The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
WCIM 2014 SEOUL KOREA 385
Poster Session
PS 1503 Rheumatology
Drug Survival Rates of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis
Ji-Hyoun KANG1, Dong-Jin PARK1, Jeong-Won LEE1, Kyung-Eun LEE1, Lihui WEN1, Tae- Jong KIM1, Yong-Wook PARK1, Shin-Seok LEE1
Chonnam National University Hospital, Korea1
Background: We investigated the compliance of Korean patients using tumor necrosis factor (TNF) inhibitors to treat rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and identifi ed potential predictors associated with treatment discontinuation.
Methods: The study population comprised 114 RA and 310 AS patients treated with TNF inhibitors at a single tertiary center for at least 1 year from December 2002 to November 2011.
Results: Of the 114 RA patients, 64 (56.1%) discontinued their first TNF inhibitors with a mean duration of 18.1 months. By contrast, 65 of 310 patients (21.0%) with AS discontinued their fi rst TNF inhibitors, with a mean duration of 84 months. Although the survival rate did not differ among the three TNF inhibitors in the AS patients, the etanercept group had a lower discontinuation rate than the infl iximab group in the RA patients. In addition, RA patients who received corticosteroids in combination with TNF inhibitors were more likely to discontinue their TNF inhibitors. The independent predictors of drug discontinuation in AS patients were male gender and complete an- kylosis on radiographs of the sacroiliac joint.
Conclusions: Our results provide further evidence that real-life treatment outcomes of RA and AS patients may be different from those observed in randomized clinical trials.
PS 1504 Rheumatology
Leukocyte-Specifi c Protein1 Regulates T Cell Migration and Infl ammatory Arthritis
Yune-Jung Park1, Seong-Hye Hwang2, Seung-Hyun Jung3, Saseong Lee2, Susanna Choi2, Seung-Ah Yoo2, Ji-Hwan Park4, Daehee Hwang4, Seung Cheol Shim5, Chul-Soo Cho6, Yeun-Jun Chung3, Wan-Uk Kim2
The Catholic University of Korea, St. Vincent Hospital, Korea1, The Catholic University of Korea, St.
Mary’s Hospital, Korea2, Integrated Research Center for Genome Polymorphism, Department of Micro- biology, Korea3, School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Korea4, Chun- gnam National University Hospital, Korea5, The Catholic University of Korea, Yeouido St. Mary’s Hospital, Korea6
Background: Copy number variations (CNVs) have been implicated in human diseases.
However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA).
Methods: To defi ne CNVs, we used SNP genotyping data from the 500 discovery set.
The Lsp1 plasmid DNA was tagged with GFP and was then transfected into Jurkat cells. Mice genetically defi cient in Lsp1 (Lsp1 –/– mice) were induced of delayed-type hypersensitivity and antigen-induced arthritis.
Results: Here, we identifi ed a novel Lsp1 deletion variant for RA susceptibility. Differ- entially expressed genes in Lsp1-defi cient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T cell receptor activation, negatively regulates T cell migration by hampering ERK activation in vitro. In mice with T cell-dependent chronic infl ammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, RA patients show diminished expression of LSP1 in peripheral T cells with increased migratory capacity.
Conclusions: Our data highlights the importance of Lsp1 CNVs in the pathogenesis of immune diseases and provides novel insights into the mechanisms underlying T cell migration toward the infl amed synovium in RA.
PS 1505 Rheumatology
Retroperitoneal Fibrosis in- a Patient with Rheumatoid Arthritis
Yu-Jeong OH1, Won-Seok LEE2, Wan-Hee YOO2
Department of Internal Medicine, Chonbuk National University Medical School, Korea1, Division of Rheu- matology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine of Chonbuk National University Hospital-Chonbuk Nation, Korea2 Introduction: Retroperitoneal fi brosis (RPF) is a rare, chronic, and progressive disorder of unknown etiology that appears to be autoimmune in nature. RPF is characterized by chronic nonspecifi c infl ammation of the retroperitoneum leading to entrapment and obstruction of the ureters and any organs proximate to the retroperitoneum. If unrecognized early, RPF leads to ureteral obstruction and renal failure.
Case presentation: A 54-year-old man diagnosed with rheumatic arthritis (RA) at the age of 48 was treated with methotrexate and adalimumab. He presented with right lower back that had persisted for 1 month. Laboratory fi ndings showed rheumatoid factor and anti-cyclic citrullinated protein antibody levels of 53.5 IU/mL and 73.76 IU/
mL, respectively. An erythrocyte sedimentation rate of 33 mm/h and C-reactive pro- tein level of 10.25 mg/L were noted. An enhanced abdominal computed tomography scan showed abnormal tissue encasing the right common iliac artery that involved the right mid-ureter. The ureteral obstruction induced right kidney hydronephrosis. His symptoms were relieved after a right laparoscopic ureterolysis was performed, and the pathologic fi ndings revealed mild infl ammatory infi ltration into the fi brous tissue. The patient was eventually diagnosed with RPF.
Conclusion: With increasing awareness of RPF, it can be identifi ed in patients with RA to allow for early diagnosis and treatment. Therefore, clinicians should consider the possibility of RPF in patients with RA who are suffering from lower back pain, abdom- inal pain, or dysuria and order suitable imaging studies.
PS 1506 Rheumatology
Effect of Oral Prostacyclin Analogue on Serum TNF-Al- pha Level in Patients with Rheumatoid Arthritis
Hye Won Kim1, Jin Wuk Hur1 Seoul Eulji Hospital, Korea1
Background: Prostacyclin that binds to prostacyclin receptor on platelets and vascular smooth muscle cells increase intracellular c-AMP and block infl ux of calcium, resulting in antiplatelet and vasodilatory effect. As such, prostacyclin analogue is often at- tempted to patients who are accompanied by peripheral vasculopathy. TNF-alpha is a representative infl ammatory marker in rheumatoid arthritis (RA), known to be integral target to treat. Assuming that prostacyclin may show anti-infl ammatory effect, we aim to investigate serum TNF-alpha level before/after prostacyclin analogue treatment in patient with RA.
Methods: Patients with RA suffering from symptom of vasculopathy (age > 20 years, diagnosed as RA at least 3 months earlier, on stable disease modifying anti-rheumatic drug therapy) were included. Participants were given 0.02mg three times a day of beraprost sodium, an oral prostacyclin analogue. CBC, ESR, CRP, serum TNF-alpha level were measured at baseline and 4, 12 weeks after treatment. Interviews on peripheral symptoms such as tingling sense, coldness of hand and Raynaud’s phenomenon were processed at baseline and 12 weeks after treatment.
Results: Thirty-two patents were enrolled and 25 patients (male (n = 8), female (n = 17), mean disease duration 3.7 years) completed the study for 12 weeks. Most patients were on 3 or more DMARDs. Patients with ESR = 40mm/hr or with CRP = 2.0 mg/dL showed a declining tendency of serum TNF–alpha level at 4 weeks and at 12 weeks after prostacyclin analogue treatment, though it did not reached statistical signifi - cance (p=0.367, p=0.227) probably due to lack of numbers of participants.
Conclusions: TNF-alpha is an integral pro-infl ammatory cytokine, against which tar- geted treatment for RA are fl ourishing. We showed serum TNF-alpha level before and after treatment of prostacyclin analogue. Our results suggest anti-infl ammatory effect of prostacyclin that may have a role in treatment of RA.
The Korean Association of Internal Medicine
386 32nd World Congress of Internal Medicine (October 24-28, 2014)
PS 1507 Rheumatology
Effect of Anti-Tumor Necrosis Factor Alpha Treatment of Rheumatoid Arthritis and Chronic Kidney Disease
Young Hyup Lim1, Hyun Woo Kim1, Eun-Jung Park1, Chang-Keun Lee2, Jung-Yoon Choe3, Hoon-Suk Cha4, Jinseok Kim1
Department of Medicine, Jeju National University Hospital, Jeju University School of Medicine, Korea1, Department of Medicine, University of Ulsan College of Medicine, Asan Medical Center, Korea2, Depart- ment of Medicine, Catholic University of Daegu, School of Medicine, Korea3, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Korea4
Background: Rheumatoid arthritis (RA) and chronic kidney disease (CKD) are very prevalent and so often coincide. Among various anti-inflammatory agents, TNF-a blocking drugs reportedly stabilize renal function in RA patients with CKD and/or sec- ondary renal amyloidosis by suppressing infl ammation. However, there are no available data supporting the effi cacy of anti-TNF-a agents in a larger population of RA patients with renal insuffi ciency. The aim of study was to investigate the impact of anti-tumor necrosis factor alpha (TNF-a) therapy on progression of CKD in patients with RA.
Methods: Seventy patients with RA and CKD were retrospectively analyzed. Outcomes were evaluated using the difference in the annual change of estimated glomerular fi ltration rate (eGFR) between patients with treated with anti-TNF-a or without.
Results: There was a tendency toward stabilization of eGFR after a median of 2.6 years (interquartile range, 1.2-4.2 years) from 50.3 ± 8.4 ml/min/1.73 m2 to 54.5 ± 16.0 ml/min/1.73 m2 in patients received anti-TNF-a therapy (p=0.084). Conversely, eGFR decreased signifi cantly in patients not receiving anti-TNF-a therapy after a me- dian of 3.0 years (interquartile range, 1.8-4.6 years) from 50.9 ± 7.7 ml/min/1.73 m2 to 43.7±10.9 ml/min/1.73 m2 (p<0.001). The annual change of eGFR was signifi cantly different between patients treated with anti-TNF- drugs and without (2.0 ± 7.0 ml/
min/1.73 m2/y versus -2.9 ± 5.8 ml/min/1.73 m2/y; difference in mean values, -4.9 ml/
min/1.73 m2/y; 95% confi dence interval, -7.5 to -2.2; p=0.002). Use of anti-TNF-
drugs was also signifi cantly associated with positive annual change of eGFR in logistic regression analysis (p=0.009).
Conclusions: Among patients with RA and CKD, treatment with anti-TNF-a drugs was associated with less renal function decline. Anti-TNF-a drugs may be benefi cial for managing RA combined with CKD.
PS 1508 Rheumatology
Diffusing Weight Magnetic Resonance Imaging May Suggest the Treatment Strategy in Ankylosing Spondy- litis
Sang Yeob Lee1, Sung Won Lee1, Won Tae Chung1 Dong-A University Medical Center, Korea1
Background: This study aimed to determine the value of diffusion-weighted MR im- aging (DWI) in determined of ankylosing spondylitis (AS) treatment strategy and assess the role of quantitative MRI in the evaluation of AS treatment outcome.
Methods: 18 patients with the diagnosis of early AS were included in this study. Disease activity was measured according to clinical instruments and laboratory tests. For each patient, both infl amed sacroiliac (S-I) joint lesion was checked quantitatively at fi rst diag- nosis by diffusion-weighted imaging (DWI) measuring the apparent diffusion coeffi cient (ADC) and by dynamic contrast-enhanced imaging (DCEI) with evaluation of the enhance- ment factor (fenh) and enhancement gradient (genh). All patients were revaluated by pelvis computer tomography (CT) for bone change in S-I joint, after two year.
Results: Clinical and quantitative MRI parameters diminished signifi cantly with regres- sion of the infl ammatory activity. Median ADC values in AS patients were (1.118 ± 0.122)
× 10-3 mm2/s in S-I joint. The high ADC (>1.118 ± 0.122) × 10-3 mm2/s, fenh (>1.65) and genh (2.09 %/S) were associated severe disease activity and early administration of biologics (p<0.05). In each individual, the high ADC, fenh and genh of S-I joint lesion was associated more severe localized pain than the other S-I joint, despite treatment (p<0.05).
Paradoxically, early administration of biologics group who was high disease activity at the diagnosis had minimal bone change of S-I joint, compared to only NSAIDs used group who was low disease activity in pelvis CT fi nding two year later.
Conclusions: Diffusion-weighted imaging and DCEI were shown to be effective in quantifying changes in infl ammation in S-I joint at the diagnosis of AS, and could be convenient for assessing treatment strategy.
PS 1509 Rheumatology
Il-6 Maybe a Crucial Role in Peripheral Arthritis of Non-Radiographic Axial Ankylosing Spondylitis by Toll- Like Receptor 2 and 4
Sang Yeob Lee1, Sung Won Lee1, Won Tae Chung1 Dong-A University Medical Center, Korea1
Background: The blocking of IL-6 therapy is not effective treatment of AS in recent report, but the role of blocking IL-6 on peripheral joint in non-radiographic axial AS is unknown. So we studied the blocking of IL-6 in peripheral arthritis of non-radiograph- ic axial AS.
Methods: Synovial fi broblast (FLS) were obtained from knee of eight non-radiograph- ic axial AS patients who were high BASDAI score (>6), and six RA patients who were moderate DAS28 score (>3.2). The expression of IL-6 was analyzed by real-time pol- ymerase chain reaction and multiplex secretary protein analysis technology, Bio-plex assay, also the expression of toll like receptor (TLR) in FLS was detected by western blot.
Results: The expression of TLR 2 and TLR 4 were observed on AS and RA FLS. The ad- ministration of peptidoglycan for TLR 2 and LPS for TLR 4 increased the level of IL-6 in AS and RA FLS. The treatment of AS FLS with IL-6 inhibitor, tocilizumab, resulted in reduced expression of TLR 2 and TLR 4 in AS FLS and re-administration of peptido- glycan for TLR 2 and LPS for TLR 4 treatment did not increased the expression of IL-6, TLR 2 and TLR 4 in AS FLS.
Conclusions: Our results suggest that IL-6 maybe crucial role in peripheral arthritis of non-radiographic axial AS and blocking of IL-6 may ameliorate peripheral arthritis of AS by regulating TLR 2 and TLR 4, so inhibition of IL-6 maybe a potential therapeutic strategy in peripheral arthritis of non-radiographic axial AS.
