W. G. Law

Enhanced expression of interferon-inducible protein-10 correlates with disease activity and clinical manifestations in systemic lupus erythematosus

Our objective was to investigate the serum levels of interferon‐inducible protein‐10 (IP‐10) in systemic lupus erythematosus (SLE) and their correlation with disease activity and organ manifestations. Serum IP‐10 levels were assessed in 464 SLE patients and 50 healthy donors. Disease activity was assessed by the revised SLE Activity Measure, and the concomitant active organ manifestations, anti‐ds DNA antibody titres, complement levels and erythrocyte sedimentation rates recorded. Peripheral blood mononuclear cell (PBMC) synthesis of IP‐10 in SLE patients and controls was determined by in vitro cultures stimulated with mitogen or lipopolysaccharide. Elevated serum IP‐10 levels were observed in SLE patients, which were significantly higher in the presence of active haematological and mucocutaneous manifestations. SLE PBMCs exhibited enhanced spontaneous IP‐10 production in vitro. Serial IP‐10 levels correlated with longitudinal change in SLE activity, even at low levels where anti‐dsDNA antibody and complement levels remain unchanged. These data demonstrate that IP‐10 levels are increased in SLE and serum IP‐10 may represent a more sensitive marker for monitoring disease activity than standard serological tests.

Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis

Ultrasonography is sensitive for synovitis detection but interobserver variation in both acquisition and image interpretation is still a concern. The objective was to assess if a short collegiate consensus would improve inter‐observer reliability in scoring of synovitis.

Urine sVCAM‐1 and sICAM‐1 levels are elevated in lupus nephritis

We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM‐1 (vascular) and sICAM‐1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity.

Major trends in the manifestations and treatment of rheumatoid arthritis in a multiethnic cohort in Singapore

We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990–1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8xa0years, respectively. The majority was female (84.1xa0%) and Chinese (76.6xa0%) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.

FRI0450 Predictors of Mortality in Systemic Sclerosis: The Singapore Scleroderma Registry

Background Although prognosis of systemic sclerosis (SSc) has improved significantly, the disease continues to cause excess mortality. Studies assessing mortality in SSc are lacking in Asia. Objectives We aim to describe the causes and evaluate predictors of mortality in Singapore Asian patients with SSc in a retrospective and inception cohort. Methods From 2008, patients diagnosed with SSc fulfilling the American College of Rheumatology (ACR)/EULAR1 or Very Early Diagnosis of Systemic Sclerosis (VEDOSS)2 criteria were recruited into the Singapore Scleroderma Registry. Demographics, disease manifestations and treatment for prevalent and incident cases seen at three tertiary rheumatology centers were collected using a standardized protocol. Mortality was verified with the national death registry up to 1 December 2013. In-hospital cause of death was determined by two independent reviewers according to categories set apriori. Person-years follow-up was calculated from date of cohort entry to either death or censor date. A univariate Cox proportional hazard (PH) regression was used to examine the association between each variable and mortality. Variables reported in the literature to associate with mortality and/or P value<0.1 were considered in the multiple Cox PH regression model. The forward stepwise selection approach and the Akaike Information Criterion were used to determine the multiple regression model, where age, gender and race were included as confounders. Results Of 349 SSc patients (87% females), 97% fulfilled the ACR/EULAR 2013 criteria (89% and 3% fulfilled 1980 ACR and VEDOSS criteria respectively). The mean age at diagnosis was 46.2 (SD 15) years, with 3216.2 person-years follow-up from initial SSc diagnosis or 740.6 person-years from cohort entry. Limited (LcSSc), diffuse (DcSSc) cutaneous SSc and SSc-overlap syndromes occurred in 35%, 38% and 26%, respectively. There were 35 deaths (10%) over 740.6 person-years follow-up, translating to a mortality rate of 47.3 per 1000 patient-years. Fifty-seven percent of deaths were SSc-related (interstitial lung disease [ILD, n=6], pulmonary arterial hypertension [PAH, n=6], gastrointestinal involvement [GI, n=3], renal crisis [n=2], cardiac [n=1] and others [n=2]). Multivariate analysis (n=275 with complete data set) (Table 1) showed that race (Indians had the highest hazards ratio [HR] for mortality compared to Chinese), smoking, disease subtype (SSc-overlap had the highest HR), baseline renal involvement, pulmonary artery systolic pressure (PASP) ≥40mmHg on echocardiography, and treatment with peripheral vasodilators or parenteral nutrition were independently associated with mortality. Conclusions PAH and ILD are leading causes of death in this Asian cohort. Disease subtype, race, renal involvement, PASP ≥40mmHg, smoking, and treatment with peripheral vasodilators or parenteral nutrition were independent predictors of mortality. References van den Hoogen F, et al. Ann Rheum Dis (2013), 72(11):1747-55. Matucci-Cerinic M, et al. Ann Rheum Dis (2009), 68(9):1377-80. Disclosure of Interest None declared

SAT0511 Achieving Consensus in Ultrasonography Synovitis Scoring in Rheumatoid Arthritis

Background Ultrasonography (US) is a sensitive method for synovitis detection in clinical practice but interobserver variation in both acquisition and image intepretation is still a key concern [1]. Various semiquantitative synovitis scoring methods have been proposed in the past for B-mode and PDUS. Recently, the OMERACT US Task Force also proposed the EULAR-OMERACT PDUS composite scoring which had moderate to excellent reliability [2]. However, this has not been tested formally outside of the steering group. Objectives The objective was to evaluate if a collegiate small group consensus would improve US synovitis assessment and scoring in patients with rheumatoid arthritis, in both still images and in image acquisition. Methods Eight rheumatologists from Singapore participated in a 1 day consensus meeting in November 2012, divided into (i) still-image interpretation and consensus followed by (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by OMERACT and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and EULAR-OMERACT PDUS composite score was assessed by intraclass correlation co-efficient (ICC). Agreement at the joint region level was calculated using prevalence-adjusted-biased-adjusted-kappa (PABAK). Results For B-mode still images, ICC was good at 0.75 (95%CI 0.66-0.82) while for PDUS images this was excellent; ICC=0.88 (95%CI 0.83-0.92). During image acquisition and interpretation, B-mode scoring showed ICC=0.75 (95%CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95%CI 0.48-0.72). The ICC for EULAR-OMERACT PDUS composite synovitis scoring was good at 0.77 (95%CI 0.68-0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and MTP, and no agreement at the knees (PABAK range -0.34 to 0.85). Conclusions A consensus meeting between colleagues was useful in improving interobserver variation in synovitis scoring by ultrasonography, but agreement in non-hand joints is still a problem, requiring further standardisation. References Cheung PP, Dougados M, Gossec L. Reliability of ultrasonography to detect synovitis in rheumatoid arthritis: a systematic literature review of 35 studies (1415 patients). Arthritis Care Res (Hoboken) 2010; 62:323-34. Naredo E, Wakefield R, Iagnocco A, et al. The OMERACT Ultrasound Task Force - Perspectives. J Rheumatol 2011;38:2063-7. Disclosure of Interest None Declared

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore

To measure the levels of B cell‐activating factor (BAFF) and endogenous anti‐BAFF autoantibodies in a cohort of multi‐ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age‐ and sex‐matched healthy controls were assayed for BAFF and anti‐BAFF immunoglobulin (Ig)G antibody levels by enzyme‐linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti‐BAFF‐IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti‐BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM‐R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820u2009±u200940 pg/ml and 152 pgu2009±u200945/ml, respectively [meanu2009±u2009standard error of the mean (s.e.m.), Pu2009<u20090·01], which were correlated positively with anti‐dsDNA antibody levels (ru2009=u20090·253, Pu2009<u20090·03), and SLAM‐R scores (ru2009=u20090·627, Pu2009<u20090·01). In addition, SLE patients had significantly higher levels of anti‐BAFF IgG, which were correlated negatively with disease activity (r = –0·436, Pu2009<u20090·01), levels of anti‐dsDNA antibody (r = –0·347, P < 0·02) and BAFF (r = –0·459, P < 0·01). The majority of patients in this multi‐ethnic Asian SLE cohort had elevated levels of BAFF and anti‐BAFF antibodies. Anti‐BAFF autoantibody levels correlated negatively with clinical disease activity, anti‐dsDNA and BAFF levels, suggesting that they may be disease‐modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti‐cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti‐cytokine therapies.