etanercept levels. Results: In all, 53 consecutive patients were included. After 3 months of treatment 40 patients (76%) fulfilled the response criteria. Mean etanercept levels were 2.7 mg/litre and 3.0 mg/litre after 3 and 6 months respectively. Characteristics and etanercept levels of responders and non-responders were similar. No antibodies to etanercept were detected with any of the assays. Conclusion: Etanercept levels of responders and non-responders were similar and no antibodies to etanercept were detected with any of the assays. This study indicates that etanercept is much less immunogenic compared with the other TNF-blocking agents.

Increased disease activity is associated with a deteriorated lipid profile in patients with ankylosing spondylitis.

Background: Cardiovascular mortality is increased in patients with ankylosing spondylitis. A possible explanation might be a more prevalent atherogenic lipid profile in patients with ankylosing spondylitis than in the general population. It has been postulated that inflammation deteriorates the lipid profile, thereby increasing cardiovascular risk. Objective: To explore the association between disease activity and lipid profile in patients with ankylosing spondylitis. Methods: Disease activity parameters for ankylosing spondylitis and lipid levels (total cholesterol, high-density lipoprotein cholesterol (HDLc) and triglycerides) were measured in 45 patients with ankylosing spondylitis for 6 months after starting treatment with leflunomide or placebo. Findings in this treatment group were compared with those in 10 patients with ankylosing spondylitis treated with etanercept. A specialised regression model, adjusting for repeated measurements, age and sex, was used to assess the influence of the disease activity variables on the lipid levels. Results: Multilevel regression analyses showed significant associations between disease activity parameters and lipid levels—for instance, an increase of 30 mm at the end of the first hour in erythrocyte sedimentation rate was associated with a decrease of about 6% in total cholesterol level and a decrease of about 11% in HDLc levels. Similar significant associations were found between other disease activity parameters and lipid levels. Conclusion: Increase in disease activity was associated with decreases in lipid levels. The decrease in HDLc levels tended to be almost twice as large as the decrease in total cholesterol levels, resulting in a more atherogenic lipid profile. Hence, effective treatment of disease activity in patients with ankylosing spondylitis may lower the cardiovascular risk by improving the lipid profile.

Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis

Objective: To assess the efficacy and safety of leflunomide in active ankylosing spondylitis (AS) compared with placebo in a 24 week pilot study. Methods: In a single centre randomised, double blind, placebo controlled study, 45 patients with active AS were randomised to either leflunomide 20 mg daily (n = 30) or placebo (n = 15). Active disease was defined as a score of ⩾4 on the Bath ankylosing spondylitis disease activity index (0–10), and pain of ⩾4 on a visual analogue scale (0–10). The primary efficacy variable at week 24 was the 20% response rate, as recommended by the Assessments in Ankylosing Spondylitis (ASAS) working group. Secondary outcome variables included general wellbeing, metrology index, swollen joint count, erythrocyte sedimentation rate, and C reactive protein. Results: In all, 13 women and 32 men were studied. Demographic and disease indices were comparable between the two treatment groups at baseline. The rate of ASAS 20% responders was not significantly different: 27% in the leflunomide treated patients and 20% in the placebo group (95% confidence interval, −32% to 19%). No significant differences were found between the treatment groups in mean changes of the secondary outcome variables. Eleven patients were withdrawn prematurely from the study because of adverse events (7), lack of efficacy (3), and non-compliance (1). Most frequently adverse events were gastrointestinal side effects and skin disorders. Conclusions: In this placebo controlled study, leflunomide treatment did not result in a significant improvement of the ASAS 20% response in active ankylosing spondylitis. No unexpected or severe adverse events occurred.

Prevalence of Chlamydia trachomatis in urine of male patients with ankylosing spondylitis is not increased

OBJECTIVE To compare the prevalence of Chlamydia trachomatisinfections in ankylosing spondylitis (AS) patients with controls, using DNA amplification assays in urine specimens. METHODS The prevalence of C trachomatis infections was assessed in 32 male AS patients and 120 age and sex matched controls. Urine specimens were tested by ligase chain reaction and polymerase chain reaction. In addition, blood samples of AS patients were tested on serum antibodies to C trachomatis (IgA and IgG) by a specific peptide based solid phase enzyme immunoassay. A questionnaire was used to assess the differences in sexual behaviour and ethnic origin between the two groups. AS patients were also asked about disease characteristics. RESULTS No significant differences were found between cases and controls in the prevalence ofC trachomatis infections. No associations were found between C trachomatis antibodies and disease characteristics, except for acute anterior uveitis (AAU). Four of eight (50%) AS men positive for IgG had a history of AAU in comparison with three of 24 (12.5%) IgG negative men (OR = 7.0; 95% confidence intervals: 1.1, 44.1). CONCLUSION The prevalence of Chlamydia trachomatisinfections, as detected by commercially available DNA amplification assays in urine specimens, in AS patients is not higher compared with male controls of the same age. However, there seems to be an association between specific antibodies to C trachomatis and AAU.

THU0391 Female gender is associated with a poorer response to tnf inhibitors in ankylosing spondylitis

Background Limited data are available on the influence of gender and lifestyle factors, such as smoking, alcohol consumption and Body Mass Index (BMI) on disease activity and response to TNF inhibitors (TNFi) in ankylosing spondylitis (AS). Objectives This study aimed to determine whether these factors influence age at diagnosis, disease activity and response to TNFi. Methods In a prospective study, clinical data (age, gender, C-reactive protein, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI), smoking, alcohol consumption and BMI) were collected in AS patients from a observational cohort, who started or switched treatment with TNFi. Data were collected at baseline and after 6, 12 and 24 months. Independent T-tests and linear regression analyses were performed to assess the influence of gender and lifestyle factors on age at diagnosis and disease activity. Results In total, 312 consecutive AS patients, 34% female, were included with a mean follow-up of 18.9 months. Most patients (172, 55%) showed significant improvement after start of TNFi of whom 86 patients (28%) had a clinically important (ASDAS decrease >1.1) and 86 (26.9%) a major clinical improvement (ASDAS decrease >2.2). BMI was significantly correlated with age at diagnosis (p=0.016; 95% CI: 0.07 – 0.65): an increase of BMI with three points delayed the AS diagnosis with one year. At baseline, smoking and gender were not correlated with the ASDAS, but BASDAI and BASMI were both inversely related to BMI. Male gender was significantly associated with a higher chance at clinical response (improvement of the BASDAI with 50% or a 2 point decrease) to TNFi (p=0.041). At one year follow-up the clinical improvement of males versus females was respectively 62% vs. 43% and at two year follow-up 59% vs. 46%. Males also showed a significantly higher ASDAS improvement after one year of follow-up compared to females (p=0.015). Conclusions Significantly less females had a clinical response compared to males after one and two years of TNFi treatment. A higher BMI not only prolonged the time to AS diagnosis up to one year, but also negatively influenced the BASDAI and BASMI scores. Female gender and high body weight should be taken into consideration when the efficacy of TNFi is assessed, by stratifying for these factors in the analysis. Disclosure of Interest None declared

Objective evaluation of physical functioning after tumor necrosis factor inhibitory therapy in patients with ankylosing spondylitis: a selection of 3 feasible performance-based tests.

Objective. (1) To select a limited number of performance-based tests that are reliable, show improvement in physical functioning after tumor necrosis factor inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS), and generate information equivalent to the full set of tests, and (2) are feasible for use in daily clinical practice. Methods. Eight performance-based tests were evaluated. To eliminate redundant testing, the tests that showed adequate reliability, the highest standardized response mean (SRM), and the largest proportion of patients with an improved performance-based physical functioning were selected. The selected tests were combined into a new criterion for improvement in physical functioning (AS Performance-based Improvement; ASPI). The number and percentage of improved patients identified with the ASPI and identified with the full set of performance tests were compared. Results. Reliability for all tests was adequate to excellent (ICC 0.73–0.96). The tests for bending, putting on socks, and getting up from the floor had the highest SRM (0.52–0.74) and showed the largest proportion of improved patients after TNFi therapy. The combination of these 3 tests was feasible in daily clinical practice and showed improved physical functioning after TNFi therapy in 67% of the patients. Conclusion. The 3 selected tests are recommended for use in daily practice because they generate information comparable to the full set. They are reliable and feasible, and the combination of these tests showed improved physical functioning after TNFi therapy in 67% of the patients. Evaluation of physical functioning might be improved by adding these tests to other AS outcome measures.

Comparison of drug survival and clinical outcome in patients with ankylosing spondylitis treated with etanercept or adalimumab

Objective: To compare rates of drug survival and clinical response during 2 years of follow-up in ankylosing spondylitis (AS) patients treated with etanercept or adalimumab in routine care. Method: Biological-naïve consecutive AS patients treated with etanercept (n = 163) or adalimumab (n = 82) were followed. Treatment discontinuation was due to inefficacy, adverse events, loss to follow-up, planning a pregnancy, or uveitis. Disease activity was assessed by the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP). Moderate disease activity was defined as an ASDAS-CRP < 2.1. Results: Twenty-seven patients (32.9%) treated with adalimumab and 30 (18.4%) with etanercept discontinued treatment. Cox regression analysis demonstrated a significant difference in survival rate between discontinuation of the drug in adalimumab patients compared with etanercept patients [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.3–4.5, p = 0.005; corrected for confounding factors: HR 2.5, 95% CI 1.3–4.5, p = 0.006]. There was no significant difference at 2 years of follow-up between the adalimumab- and the etanercept-treated patients in mean ± sd ASDAS-CRP (1.9 ± 1.1 and 2.0 ± 0.9, respectively, p = 0.624), and 23 out of 34 (67.6%) compared to 71 out of 117 (60.7%) reached ASDAS-CRP moderate disease activity (odds ratio 0.738, 95% CI 0.329–1.657, p = 0.530). Conclusion: No significant difference was found between AS patients treated with etanercept and those treated with adalimumab in mean ASDAS-CRP and reaching ASDAS-CRP minimal disease activity at 2 year follow-up. Drug survival rate was higher in etanercept- compared to adalimumab-treated patients. However, this should be interpreted cautiously as the risk of allocation bias cannot be excluded.