W.-H. Yoo

Use of tocilizumab in a patient with pyoderma gangrenosum and rheumatoid arthritis.

neighbours like Hungary, which is more similar to Poland or Czech Republic. According to the Ministry of Health statistics, in Romania psoriasis affects about 1–2% of the population (approximately 400 000 patients). Reimbursement for biological therapies is made by the National Health Insurance House and there is no limit regarding the number of beneficiaries. During 2014, about 2700 patients (0.25% of all psoriasis patients) have benefited. This year (2015), a national registry for psoriatic patients was developed. Every dermatologist will be able to introduce the patients they treat. Romania has a high rate of patients reimbursed for biologic treatment and this happens in a country with the highest incidence of tuberculosis (TB) infection in Europe (approximately 80/100 000 inhabitants according to WHO/Europe, HFA Database, July 2013). This problem should be better monitored and managed, because there is a high risk of spreading the infection in Europe, with cases of multidrug-resistant TB. The psoriatic patients also undergo chemoprophylaxi in case of latent TB, which is sometimes useless and with adverse reactions, even if it does not seem to influence the therapy response. Just one biological therapy family is covered by the insurances – the TNF blockers, but in some cases they stop working properly and a switch to another class of biologic treatment would be recommended. We had a few patients treated with ustekinumab, but this was funded by Johnson&Johnson Company, and also a small number of patients treated with efalizumab through some local and pharmaceutical co-funding. We also have some centres with ongoing studies on ixekizumab and secukinumab with good results. The majority of Romanian dermatologists tend to resort to topical treatment, although in most cases this is not effective in moderate to severe psoriasis cases and a systemic approach would be recommended; psoriasis being a systemic disease. In Romania, every dermatologist is entitled to recommend and treat with biologics but he/she must follow the protocol for biologic treatment of psoriatic patient. Because there is a reluctance of dermatologists regarding systemic treatment in psoriasis and for biologics, it would be more appropriate to develop centres with experience in treating a greater number of psoriatic patients with biologics. When biological therapy programmes started in different countries at different times, the enrolment was exaggerated during the initial years because there was a high need/burden for these therapies, but this pressure diminished with time. Now the pressure is on new family biologics, as the TNF blockers usually loses efficiency in time and adverse reactions appear. But similar to other chronic inflammatory conditions treated with biological therapies, the approval for insurance coverage is very hard to obtain. We would not expect more coverage for patients treated with biosimilars because the difference in price in the end is not significant, about 10%. Treating moderate to severe psoriasis with biologics is beneficial to the patients and a wide access should be offered, but the programmes of reimbursement need to be upgraded in real time because many factors like patients’ preferences, community, social and even financial aspects need to be taken into account.

45 Induction of differentiation of regulatory t cells coupled to endoplasmic reticulum stress in patients with systemic lupus erythematosus

Background and aims The aim of this study was to investigate the proportion of regulatory T cells (Tregs) in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) compared with that of healthy controls (HCs). We also evaluated the differentiation difference of induced Tregs in vitro under the presence or absence of endoplasmic reticulum (ER) stress, which is one of the causal factors triggering lupus flares. Methods We isolated the PBMCs of 16 SLE patients and 11 HCs. The percentage of CD4+CD25+FoxP3+ Tregs was analyzed using flow cytometry. The PBMCs were incubated with anti-CD3/CD28 beads, supplemented with transforming growth factor-β and interleukin-2 to induce differentiation of Tregs, with or without tunicamycin for 36 hours. Results The percentage of Tregs in the PBMCs of SLE patients was lower than that in the HCs (1.8 ± 0.9 versus 2.6 ± 0.7%, p=0.02). The induced differentiation of Tregs increased in both groups, and the increased proportion was greater in the SLE group (600 ± 351 versus 252 ± 95%, p=0.01). Incubation with tunicamycin in the Treg differentiation process also increased the proportion of Tregs in both groups (385 ± 259 versus 166 ± 105%, p=0.006), and the increased proportion was higher in the SLE group. Conclusions The baseline percentage of Tregs was lower in SLE patients than in HCs. However, when Treg differentiation was induced, the differentiation of Tregs was more pronounced in the SLE group. This exaggerated differentiation may reflect the paradoxical response to the diminished suppressive capacity of Tregs in SLE patients.

207 Subclinical deterioration of left ventricular diastolic function in systemic lupus erythematosus

Background and aims Systemic lupus erythematosus (SLE) represents diverse cardiac manifestation, but diastolic dysfunction has been reported infrequently. This study is aimed to investigate the left ventricular diastolic function and the factors related in SLE patients compared with healthy controls. Methods Thirty consecutive female SLE patients without evidence of cardiac disease were underwent standard transthoracic echocardiography, and were compared with 30 age-matched healthy female controls. Patient characteristics, organ damage and laboratory data were retrieved by medical chart review. Results In SLE patients, indexes of LV diastolic function differed from control group, with reduced early diastolic filling velocity (E), as well as prolongation of the time taken from the maximum E point to baseline, reduced ratio of early to late diastolic flow velocity (E/A), prolonged ratio of E to early diastolic mitral annular velocity (E’) (E/E’). However, the differences did not show statistical significance. Anti-Ro antibody positivity was observed in 43% of SLE patients, and it was correlated with higher E/A ratio significantly (1.3±0.4 vs 1.0±0.2, p=0.03). In addition, the SLE patients with hematologic or renal involvement showed more enlarged size of left atrium significantly compared to the patients without any involvement (36±4.3 vs 31±9.2, p=0.01). Conclusions Although not statistically significant, there was a trend which suggested that patients with SLE have subclinical impaired diastolic function compared with the healthy control. Presence of anti-Ro antibody and systemic organ involvement was related with the diastolic dysfunction markers.

AB0651 Usefulness of Neutrophil To Lymphocyte Ratio in Prediction of Lung Involvement in Patient with Systemic Sclerosis

Background Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) are reported to be increased in various inflammatory diseases, but there clinical significance in systemic sclerosis (SSc) remains unclear Objectives The aim of the study is to evaluate usefulness of neutrophil to lymphocyte ratio in diagnosis of systemic sclerosis and in prediction of lung involvement such as pulmonary fibrosis. Methods The medical records of 88 SSc patients and 50 healthy controls were retrospectively reviewed. NLR, PLR between SSc patients and healthy controls were compared, and correlation between these indexes and lung involvement were analyzed. Exclusion criteria included active infection and/or the presence of any hematological, cardiovascular or metabolic disorder. Results The NLR and PLR were found to be significantly higher in SSc patients when compared to the healthy control (NLR: 3.95±6.59 vs 2.00±1.07, p<0.01, PLR: 163.87±101.12 vs 126.33 ±42.31, p<0.05). SSc patients with lung involvement had higher NLR and PLR levels than those without lung involvement (p<0.01, p<0.05). NLR was negatively correlated with forced vital capacity (FVC)(r=-0.341, p<0.01) but not diffusing capacity for carbon monoxide (DLCO). Receiver-operating characteristics analysis (ROC) of NLR to predict lung involvement in SSc showed that the area under the curve (AUC) was 0.763. The cut-off NLR value for prediction of lung involvement was determined as 2.59. (sensitivity, 0.700;specificity, 0.729; p<0.01) Conclusions NLR may be a promising marker that reflects lung involvement in patients with SSc and values greater than 2.59 were useful in prediction of lung involvement. Disclosure of Interest None declared

AB0929 Neutrophil/lymphocyte Ratio (NLR), Platelet/lymphocyte Ratio (PLR) Were Useful Markers in Assessment of Inflammatory Response in Aosd Patients

Background Both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) are reported to be increased in various inflammatory diseases, but there clinical significance in adult onset still disease (AOSD) remains unclear. Objectives The aim of the present study was to evaluate NLR and PLR as a inflammatory marker in AOSD. Methods The medical records of 23 AOSD patients and age, sex-matched 25 healthy individuals were retrospectively reviewed. NLR, PLR between AOSD patients and healthy controls were compared, and correlation between these indexes and clinical characteristics were analyzed. Exclusion criteria included active infection and/or the presence of any hematological, cardiovascular or metabolic disorder. Results The NLR and PLR were found to be significantly higher in AOSD patients when compared to the healthy control (NLR: 10.67± 6.73 vs 2.05±1.07, p<0.001, PLR: 255.78±107.22 vs 128.10 ±42.60, p<0.001). The NLR and PLR were decreased significantly after treatment (4.67±3.22, 196.84±78.54). NLR was positively correlated with erythrocyte sedimentation rate (ESR)(r=0.612, p<0.001), C-reaction protein (CRP)(r=0.597, p<0.001) and ferritin (r=0.552, p<0.001). PLR was positively correlated with ESR (r=0.648, p<0.001), CRP (r=0.536, p<0.001) except ferritin (r=0.33, p=0.025). Conclusions NLR, PLR, together with other serum inflammatory markers, were proving as significant clinical tools which could be used as biomarkers for inflammatory response of disease activity in AOSD patients. Disclosure of Interest None declared

THU0075 Tacrolimus Regulates the Expression of Endoplasmic Reticulum Stress-Mediated Osteoclastogenesis and Inflammation in Vitro and in Collagen-Induced Arthritis Mouse Model

Background Tacrolimus is a T cell specific, anti-inflammatory agent that has been used as a therapeutic agent for rheumatoid arthritis (RA). IL-1b- and thapsigargin (TG)-induced endoplasmic reticulum (ER) stress modulates the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis. Objectives This study was aimed at defining the effect of tacrolimus on endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation and to elucidate the underlying mechanisms. Methods Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to differentiate them into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1β, TG, or TAC. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. Collagen-induced arthritis (CIA) was induced by immunization of female Lewis rats with an emulsion of bovine type II collagen and incomplete Freunds adjuvant. Lesions of bone and cartilage were assessed on the basis of histological changes in the knee joint and radiographic analysis of the hind paw. Tacrolimus at doses of 3.2 mg/kg or its placebo formulation was orally administered to rats for 28 days from the day after immunization. We examined the histopathological changes of osteolysis and the expression of specific ER stress-mediated inflammatory signaling pathway biomarkers (IRE1α, GRP78/Bip, c-Fos, and NF-κB). In addition, pro-inflammatory cytokines and osteoclastogenic molecules (RANKL, and M-CSF) were assessed in the knee and ankle joints in the CIA mouse model. Results In vitro, IL-1b- and thapsigargin (TG)-induced endoplasmic reticulum stress modulates the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis. In the mouse model, tacrolimus administration resulted in a dramatic amelioration of osteolysis and significant reduction in ER stress intensity. Simultaneously, tacrolimus lessened inflammatory cell infiltration, reduced the capability of osteoclastogenesis, and reduced the inflammatory response by reducing the levels of IRE1α, GRP78/Bip, c-Fos, and NF-κB. Conclusions These findings suggest that tacrolimus has the potential to inhibit the progression of joint damage by inhibiting endoplasmic reticulum stress as well as anti-inflammatory effects in established RA. Disclosure of Interest None declared

AB0889 Massive Elimination of Multinucleated Osteoclasts by Eupatilin is Due to Dual Inhibition of Transcription and Cytoskeletal Rearrangement

Background Osteoporosis is an ageing-associated diseases requiring better therapeutic modality. Eupatilin is a major flavonoid from Artemisia. Objectives We aimed to evaluate the effects of eupatilin on RANKL-induced osteoclast differentiation and its mechanism of action. Results Upon stimulation prior to nuclear factor κB (RANK)-ligand (RANKL) treatment or poststimulation of bone marrow macrophages (BMCs) in the presence of RANKL with eupatilin complete blockade of RANK-dependent osteoclastogenesis was accomplished. This blockade was accompanied by inhibition of rapid phosphorylation of Akt, GSK3b, ERK and IkB as well as downregulation of c-Fos and NFATc1 at protein levels, suggesting that transcriptional suppression is a key acting mechanism on the anti-osteoclastogenesis. Transient reporter assays or gain of function assays confirmed that eupatilin was, indeed, a potent transcriptional inhibitor in osteoclasts (OC). Surprisingly, when multinucleated osteoclasts (MNCs) were cultured on bone scaffolds in the presence of eupatilin bone resorption activity was also completely blocked by dismantling actin ring, suggesting that another major acting site of eupatilin is cytoskeletal rearrangement. The eupatilin-treated MNCs revealed a shrunk cytoplasm and accumulation of multi-nuclei, eventually becoming fibroblast-like cells. No apoptosis occurred. Inhibition of phosphorylation of cofilin by eupatilin suggests that actin may play an important role in the catastrophic morphological change of MNCs. Human OC were similarly responded to eupatilin. When eupatilin was administered to LPS-induced osteoporotic mice after manifestation of osteoporosis, it was capable of preventing bone loss. The ovariectomized (OVX) mice remarkably exhibited bone protection effects. Conclusions Taken together, eupatilin is an effective versatile therapeutic intervention for osteoporosis as dual blockaders; 1) transcriptional suppression of c-Fos and NFATc1 of differentiating OC and 2) inhibition of actin rearrangement of pathogenic MNCs. 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

SAT0286 Monthly Ibandronate Reduces Bone Loss in Osteopenic Women with Rheumatoid Arthritis Receiving Long-Term Glucocorticoids: A 48-Week Double-Blinded Randomized Placebo-Controlled Investigator-Initiated Trial

Background Long-term use of glucocorticoids (GC) is problematic for patients with increased risk for vertebral fractures, especially those with rheumatoid arthritis (RA). Thus, prevention of GC-induced osteoporosis (GIOP) with bisphosphonates has now become an important strategy for reducing morbidity in RA patients. Ibandronate is indicated for the treatment and prevention of osteoporosis in postmenopausal women. However, evidence for ibandronate in GIOP prevention has been insufficient to date. Objectives To investigate efficacy of monthly ibandronate in RA women with reduced bone mineral density receiving long-term GCs Methods Female RA patients meeting the 1987 ACR classification criteria were enrolled in this 48-week double-blinded randomized placebo-controlled trial (clinicaltrials.gov NCT01287533). Patients that had taken GC (prednisolone-equivalent dose of ≥5 mg) for 3 or more consecutive months and fulfilling L1-4 T-score of < -1.0 and ≥ -2.5 by dual-energy X-ray absorptiometry were enrolled in this study. Patients were divided into 2 groups: 150 mg ibandronate versus placebo po every 4 weeks. Both groups were provided with daily 1500 mg of calcium carbonate and cholecalciferol of 400 IU. The primary end point was to compare the % changes of the L1-4 T-score at 48 weeks compared with baseline. Results Two hundred eleven patients from 13 centers nationwide participated in this study. One hundred sixty seven patients were randomized. The mean age of patients in the ibandronate and placebo group were 54.5 and 55.1 years, respectively. Baseline characteristics were not dissimilar between the 2 groups. The result of the primary endpoint is shown below (table). Serum C-terminal telopeptide was significantly reduced at 48 weeks in the ibandronate group. There was no incident of fracture in both groups during the study period. Safety profiles including adverse events were comparable between the 2 groups. Conclusions Monthly ibandronate for 48 weeks is effective in reducing bone loss in RA women on long-term glucocorticoids. Longer follow-up studies would be needed to investigate the effect on fracture prevention. Acknowledgements We would like to thank CTC bio for manufacturing the placebo, and Mr. Je-suk Kim for aiding statistical analyses. 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