Y.S. Suh

Drug survival and the associated predictors in South Korean patients with rheumatoid arthritisreceiving tacrolimus

Background/Aims To investigate the drug survival rate of tacrolimus (TAC) and analyze the potential predictors of this rate in patients with rheumatoid arthritis (RA) in routine care. Methods2018-01-16 In this retrospective longitudinal study, we enrolled 102 RA patients treated with TAC from April 2009 to January 2014 at a tertiary center in South Korea. The causes of TAC discontinuation were classified as lack of efficacy (LOE), adverse events (AEs), and others. The drug survival rate was estimated using the Kaplan-Meier method and the predictors of this rate were identified by Cox-regression analyses. Results TAC was discontinued in 27 of 102 RA patients (26.5%). The overall 1-, 2-, 3-, and 4-year TAC continuation rates were 81.8%, 78.4%, 74.2%, and 69.1%, respectively and the median follow-up period from the start of TAC was 32.5 months. The number of TAC discontinuations due to LOE, AEs, and others were 15 (55.6%), 11 (40.7 %), and 1 (3.7%), respectively. The baseline high disease activity was a significant risk factor for TAC discontinuation after adjusting for confounding factors (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.16 to 5.35; p = 0.019). In addition, underlying interstitial lung disease was significantly associated with TAC withdrawal due to AEs (HR, 3.49; 95% CI, 1.06 to 11.46; p = 0.039). Conclusions In our study, TAC showed a good overall survival rate in patients with RA in real clinical practice. This suggests that the long-term TAC therapy has a favorable efficacy and safety profile for treating RA.

Development of autoimmune hepatitis in a psoriasis patient without immunosuppressive therapy

We present a case of a 65-year-old man with psoriasis who developed autoimmune hepatitis (AIH) without receiving immunosuppressive therapy with either anti-tumor necrosis factor-α or methotrexate. The AIH had completely resolved at 2 months after prednisolone and azathioprine therapy. This case confirms the need to consider AIH in psoriasis patients who experience new elevations in liver enzymes. To our knowledge, this is first description of the development of AIH in an immunosuppressant-naïve patient with psoriasis.

AB0155 Periostin Deficiency Aggravates Inflammation and Joint Destruction in an Animal Model of Rheumatoid Arthritis

Background Periostin is a matricellular protein that expressed in bone, periodontal ligament, heart valve, tendon and skin. Previous study indicated that periostinis linked with several inflammatory diseases such as airway hypersensitivity, periodontal inflammation, and pulmonary fibrosis. However, there is no study to investigate the role of periostin in rheumatoid arthritis (RA). Objectives This study was performed to assess the function of periostin in K/BxN serum transfer arthritic mice. Methods Synovial tissues, serum, joint fluid, and fibroblast-like synoviocyte (FLS) were obtained from patients with RA and osteoarthritis (OA). The expression of periostin in synovial tissues was assessed by immunohistochemistry. The levels of periostin were checked by Western blot and enzyme-linked immunosorbent assay (ELISA). K/BxN serum transfer arthritis was induced in periostin knockout (KO) and age-matched wild type (WT) mice. Arthritis severity was assessed by clinical and histopathologic scoring. The levels of inflammatory cytokines in ankles and serum were measured by quantitative PCR and ELISA. The osteoclastogenesis was assessed by using bone marrow monocytes (BMM) from periostin KO or WT mice. Results Periostin was highly expressed in the synovium of RA patient than OA. The periostin levels were increased in the presence of IL-1β and TNF-α in RA-FLS. The periostin KO mice showed more severe arthritis from day 4 to day 10. The peak clinical scores were: 5.0±0.6 in WT, 7.36±0.5 in periostin KO mice; p<0.01). The periostin KO mice showed aggravated histopathologic findings than WT, respectively: synovial inflammation (3.5±0.6 vs 2.2±0.4; p<0.05), bone erosion (3.8±0.6 vs 1.9±0.5; p<0.05) and cartilage damage (3.2±0.7 vs 1.8±0.5; p<0.05). The level of IL-1b was increased in the serum of periostin KO mice than WT (18 pg/ml ±7.0 vs 5 pg/ml ±1.2; p<0.01). BMMs from periostin KO mice had more TRAP-positive multinucleated cells than WT. Conclusions This study suggests that regulation of periostin contributes to pathogenesis of RA and periostin has a potential protective role in RA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4201

AB0140 The role of raf kinase inhibitory protein in rheumatoid arthritis

Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of the joints and is characterised by immune cell infiltration, synovial hyperplasia, and destruction of cartilage and underlying bone 1. Raf kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, has been implicated as a suppressor of metastasis and NF-κB pathway in cancers 2. Objectives The NF-κB and ERK pathways are considered to be one of the most important pro-inflammatory signalling pathways in RA. Therefore, RKIP might be a potential therapeutic target for RA. However, whether and how RKIP regulates RA is not fully understood. The present study was performed to examine whether and how RKIP are differentially regulated in RA. Methods The expressions of RKIP were assessed in synovial tissue, fluid and fibroblast-like synoviocytes (FLS) from patients with RA and osteoarthritis (OA) by immunofluorescence staining and western blotting. RA- or OA-FLS were infected with either a recombinant adenoviral RKIP overexpressing vector (Ad-RKIP) or shRNA-expressing vector (Ad-shRKIP). Control cells infected with a GFP-targeted recombinant adenoviral vector (Ad-shGFP) (figure 1C). And then, we investigated the effects of RKIP on the migratory activity and invasion rates of FLS by transwell migration and invasion assay. Results Here, we show that RKIP expression is inversely correlated with RA. The levels of RKIP were significantly decreased in fibroblast-like synoviocytes (FLS), synovial fluid and synovium of RA patients compare to OA patients. And also find that migration and invasion of RA-FLS were significantly increased by the inhibition of RKIP compare to OA-FLS. Knockdown of RKIP in RA or OA-FLS resulted in a dramatic increase of MMP3 and IL6. We also found osteoclastogenesis of RAW cells were increased by the knockdown of RKIP. Conclusions Our data identify a role of RKIP in RA and suggest that further studies on the potential involvement of RKIP will be beneficial in better understanding the pathology of and providing a new target for treatment for RA. References [1] Ospelt C. Synovial fibroblasts in 2017. RMD Open2017;3(2):e000471. [2] Yesilkanal AE, Rosner MR. Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of signaling networks in cancer. Crit Rev Oncog. 2014;19:447–454. [3] Noh HS, Hah YS, Ha JH, Kang MY, Zada S, Rha SY, Kang SS, Kim HJ, Park J, Byun J, Hahm JR, Shin JK, Jeong S, Lee Y, Kim DR. Regulation of the epithelial to mesenchymal transition and metastasis by Raf kinase inhibitory protein-dependent Notch1 activity. Oncotarget2016;7(4):4632–46. Disclosure of Interest None declared

SAT0450 Impact of Myofascial Pain Syndrome on Pain and Functional Status in Patients with Hand Osteoarthritis

Background Various upper extremity musculoskeletal diseases (MSDs) can affect pain and disability in patients with hand osteoarthritis (HOA). However, there was no previous study investigating the relationship between upper extremity MSDs and HOA. Objectives To explore the influence of major upper extremity MSDs on pain severity and functional status of patients with HOA. Methods In this study, we enrolled 1150 farmers who lived in Gyeongnam province in Korea from June 2013 to December 2015. Physical examinations were performed by rheumatologists, orthopedists, and rehabilitation specialists. Grip powers of both hands also were evaluated. Plain radiography, a nerve conduction velocity (NCV) examination, and magnetic resonance imaging (MRI) of shoulders were performed. The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) was used to assess pain severity and functional status of hand joints. The diagnosis of HOA was made by the 1990 American College of Rheumatology classification criteria. Carpal tunnel syndrome (CTS) was confirmed by NCV findings, and rotator cuff tear (RCT) was diagnosed by MRI findings. Myofascial pain syndrome (MPS) was diagnosed by palpations of myofascial trigger points. Results Of 1150 participants, 307 were diagnosed with HOA. Among HOA patients, 151 (49.7%), 192 (62.5%), and 249 (80.1%) patients had CTS, RCTs, and MPS, respectively. HOA patients with MPS showed significantly higher AUSCAN scores (350.4±285.0 vs 200.4±201.8, p<0.001) and decreased grip power of a dominant hand (22.5±9.8 vs. 26.2±9.8, p=0.011) compared with HOA without MPS. Linear regression analysis also showed that MPS was associated with AUSCAN scores after adjustment for age and gender (β=0.21, p=0.001). The existence of CTS or RCT did not influence on AUSCAN scores and grip power. Compared to participants with none of major upper extremity MSDs, participants with MPS only were also higher AUSCAN scores. Conclusions MPS has a significant impact on pain and functional status in patients with HOA. Therefore, management of coexisting MPS is the better way to improve pain and function of hand joints in patients with HOA. Acknowledgement This study was supported by a grant of the Center for Farmers Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. Disclosure of Interest None declared

AB1191 High Prevalence of Various Upper Limb Musculoskeletal Disorders in Korean Orchardists

Background Orchardists are expected to show high prevalence of upper limb musculoskeletal disorders (MSDs) due to their heavy works and working postures. However, there are no systematic studies relating upper limb MSDs in Korean orchardists. Objectives To evaluate the prevalence and characteristics of upper limb MSDs among orchardists in rural areas of Korea. Methods The study was carried out from June 2013 to May 2014 in a tertiary medical center. The physical examinations of upper extremities were performed by rheumatologists, orthopedists, and rehabilitation medicine specialists. The plain radiographs of shoulder, elbow, and hand, nerve conduction examination of upper extremities, and MRI of both shoulder were taken. The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was used to assess symptoms and function of upper extremities. Results Five hundred and fifty orchardists were included. Participants comprised of 49.5% female and 50.5% male with mean age of 59.5±8.1 years. The mean farming duration was 31.3±13.2 years. A total of 34 different types of upper limb MSDs were detected. The most frequent disorder was myofascial pain syndrome (80.5%) followed by rotator cuff syndrome (58.9%), hand osteoarthritis (58.0%), carpal tunnel syndrome (42.9%), and lateral epicondylitis (39.5%). Prevalence of any form of MSD was 98.5% and of three and more of MSDs was 77.3%. Participants with longer duration of farming had higher numbers of MSDs. Almost part of pruning and harvesting postures in orchard farming were loaded works for musculoskeletal systems. Total DASH score was relatively high (14.9±14.4). Conclusions Almost orchardists have upper limb MSDs. Our results suggest the need to implement interventions in orchardists to prevent MSDs. References Gomez MI, Hwang S, Stark AD, May JJ, Hallman EM, Pantea CI. An analysis of self-reported joint pain among New York farmers. J Agric Saf Health. 2003;9:143–157. Holmberg S, Stiernstrom EL, Thelin A, Svardsudd K. Musculoskeletal symptoms among farmers and non-farmers: A population based study. Int J Occup Environ Health. 2002;8:339–345. Osborne A, Blake C, Fullen BM, Meredith D, Phelan J, McNamara J, Cunningham C. Prevalence of musculoskeletal disorders among farmers: A systematic review. Am J Ind Med. 2012;55(2):143-58. Acknowledgements This study was supported by a grant of the Center for Farmers Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. Disclosure of Interest None declared

THU0494 Prevalence and Characteristics of Hand Osteoarthritis in Korean Farmers: Influence of Farming Activity on Hand Osteoarthritis

Background Farming activity is burdened work with excessive use of hands. Thus, farmers are expected to have high prevalence of hand osteoarthritis (HOA). However, there is a lack of studies investigating prevalence and characteristics of HOA in Korean farmers. Objectives To estimate the prevalence of HOA among farmers in rural areas of Korea and assess whether HOA is related to farming activity. Methods The study was carried out from June 2013 to Dec 2014 with 700 farmers in Gyeong-nam Province of Korea. Clinical evaluation for hand joints was performed by rheumatologists and the plain radiographs of both hands were taken. The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) was used to assess symptoms and function of hand joints. Radiographic HOA was defined as Kellgren–Lawrence (KL) grade≥2 on plain radiographs and symptomatic HOA as KL grade≥2 with pain/aching/stiffness at the same joints. Severe HOA was defined KL grade≥3. Presence of HOA at individual level was defined as ≥1 affected joint. Results Participants comprised of 53% female and 47% male with mean age of 59.7±8.6 years. As divided types of growing crops, persimmon growers, strawberry growers, rice growers, and persimmon plus rice growers were 28.6%, 27.0%, 11.7%, 23.0%, respectively. The prevalence of radiographic, symptomatic, and severe HOA was 59.1%, 13.9%, and 24.4%, respectively. Finger joints were affected in 51.4% and thumb joints in 34.1%. Interestingly, male farmers showed high prevalence of radiographic HOA (55.9%) and symptomatic HOA (13.0%). The prevalence of HOA was similar in both hands and increased with longer duration of farming. Multiple logistic regression analysis showed a significant association of age, female sex, and body mass index with radiographic HOA. As adjusted for determinants above, rice growers were associated with an increased risk of HOA (odds ratio 3.5; 95% confidence interval 1.71 to 7.21). AUSCAN score was high in female and increased according to the severity of HOA. Conclusions The prevalence of HOA in male is high, and related to types of growing crops. Therefore, this study suggests that development of HOA is associated with farming activity. References Zhang Y, Niu J, Kelly-Hayes M, Chaisson CE, Aliabadi P, Felson DT. Prevalence of symptomatic hand osteoarthritis and its impact on functional status among the elderly: The Framingham Study. Am J Epidemiol. 2002;156(11):1021-7. Cho NH, Kim SH, Kim HA, Seo YI. The Prevalence and Risk Factors of Knee and Hand Osteoarthritis in Korea. Journal of Rheumatic Diseases. 2007;14(4):354-362. Acknowledgements This study was supported by a grant of the Center for Farmers Safety and Health, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. Disclosure of Interest None declared

THU0471 Myeloid Deletion of SIRT1 Suppresses Collagen-Induced Arthritis in Mice by Modulating Dendritic Cell Function

Objectives The type III histone deacetylase SIRT1 is a critical molecule in the modulation of immune and inflammatory response through the deacetylation of various histones and non-histone proteins. However, there are limited and controversial data regarding the roles of SIRT1 in rheumatoid arthritis (RA) and its role in dendritic cells (DCs) remains unknown. Thus, this study sought to assess the role of SIRT1 in collagen-induced arthritis (CIA) using a myeloid cell-specific SIRT1 knockout (mSIRT1 KO) mouse. Methods mSIRT1 KO mice were generated using the loxP/Cre recombinase system. CIA was induced in mSIRT1 KO mice and age-matched littermate loxP control mice. Arthritis severity was assessed by clinical, radiological, and pathological scoring. The levels of various cytokines in the joints, serum, lymph nodes were determined by quantitative polymerase chain reaction and ELISA. T cells and DCs were quantified using flow-cytometry and in vitro T cell cytokines and DCs markers were also measured. Results The mSIRT1 KO mice showed significantly lower arthritis severity and joint destruction compared with control mice. The expression of inflammatory cytokines, MMPs, and ROR-γT was also reduced in mSIRT1 KO mice. These effects were paralleled by reduction of Th1, Th17, CD69-positive T cells, CD80, and CD86 positive DCs in mSIRT1 KO mice. In addition, in vitro studies showed that interferon-γ and IL-17 production by T cells and the maturation of DCs were significantly decreased in mSIRT1 KO mice. Conclusions Unlike passive K/BxN serum transfer arthritis, myeloid cell-specific deletion of SIRT1 was associated with lower arthritis severity in CIA by modulating DCs maturation and Th1 and Th17 responses. The data suggest that SIRT1 plays a complex role in RA and careful investigation of cell-specific effects is necessary to delineate possible therapeutic uses of agents targeting SIRT1. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4188