H.J. Baek

Osteopenia in men with mild and severe ankylosing spondylitis

We investigated the frequency and distribution of osteopenia according to the clinical severity in ankylosing spondylitis (AS). Bone mass was measured in men with mild (n=45) and severe AS (n=31) with dual-energy X-ray absorptiometry (DEXA). Definition of clinical severity was based on the Schober’s test. Osteopenia was commonly detected (48% in mild AS and 39% severe AS) and, in mild disease, more frequently observed at the lumbar spine than any of the proximal femur sites. In severe AS, however, the frequency of osteopenia at the femoral neck and Ward’s triangle was as high as at the lumbar spine. Both bone mineral density and T-scores in severe disease were lower than in mild disease at the femur neck, Ward’s triangle, and total proximal femur, but not in the lumbar spine. The progression of osteopenia may be reflected more reliably at proximal femur sites than at the lumbar spine.

Serum procalcitonin measurement for detection of intercurrent infection in febrile patients with SLE

It is sometimes difficult to distinguish infection from disease flare in febrile patients with systemic lupus erythematosus (SLE). Chill, leucocytosis, and increased C reactive protein (CRP) are known to be markers favouring infection.1 Procalcitonin (PCT) is the precursor of calcitonin and is synthesised in the parafollicular C cells of the thyroid. Serum PCT increases in severe bacterial or fungal infection but does not increase, or increases only slightly, in viral infections.2 3 The purpose of this study was to evaluate the usefulness of serum PCT in febrile episodes of patients with SLE to distinguish infection from disease flare.nnWe prospectively enrolled 19 patients with SLE with fever who were admitted to Seoul National University Hospital between October 1998 and April 1999. Fever was defined as an axillary temperature over 38°C. Eleven patients with inactive SLE were enrolled as controls. Blood of the febrile lupus patients was withdrawn three times: on the day of the hospital visit, and after 24 hours and 48 hours. Another sample was withdrawn two weeks after defervescence to control infection or because of a decrease in lupus activity. At the detection of fever, blood cultures and other necessary cultures were performed with complete blood count, Westergren erythrocyte sedimentation rate (ESR), CRP, serum anti-dsDNA, complements …

Efficacy and safety of PG201 (Layla(®)) and celecoxib in the treatment of symptomatic knee osteoarthritis: a double-blinded, randomized, multi-center, active drug comparative, parallel-group, non-inferiority, phase III study.

The objectives of the study are to demonstrate the non-inferiority of PG201 (Layla®) 600xa0mg in comparison with celecoxib 200xa0mg for the treatment of symptomatic knee osteoarthritis (OA). In total, 309 patients were randomly assigned to receive either the test drug, PG201 600xa0mg (nxa0=xa0154) or celecoxib 200xa0mg (nxa0=xa0155). The primary efficacy variable was improvement in mean 100-mm pain VAS score from baseline to the final visit (week 8), and this value was compared between the 2 treatment groups. Secondary outcome variables included changes from baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain VAS score and subscale score, patient’s global assessment of disease status quality of life (short form-36) and responder index at weeks 4 and 8. For safety assessment, adverse events were recorded at each clinical visit. At weeks 8, the 100-mm pain VAS scores were significantly decreased in patients receiving both PG201 600xa0mg (pxa0<xa00.0001) and celecoxib 200xa0mg (pxa0<xa00.0001) as compared to the baseline scores; however, no statistically significant differences in these values were noted between the groups (pxa0=xa00.312). These results met pre-specified criteria for non-inferiority for both the intent-to-treat and per-protocol populations. PG201 600xa0mg and celecoxib 200xa0mg were both well tolerated and no statistically significant differences in the tolerability profile between the groups. PG201 600xa0mg was as effective and safe as celecoxib 200xa0mg in the treatment of symptomatic knee OA and might be a useful new medication for the treatment of symptomatic knee OA.

Induction of Remission is Difficult due to Frequent Relapse during Tapering Steroids in Korean Patients with Polymyalgia Rheumatica

Polymyalgia rheumatica is an inflammatory disease affecting elderly and involving the shoulder and pelvic girdles. No epidemiological study of polymyalgia rheumatica was conducted in Korea. We retrospectively evaluated patients with polymyalgia rheumatica followed up at the rheumatology clinics of 10 tertiary hospitals. In total 51 patients, 36 patients (70.6%) were female. Age at disease onset was 67.4 yr. Twenty-three patients (45.1%) developed polymyalgia rheumatica in winter. Shoulder girdle ache was observed in 45 patients (90%) and elevated erythrocyte sedimentation rate (> 40 mm/h) in 49 patients (96.1%). Initial steroid dose was 23.3 mg/d prednisolone equivalent. Time to normal erythrocyte sedimentation rate was 4.1 months. Only 8 patients (15.7%) achieved remission. Among 41 patients followed up, 28 patients (68.3%) had flare at least once. Number of flares was 1.5 ± 1.6. The frequency of flare was significantly lower in patients with remission (P = 0.02). In Korea, polymyalgia rheumatica commonly develops during winter. Initial response to steroid is fairly good, but the prognosis is not benign because remission is rare with frequent relapse requiring long-term steroid treatment.

THU0179 Discontinuation of Nonsteroidal anti-Inflammatory Drugs in Rheumatoid Arthritis Patients with Low Disease Activity

Background Although nonsteroidal anti-inflammatory drug (NSAIDs) is effective in relieving joint pain in rheumatoid arthritis (RA) patients, long-term use of NSAIDs can cause adverse effects on gastrointestinal or cardiovascular organs. When patients discontinue daily use of NSAIDs, there is often a dichotomous clinical response in patient-reported outcomes (PRO). Objectives We aimed to examine the clinical outcome especially joint pain, and its associated factors in RA patients with low disease activity (LDA) after discontinuing NSAIDs. Methods This study was a 16-week, multi-center prospective open-label trial conducted at eight rheumatology clinics in Korea. RA patients who achieved LDA (DAS28 <3.2) who were on NSAIDs for more than 2 consecutive months, discontinued the NSAID. Acetaminophen (AAP) was used as the rescue medication. During the study period, changes of DAS28 and PRO including pain visual analogue scale (VAS) and Routine Assessment of Patient Index Data 3 (RAPID-3) score were assessed. NSAIDs were restarted when patients 1) pain was uncontrolled with AAP and 2) PRO were aggravated. The endpoint was to analyze the group of patients who continued to withdraw NSAIDs within the study period. Patients were further classified to have “sustained effectiveness” who met the following: 1) 16-week pain VAS ≤30 mm or increase less than 20% from baseline and 2) 16-week RAPID-3 score ≤6 or increase less than 20% from baseline. Results A total of 121 RA patients with LDA were enrolled in the study. Four patients were lost to follow-up. At the end of the study, 18 (15.3%) patients had restarted NSAIDs owing to uncontrolled pain. In general, there was a difference in pain VAS between baseline (median 15 mm (IQR 5–20)) and 16 weeks (median 17 mm (IQR 5–40)) (p=0.022). Changes of DAS28 and RAPID-3 were insignificant in patients taking on-demand AAP (n=99) (0 versus 16 weeks; DAS28, p=0.111; RAPID-3; p=0.339). Moreover, 60% of the total patients (73/117) ended up to show sustained effectiveness without restarting NSAIDs. By using a multivariate logistic regression model, we found out that joint swelling was the detrimental factor compromising sustained effectiveness (OR 0.312, 95% C.I. 0.125–0.777, p=0.012). Conclusions Discontinuation of NSAIDs can be attempted in RA patients with LDA, especially in those without swollen joints at the time point of its cessation. Disclosure of Interest None declared

AB0577 Mean Platelet Volume is Associated with Behcet's Disease Activity

Background Mean platelet volume (MPV) has been known to be a marker of platelet activity and influenced by inflammation.The correlations of MPV with disease activities were reported in several rheumatic diseases such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. However MPV is controversial as a marker of their disease activities. Furthermore, the association of MPV with disease activity in Behcets disease (BD) is not determined yet. Objectives The aim of this study is to investigate the association of MPV with clinical manifestations and disease activity in BD. Methods We sequentially retrieved data on 193 patients with BD who visited to our rheumatic clinic from 1999 to 2013 by reviewing of medical records. BD was diagnosed according to International Criteria for BD. The data on demographics, clinical manifestations, and laboratory results including MPV, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were collected. Active BD was defined as it needed prednisolone of more than 0.5 mg/kg/day or to add immunosuppressive agents. Infection was demonstrated by culture or clinical improvement with antibiotic treatment. Statistical analysis was made by t-test and Pearsons correlation. A value of p<0.05 was considered as statistically significant. Results The ratio of female to male was 2:1 and the age of symptom onset was 32.2±11.1 years. The age at diagnosis of BD was 40.9±10.0 years and the follow-up duration was 4.7±3.8 years. Fifty-one patients (26.4%) had major organ involvements such as eye (17.6%), gastrointestinal (7.8%), vascular (4.7%) and nervous system (3.1%). MPV at diagnosis was 8.2±1.2 fl. MPV was not related with clinical manifestations, ESR and CRP. During follow-up, 79 patients had active BD and 12 patients had infections such as pulmonary tuberculosis and pyelonephritis. MPV in active BD (8.1±1.4 fl) was lower than that in inactive disease (8.9±1.3 fl; (p<0.0001). MPV significantly increased when the patients were infected (9.5±1.6 fl; p<0.0001) Conclusions MPV was not related with clinical manifestations of BD. However, there was an association of active BD with lower MPV and of infection with higher MPV. Thus, MPV level may be used as a marker of BD activity and to differentiate infection from active BD. References Are platelet volume indices of clinical use? A multidisciplinary review. Ann Med. 2012 Dec;44(8):805-16. Mean platelet volume in recurrent aphthous stomatitis and behcet disease. Angiology. 2014 Feb;65(2):161-5. Increased mean platelet volume in Behçets disease with thrombotic tendency. Tohoku J Exp Med. 2010 Jun;221(2):119-23. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5121

Acquired enophthalmos with systemic lupus erythematosus

Ocular involvement sometimes occurs with systemic lupus erythematosus (SLE) but enophthalmos with SLE is rare. We report a case of enophthalmos with SLE. A 25-year-old male was admitted for two weeks of fever, sore throat, arthralgia, chest pain and right arm weakness with pain. We diagnosed him with SLE with malar rash, arthritis, pleural effusion, proteinuria, leukopenia, positive antinuclear antibody, anti-dsDNA, and lupus anticoagulant. The patient was prescribed high-dose prednisolone and hydroxychloroquine 400u2009mg. One week after discharge, he complained about a sensation of a sunken right eye. CT showed right enophthalmos, a post-inflammatory change and chronic inflammation. Proteinuria increased to 3.8u2009g/day after the patient stopped taking prednisolone. Cyclophosphamide therapy was administered for three months without improvement. We decided to restart prednisolone and change cyclophosphamide to mycophenolate mofetil. Proteinuria decreased but enophthalmos remains as of this reporting.

FRI0080 Effects of IL-6 Receptor Inhibition Therapy on The Serum Levels of IL-33 and IL-6 in Patients with Rheumatoid Arthritis

Background Several pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, IL-8 and IL-15 are known to be critical in synovial inflammatory process in RA and successful results have been obtained in RA treatment with targeting pro-inflammatory cytokines including TNF-α, IL-1 and IL-6. Objectives This study sought to investigate the role of IL-33 and IL-6 in RA patients receiving IL-6 receptor inhibition therapy. Methods We analyzed the association of the IL-33 and IL-6 level with disease activity and serologic features in 83 patients with RA. We also measured the serum level of IL-33 and IL-6 before and after the administration of tocilizumab for 24 weeks in 40 patients. Results Serum IL-33 level showed significant correlation with RF (rho =0.660, p<0.001) but did not correlate with DAS28, ESR, hsCRP or RA duration. IL-6 level was significantly correlated with hsCRP (rho =0.482, p<0.001) but not correlate with DAS28, ESR, RF or RA duration. There was no correlation between serum IL-6 and IL-33 levels. Serum IL-33 level significantly decreased after 24 weeks of IL-6 receptor inhibition in patients with RA (p<0.001). When comparing subgroups according to ACR20 response, serum IL-33 levels were significantly decreased after 24 weeks of IL-6 receptor inhibition therapy in ACR20 responders (p<0.001) but not in the non-responders (p=0.084). Baseline IL-33 levels were not significantly different between the two subgroups (p=0.765). Serum IL-6 levels were not significantly changed after 24 weeks of IL-6 receptor inhibition therapy (median 7.1 to 8.9 pg/mL, p=0.503). Changes of IL-6 levels were insignificant both in ACR20 responders and non-responders after 24 weeks of IL-6 receptor inhibition therapy. Baseline IL-6 levels were not different between ACR20 responders and non-responders. Conclusions The use of IL-6 receptor inhibitor decreased the serum level of IL-33 and this effect seems to be led by the responder group. IL-33 could be a useful indicator to monitor the response in IL-6 receptor inhibition therapy. 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

SAT0059 Baseline Interleukin-17A PREDICT Treatment Response to TOCILIZUMAB and Disease-Modifying Antirheumatic Drugs Therapy

Background Tocilizumab (TCZ) has been developed and investigated in several clinical trials for efficacy and adverse events in RA patients. But it remains to be investigated which biomarkers have early predictive values. Objectives To investigate predictive cytokines of TCZ therapy in rheumatoid arthritis (RA) patients with an inadequate response to disease-modifying antirheumatic drugs (DMARDs). Methods We collected sera as part of CWP-TCZ301, a 24-week, randomized, double–blinded trial of TCZ in RA patients with an inadequate response to DMARDs. Serum levels of cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-17A, IL-21 and IL-23 were determined by luminex multiplex analysis at baseline and after treatment (4, 12 and 24 weeks). IL-6 and soluble IL-6 receptor (sIL-6R) were measured by ELISA. Therapeutic response was evaluated by American College of Rheumatology 20% improvement (ACR20) in the TCZ group (n=47) and placebo group (n=48) after 24 weeks. Results Early withdrawal patients from the study were excluded in the evaluation. In TCZ group (n=40), 29 patients were ACR20 responders and 11 patients were non-responders after 24 weeks of treatment. Baseline serum levels of IL-17A were significantly lower in responders than in non-responders (p <0.05). However IL-17A level did not significantly change during TCZ treatment irrespective of ACR20 response. Levels of IL-21 and IL-23 were not significantly different at baseline in responders and non-responders. However, they were significantly decreased at 12 and 24 weeks in responders (all p <0.005), but not in the non-responders. In the placebo group (n=43), 8 patients were ACR20 responders and 35 patients were non-responders after 24 weeks of treatment. Baseline serum levels of IL-17A and IL-21 in ACR20 responders were significantly lower than in non-responders (p<0.001 and p=0.001, respectively). But they did not significantly change during DMARDs treatment, irrespective of ACR20 response. Multivariable logistic regression analysis showed that lower baseline IL-17A patients had increased the odds ratio of being a responder after TCZ (OR 7.364) as well as placebo (OR 9.333) treatment. Figure 1. ROC curve analyses for ACR responders after TCZ (A) and DMARDSs (B) therapy. Conclusions Baseline serum level of IL-17A could be used to predict response of TCZ and DMARDs therapy in RA patients. References Zhou L, Ivanov, II, Spolski R, Min R, Shenderov K, Egawa T, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 2007;8(9):967-74. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5095