Sung Hae Chang

Clinical factors and treatment outcomes associated with failure in the detection of urate crystal in patients with acute gouty arthritis.

Background/Aims To investigate the rate of detection of monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with acute gouty arthritis and factors associated with false-negative results. Methods A total of 179 patients with acute gouty arthritis who had undergone SF crystal examination were identified from the data warehouse of two university hospitals. Clinical and laboratory data were obtained from the medical records. Results The overall rate of detection of MSU crystals was 78.8%. In univariate analyses, the only significant differences between the variables of crystal-negative and crystal-positive patients were a lower C-reactive protein level (p = 0.040) and fewer patients undergoing emergent surgery in the crystal-positive group (p = 4.5 × 10-6). In logistic regression analyses, MSU crystal-negative results were significantly associated with the interval from arthritis onset to crystal examination (p = 0.042), and this was the most significant risk factor for arthroscopic surgery (p = 2.1 × 10-4). Seventeen patients who underwent arthroscopic surgery had a significantly longer hospital stay (p = 0.007) and a significant delay in gout treatment (p = 8.74 × 10-5). The distribution of crystal-negative patients differed significantly between the SF samples that were evaluated by both the laboratory medicine and the rheumatology departments (p = 1.2 × 10-14), and the κ value was 0.108. Conclusions Although several clinical features were associated with detection failure, SF MSU crystal identification was critically dependent on the observer. Considering the impact on the treatment outcomes, implementation of a quality control program is essential.

Chronic Periodontitis Is Associated With Spinal Dysmobility in Patients With Ankylosing Spondylitis

BACKGROUND Although microbes have been suggested to play a role in the pathogenesis of ankylosing spondylitis (AS), several studies present contradictory results regarding the association between AS and chronic periodontitis (CP). METHODS Clinical, laboratory, and medication data were collected from 84 patients with AS and 84 age- and sex-matched controls. Periodontal measurements, including probing depths (PDs), clinical attachment loss (AL), serum anti-Porphyromonas gingivalis titers, and the detection of P. gingivalis DNA in gingival crevicular fluid, were recorded. All participants with periodontitis with PD ≥4 to <7 mm received scaling and root planing and were re-evaluated at 12 weeks; those still exhibiting periodontitis with PD of ≥4 to <7 mm at 12 weeks were followed at 24 weeks. RESULTS The prevalence of moderate-to-severe CP was not different between patients with AS and controls (70.2% versus 66.6%). The P. gingivalis detection rate was not different between patients with AS and controls or between patients with AS receiving and not receiving anti-tumor necrosis factor (TNF)-α agents. However, CP was positively associated with impaired spinal mobility of patients with AS in multivariate analyses. After periodontal treatment, PD and AL levels were improved in both groups, but the change was significantly greater in patients with AS than in controls. Patients with AS receiving anti-TNF-α agents exhibited a greater improvement in PD and AL than those who did not. CONCLUSIONS Although AS was not associated with the presence of CP, CP was associated positively with the severity of spinal dysmobility in Korean patients with AS. These results suggest that periodontitis can have a negative effect on axial movement in AS.

Clinical and Laboratory Characteristics and Mortality in Korean Patients with Systemic Sclerosis: A Nationwide Multicenter Retrospective Cohort Study

Objective. We aimed to investigate demographic and clinical features and predictors of mortality in Korean patients with systemic sclerosis (SSc). Methods. We performed a retrospective multicenter medical chart review in Korean patients diagnosed with SSc from 1986 to 2016 at 11 university hospitals representing each geographic area of Korea. SSc patients were defined according to the American College of Rheumatology preliminary classification criteria and subtyped as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc. Results. We enrolled 751 patients (female, 86.7%; mean age at diagnosis, 48.9 yrs). The most common organ involvement was interstitial lung disease (52.7%), followed by gastroesophageal reflux disease (32.9%) and pulmonary arterial hypertension (13.6%). Patients with lcSSc were more common than those with dcSSc (64.8 vs 35.2%), whereas anti-Scl-70 and anticentromere antibody positivity were identified in 302 (42.5%) and 175 (25.5%) patients, respectively. In the 46 (6.1%) patients who developed a malignancy, lung cancer (23.9%) was the most common diagnosis, followed by gastric (13%) and breast cancer (13%). During the study period, 57 (7.6%) patients died, and the 5- and 10-year survival rates were 94% and 87%, respectively. Increased age at diagnosis, cardiovascular involvement, and anti-Scl-70 antibody positivity were significant predictors of death. Conclusion. Clinical manifestations and survival rates in Korean SSc patients are similar to those of other populations. However, the prevalence of anti-Scl-70 antibody is higher in Korean SSc patients compared with whites, while the prevalence of anticentromere antibody is lower.

A Case of Primary Sjögren’s Syndrome Presenting as Mass-Like Encephalitis, With Progression to Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica is an idiopathic inflammatory demyelinating disease of the central nervous system (CNS) that predominantly affects the optic nerves and spinal cord. With the discovery of the pathogenic anti-aquaporin-4 (AQP4) antibody, the disease was recognized as part of a spectrum of autoimmune diseases that target AQP4, collectively referred to as neuromyelitis optica spectrum disorder (NMOSD). NMOSD consists of conditions that affect various parts of the CNS with the AQP4 antibody. In this article, we report a 43-year-old female patient who was initially diagnosed with primary Sjögrens syndrome (pSS) with CNS involvement, but was later diagnosed with overlapping pSS and NMOSD, which required more intensive treatment. The patient presented with fever, headache, dysarthria, and left-side weakness, and brain imaging showed a mass-like edematous lesion in the right frontoparietal region. She also complained of xerostomia and was diagnosed with pSS by salivary scintigraphy, anti-Sjögrens syndrome A positivity, and minor salivary gland biopsy. Under the diagnosis of pSS with CNS involvement in the form of tumefactive encephalitis, she was treated with high-dose steroids and monthly intravenous cyclophosphamide therapy. However, three months later, she developed a sudden decrease in right visual acuity and had right optic neuritis. Her serum was positive for the anti-AQP4 antibody, and she was finally diagnosed with overlapping NMOSD and pSS. She was treated with steroid pulse therapy and plasmapheresis. Therefore, in patients with pSS presenting with cerebral white matter lesions, even when optic neuritis or myelitis is absent, evaluations for the anti-AQP4 antibody should be considered to detect and treat NMOSD accordingly.

AB0392 Safety and effectiveness of CT-P13 in patients with rheumatoid arthritis: results from 24 months nationwide registry in korea

Background CT-P13 is approved in both European Union and United States, and licensed for use in 79 countries around the world as a biosimilar to innovator infliximab (INX). The independent registries of CT-P13 have been conducted in a number of European countries and Korea [1]. Objectives To evaluate safety and effectiveness of CT-P13 when administered in a real-life setting in active RA patients. Methods This study collected data of patients who were treated with CT-P13 from 2013 December to 2016 June. Efficacy was assessed at baseline and every 6 months thereafter using DAS28 (ESR) and/or DAS28 (CRP) and collection of adverse events (AEs) was performed. Immunogenicity was assessed at baseline, Week 30 and every year during CT-P13 treatment period. Results Total 125 patients were enrolled; 104 patients started treatment with CT-P13 (Naïve group) and 21 patients (8 from INX, 13 from other anti-TNFs) switched treatment to CT-P13 (Switching group). The mean (SD) duration since RA diagnosis was 6.5 (±6.85) years for all patients. Of all patients treated with CT-P13, only 4.8% (6/125) of patients changed to other anti-TNFs. Two of six patients changed treatment within 8 month after starting CT-P13. The proportion of patients achieving clinical remission by DAS28 (ESR/CRP) increased gradually (Figure 1). DAS28 (ESR/CRP) value decreased from baseline at 6 months and it maintained thereafter (Table 1). Switching group also showed similar results that remission rate by DAS28 (CRP) was 42.9% (3/7) and mean actual value was 2.85 at 12 months. For Naïve group, 50% (52/104) of patients had at least one positive anti-drug antibody result and it is consistent to other published study [2]. Overall safety summarized as the percentage of patients with at least one treatment emergent AE (TEAE) was similar or lower after switching to CT-P13 (Table 2). No cases of active tuberculosis were reported.Table 1. DAS28 in CT-P13 Naïve group over 24 months Baseline 6 months 12 months 18 months 24 months DAS28 (ESR) n 67 62 40 14 3 Mean 5.78 3.61 3.30 3.01 2.42 SD 1.14 1.40 1.22 1.03 0.74 DAS28 (CRP) n 63 61 39 14 3 Mean 5.06 2.97 2.59 2.35 1.81 SD 1.19 1.21 1.06 0.69 0.63Table 2. Safety results in CT-P13 Naïve and Switching group Naïve group Switching group TEAEs 80.8% (84/104) 66.7% (14/21) Related TEAEs 31.7% (33/104) 28.6% (6/21) Infection and Infestation 42.3% (44/104) 33.3% (7/21) Conclusions The overall safety profile revealed that CT-P13 is well-tolerated in patients with RA and remission rate for 24 months also showed that CT-P13 is efficacious under real world practice. References Glintborg et al. ACR 2016. Krintel et al. Rheumatology 2013. Disclosure of Interest None declared

THU0211 Low Dose Etanercept Treatment for Maintenance of Clinical Remission in Ankylosing Spondylitis: Retrospective Cohort Study

Background Dose reduction of etanercept after clinical remission in patients with ankylosing spondylitis (AS) is not uncommon practice. However, efficacy and optimal schedule of dose tapering is rarely evaluated. Objectives To investigate the efficacy and safety of low dose etanercept treatment (25mg or less/week) after clinical remission of AS in real world. Methods In this study, 134 AS patients who treated with etanercept for at least 12 months and achieved clinical remission (BASDAI <4 and normal C-reactive protein level) between 2004 and 2013 were enrolled. Dose reduction was performed in 100 patients (low dose group) after achieving clinical remission based on physicians medical decision. Other 34 patients (standard dose group) maintained the dosage of 50mg/week until discontinuation. Drug survival (time to drug discontinuation due to inefficacy or adverse event) and incidence of significant adverse events were compared between two groups. In patients with low dose group, clinical factors and time to dose reduction associated with longer drug survival were estimated. Results Clinical and demographic features were comparable between two groups at the time of starting etanercept except for age (43.4 years in low dose group vs. 52.0 years in standard dose group, p=0.001). In low dose group, median time to dose reduction was 19.5 (10.1-39.6) weeks. During 536.8 person-years (PYs) of follow up, 27 patients stopped etanercept (21/440.9PYs in low dose group and 6/95.9PYs in standard dose group). Crude drug survival of low dose group was not significantly different from that of standard group (98.0% vs. 93.5% at 2 years, 92.1% vs. 89.4% at 3 years and 84.4% vs. 76.2% at 4 years). This finding was consistent after adjustment of clinical factors including age, gender, disease duration, initial BASDAI, concomitant MTX and previous TNF-blocker use (adjusted HR=0.552, 95% C.I. 0.208-1.465) (Figure). Incidence of adverse events which led to discontinuation of etanercept also showed no difference between two groups (40.82/1000PYs in low dose group vs. 52.16/1000PYs in standard dose group, p=0.783). In the subgroup analysis with low dose group, dose reduction after more than 24 weeks of standard dose treatment was significantly associated with longer drug survival after adjustment of other clinical factors (adjusted HR 0.273, 95% C.I. 0.085-0.875). Conclusions In patients with AS who achieved clinical remission, low dose etanercept treatment showed comparable long-term efficacy and safety in real world. Among various strategies of dose reduction, more than 24 weeks of standard dose treatment before adjustment was associated with longer drug survival. Disclosure of Interest None declared

FRI0015 The effect of cxcl10 blockade in c protein-induced myositis

Background CXCL10 (also called interferon-γ-inducible protein 10 [IP-10]) is a chemokine that plays a critical role in the infiltration of T cell in autoimmune disease such as RA and SLE. CXCL10 is reported to be expressed in muscle tissue of polymyositis. Objectives We investigated the role of CXCL10 and the effect of CXCL10 blockade in C protein-induced myositis, an animal model of polymyositis. Methods C protein-induced myositis model was induced with human skeletal C protein fragment in 8-week-old female C57BL/6 mice. Immunohistochemistry was performed to detect CXCL10 and CXCR3, its receptor in muscle tissue. CXCR3 in mouse splenocyte was investigated by flow cytometry. Migration assay of mouse splenocyte was performed with 5 μm pore transwell system. Mice with C protein-induced myositis were treated with anti-CXCL10 antibody or control IgG 8 days after the induction of myositis and the inflammation in muscle tissue was assessed 3 week after the induction. Results Immunohistochemistry showed the expression of CXCL10 and CXCR3 in the muscle of C protein-induced myositis. Flow cytometry demonstrated increased CXCR3+CD4+ T cells (normal mice, 14.14%±1.09% vs. C protein-induced myositis, 37.50%±5.63%) and CXCR3+CD8+ T cells (normal mice, 35.55±2.41% vs. C protein-induced myositis, 79.00%±0.89%) in C protein-induced myositis. Moreover, it was showed that IFN-γ+ cells were increased among CXCR3+CD8+ T cells compared to CXCR3-CD8+ T cells (CXCR3+CD8+ T cell, 28.0 ± 4.2% vs. CXCR3-CD8+ T cell, 9.5 ± 1.5%, p = 0.016). Migration of splenocyte was increased in response to CXCL10 (chemotactic index=1.91±0.45). Treatment with anti-CXCL10 antibody (n=10) showed less inflammation score in muscles than treatment with control IgG (n=10; median [range], anti IP-10, 0.75 [0.25-2.00] vs. control IgG, 1.43 [1.125-4.25], p=0.045). Conclusions CXCL10 was expressed in the inflammation of C protein-induced myositis model and its blockade suppressed inflammation in muscle. Disclosure of Interest None Declared