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Background Calprotectin (S100A8/9) is a damage-associated molecular pattern molecule that is involved in the early phase of tissue injury. It is found mainly in circulating neutrophils, monocytes and macrophages of rheumatoid arthritis (RA) synovial tissue where it acts as a chemoattractant and induces production of proinflammatory cytokines. Several studies have reported its association with clinical disease activity and radiographic damage in patients with RA. Objectives The aim of our study was to analyse the plasma levels of calprotectin in patients with established RA after the abatacept treatment compared with healthy individuals, and to examine their potential association with disease activity and treatment response. Methods The plasma levels of calprotectin were determined by ELISA (BUHLMANN Laboratories AG) in 40 patients with established RA before and 3 months after initiation of abatacept treatment, and in 30 age–/sex-matched healthy subjects. Disease activity was evaluated by 28-joint Disease Activity Score (DAS28). The CRP levels and erythrocyte sedimentation rate (ESR) were determined by routine laboratory techniques. Data are presented as median ±IQR. Results Calprotectin levels at baseline were significantly higher in patients with established RA than in healthy individuals (1925 [741; 4093] vs. 506 [302; 754] p Conclusions We demonstrate here decrease in plasma levels of calprotectin after 3 months of abatacept therapy in patients with established RA, its association with disease activity and disease activity improvement over time. Acknowledgements Supported by the project of MHCR for conceptual development of research organisation 00023728, research project SVV 260 373. Disclosure of Interest None declared

Objective To compare the effectiveness, safety and costs of standard versus individually tailored reduced doses of anti-tumour necrosis factor (TNF) drugs in patients with ankylosing spondylitis (AS) after achieving low-disease activity. Methods This was a single-centre prospective observational study performed within the ATTRA registry. The anti-TNF dose tapering strategy was chosen by treating physicians, without prespecified protocol. We used propensity score (PS) methodology to identify two cohorts of patients matched for relevant baseline characteristics who were treated with either reduced (n=53) or standard (n=83) doses of TNF inhibitors. One-year outcomes and costs of anti-TNF drugs were compared between both PS-matched cohorts. Results In the reduced dosing group, the median dose of TNF inhibitor corresponded to 0.67 and 0.5 of the standard dose initially and at 12 months respectively, and 21% of patients required return to standard dosing regimen. The mean change per year in Bath Ankylosing Spondylitis Activity Index, C-reactive protein , Health Assessment Questionnaire Disability Index and Bath AS functional index, as well as quality-adjusted life-year area under the curve were no different between both groups. The HR (95% CI) of reduced versus standard dosing group for relapse and any adverse event was 1.46 (0.66 to 3.19) and 0.56 (0.22 to 1.44), respectively. Mean difference (95% CI) in cost of anti-TNF drugs was €−4214 (−4707 to −3701) per year of treatment in favour of reduced dosing strategy. Conclusions In patients with AS after reaching low-disease activity, a tailored approach to reduce doses of anti-TNF drugs produced similar clinical outcomes at 1 year, but was substantially less costly.

Objective An increased incidence of allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) in several inflammatory diseases has recently been reported. The aim of this study was to examine a variable number tandem repeat (VNTR) polymorphism of the IL1RN gene in patients with juvenile idiopathic arthritis (JIA). Methods Findings in 185 Czech patients with JIA were compared with those in 168 Czech controls, 50 JIA patients and 52 controls of Turkish origin, and 79 controls from central England. VNTR polymorphism analysis of IL1RN was performed by polymerase chain reaction using 2 flanking primers to amplify an 86-bp tandem repeat region in intron 2. Results The frequency and carriage rate of IL1RN*2 were significantly increased in Czech JIA patients compared with the Czech controls (frequency 27.6% versus 15.8%; carriage rate 44.3% versus 26.2%). Increased frequency and carriage rate of IL1RN*2 were found in 23.3% and 40.0% of Turkish JIA patients and in 17.3% and 34.6% of ethnically matched controls. The high representation of IL1RN*2 in 52.3% of the 22 patients with extended oligoarthritis, 31.3% of the 56 patients with enthesitis-related arthritis, and 42.9% of the 14 patients with other arthritis was particularly responsible for the increased frequency of IL1RN*2 in the Czech JIA patients. We found no association of IL1RN*2 with disease activity or severity parameters. Conclusion Inheritance of IL1RN*2 may contribute to genetic susceptibility in several forms of autoimmune diseases, including JIA. The IL1RN*2 allele may be useful as a prognostic indicator of the evolution of an extended oligoarticular course of JIA.

Objectives To analyze the efficacy and safety of biologic agent in adult patients with juvenile idiopathic arthritis (JIA). Methods ATTRA is a Czech national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analysed adult JIA patients, who switched from TNF antagonists to another biologic treatment. Patients were treated in recommended doses for RA and the first drug was either infliximab (56.5%), or etanercept (23.6%), or adalimumab (19.9%). Those patients, who failed to improve in DAS28 by at least 1.2 after 3 months at 2 consecutive visits, who lost the response during the treatment, or who had to be discontinued due to adverse event, were switched to alternative anti-TNF or other biologic drug. Survival on therapy after 1st and 2nd biologic agents was calculated. Clinical efficacy was assessed with DAS28. Safety assessments were done for all patients during the whole follow-up period. No guidelines have been issued for preference of the 1 st or 2 nd drug type and this was left purely to treating physician decision and was based on the assessment of overall clinical situation. Results One hundred and sixty one adult JIA patients were treated with anti-TNF agents. Mean age of patients was 24.3 years, duration of disease was 14.3 years and 64% were women. Seventy seven (47.8%) patients received more than one biologic agent. DAS28 showed excellent and persistent improvement for those patients, who remained on the first drug. Response to second biologic agents was also significant, although with smaller differences to baseline DAS28. DAS28 at week 0 was 5.94±1.39 and decreased significantly to 2.77±1.44 at week 54 and 2.24±1.52 at week 108: Response to second anti-TNF was also significant, although with smaller differences to baseline DAS28; weeks 0, 54 and 108 were 5.84±1.36, 2.92±1.38, and 2.83±1.07, respectively. Survival on the treatment was not statistically different in the first users in comparison with switched patients (p = 0.656); somewhat lower adherence to therapy was seen with the second agent (in first users and in switched patients, respectively: 1st year - 0.91 (95% CI: 0.86-0.95) and 0.88 (95% CI: 0.78-0.93); second year - 0.84 (95% CI: 0.77-0.89) and 0.71 (95% CI: 0.58-0.81). Adverse events that lead to treatment discontinuation were observed during 1st and 2nd year of treatment with the first biologic drug in 6% and 8% and in 7% and 13% with the second agent. Treatment discontinuation due to inefficacy was observed with the 1st drug in 2% and 5 %, and in 3% and 9% with the 2 nd agent during treatment years 1 and 2. Conclusions biologic treatment in adult patients with juvenile idiopathic is effective and safe. Similarly to patients with RA, it is possible to regain efficacy after switching to second biologic drug in a majority of patients, although with somewhat lower difference between entry and 2 years DA28 evaluation. Good adherence to therapy was observed for both first and second biologic agents. Acknowledgements Supported by Research Project from Ministry of Health in the Czech Republic No: 000 000 23728 Disclosure of Interest None Declared