E. T. Koh

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.

Discordant assessment of lupus activity between patients and their physicians: the Singapore experience

Patients with systemic lupus erythematosus often assess their disease activity differently from their physicians. We studied the factors associated with this discordance. The data provided by 534 systemic lupus erythematosus patients were analyzed. We compared the physician and patient assessments of lupus activity on a visual-assessment scale from the same visit. We collected clinical data and scores from MOS 36-Item Short-Form Health Survey, Systemic Lupus Erythematosus Quality-of-Life Questionnaire, Rheumatology Attitudes Index, Systemic Lupus Erythematosus Disease Activity Index, and revised Systemic Lupus Activity Measure. Patients tended to score their disease activity higher than do their physicians, when these factors were present: poorer general health assessment, presence of thrombocytopenia, hypertension and urinary sediments, and difficulty in carrying groceries. Physicians tended to score the disease activity higher than do the patients in these circumstances proteinuria, hemolysis, use of azathioprine or cyclophosphamide, tiredness, photosensitivity, higher revised Systemic Lupus Activity Measure score, casturia, and patient report of being more easily ill than are other patients. There was only moderate correlation between the discordance in the baseline and the subsequent visits. The physician assessment of disease activity at baseline correlated better with an objective measure of disease activity (revised Systemic Lupus Activity Measure) in the subsequent visit than the patient assessment. In conclusion, discordance in the perception of disease activity between patients and physicians may be amenable to intervention.

SLE mortality in an oriental population

We analysed the causes of 67 deaths, over a 4 y period, in our oriental population with systemic lupus erythematosus (SLE). The median disease duration was 48±60.5 months (range 1—250 months). The mean age at diagnosis and death were 30 and 35.1 y respectively. SLE alone accounted for death in 30 patients (44.8%), infection in 27 (40.3%), pulmonary embolism in 5 (7.5%), malignancy in 4 (5.9%) and rheumatic heart disease in 1 (1.5%). The major organ involvement in those with active disease at death were SLE related thrombocytopenia (n = 23/44, 52.3%), nephritis (n=21/44), 47.7%), cerebral lupus ( n=16/44, 36.4%), and pulmonary haemorrhage (n=12/44, 27.3%). As in other series, SLE and infection were the principal causes of death in our population. During this 4 y period, there was no late death due to atherosclerosis.

Cyclophosphamide type I hypersensitivity in systemic lupus erythematosus

Cyclophosphamide is an important immunosuppressive agent in the treatment of many rheumatic diseases. Urticaria and anaphylaxis to intravenous cyclophosphamide (i.v. CYC) have been reported in patients with haematological and solid organ malignancies. This is the first report in the rheumatology literature of a type I hypersensitivity reaction following monthly i.v. CYC. An 18-year-old girl with systemic lupus erythematosus (SLE) developed generalized urticaria (without concomitant angioedema or anaphylaxis) following i.v. CYC. She had previously developed life threatening angioedema following a respiratory tract infection. She successfully completed regular pulse i.v. CYC with pre-medication with anti-histamine. In the absence of a severe type I hypersensitivity reaction and other suitable immunosuppressive agents, i.v. CYC may be safely continued with pre-medication and careful monitoring during each infusion.

Comparison of elderly- and young-onset rheumatoid arthritis in an Asian cohort

To describe the demographic characteristics, clinical features, functional status and quality of life of elderly‐onset (EORA) and young‐onset (YORA) rheumatoid arthritis (RA) patients in an Asian cohort.

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 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti‐dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM‐R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti‐BAFF IgG, which were correlated negatively with disease activity (r = –0·436, P < 0·01), 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.

THU0116 Singapore Patients with Rheumatoid Arthritis Have A Higher Incidence of Solid-Organ Malignancies than The General Population: Findings from The TTSH RA Registry

Objectives Patients with rheumatoid arthritis (RA) have been shown to have an increased risk of developing malignancies. This study was undertaken to determine the incidence and patterns of malignancy in RA patients and identify risk factors of malignancy among patients with RA. Methods Patients from the TTSH RA Registry were followed up longitudinally and those who developed malignancies from 2001 to 2013 after the onset of RA were identified. Age-standardised rates (ASRs) of various cancers were analyzed and compared with the Singapore Cancer Registry data. Risk factors for developing malignancy, including demographics and disease characteristics at baseline, were analyzed using Chi-squared test and students t test. Results Of the 1,134 patients in the registry, 28 patients were excluded as they developed malignancy prior to study enrollment. 1,106 patients were included in the final analysis. Of the 1,106 patients, 81 patients developed malignancies at a mean interval of 15.1 (SD 9.7) years after the onset of RA. The mean age of the 81 patients was 65.9 (SD 10.8) years, of which 61 (75.31%) were females and 69 (85.19%) were Chinese. There were 70 (86.4%) with solid-organ tumours and 11 (13.6%) haematological malignancies. The ASR of cancer in RA patients was 310.3 for males and 232.5 for females per 100,000 person-years, compared with 229.3 (95%CI 226.5–232) for males and 218.3 (95%CI 213.8–216.3) for females in the general population. By cancer type, there is an increased risk of lung cancer, lymphoid neoplasms and stomach cancer in RA compared with the general population. The risks factors for developing malignancy (p<0.05) include male gender, non-Indian ethnicity, onset of RA at an older age, untreated RA and higher disease activity.Table 1. Demographics, disease characteristics and treatment history of patients without malignancy and those who develop malignancy Total No. of patients No. of patients without maligancy No. of patients with maligancy after 1st study entry Univariate test n=1106 (%) n=1025 (%) n=81 (%) p-value (t-test or chi2) Demographics  Age at RA onset (yrs) mean (SD) 45.03 (13.40) 44.58 (13.20) 50.77 (14.59) 0.0001  Age at RA diagnosis (yrs) mean (SD) 47.31 (13.69) 46.74 (13.55) 54.43 (13.52) <0.0001  Duration of RA onset to RA diagnosis (mths) mean (SD) 27.34 (66.63) 26.02 (64.86) 43.96 (84.61) 0.0196  Gender Male 177 (16.02) 157 (15.33) 20 (24.69) 0.0390 Diease characteristics  ESR at 1st study visit mean (SD) 37.58 (27.06) 36.98 (26.60) 45.15 (31.54) 0.0102  CRP at 1st study visit mean (SD) 20.23 (23.21) 19.11 (22.24) 33.56 (30.59) 0.0248  No. of tender joints at 1st study visit mean (SD) 1.84 (3.80) 1.78 (3.69) 2.54 (4.94) 0.0817  No. of swollen joints at 1st study visit mean (SD) 2.34 (3.59) 2.26 (3.45) 3.37 (4.90) 0.0072  DAS28 at 1st study visit mean (SD) 3.35 (1.41) 3.33 (1.39) 3.61 (1.57) 0.0894 Conclusions The incidence of solid-organ malignancies was higher than hematological malignancies, unlike that in the literature. The overall risk of malignancy is higher in RA patients. Chronic inflammation from RA is associated with increased risk of malignancy. Acknowledgement This study is supported by the Centre Grant, National Medical Research Council, Ministry of Health, NMRC/CG/017/2013. Disclosure of Interest None declared

AB0261 Does The Presence of Rheumatoid Factor and/or Anti-Cyclic Citrullinated Peptide Antibody Positivity Affect The Manifestations of Rheumatoid Arthritis?

Background Since the 2010 revision of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria and the availability of anti-cyclic citrullinated peptide antibody (ACCP) testing, patients newly diagnosed with rheumatoid arthritis (RA) are commonly tested for both rheumatoid factor (RF) and ACCP. Patients with ACCP or RF positivity are reported to have worse clinical and radiographic outcomes; however, the presence of ACCP may confound the effects of RF and vice versa. Objectives To determine if there were any differences at study baseline in RA patients who were ACCP-positive, RF-positive, doubly positive and doubly negative in terms of demographics, clinical, functional, laboratory features and radiographic erosions in a multi-ethnic cohort of RA patients in a tertiary rheumatology centre in Singapore. Methods This cross-sectional study was conducted at Tan Tock Seng Hospital in Singapore. 1206 patients fulfilled the ACR 1987 criteria for RA, of whom 475 were excluded due to a lack of both ACCP and RF status. Serum levels of ACCP and RF were analysed for differences in demographics (gender, ethnicity, age, smoking status, disease duration before study entry), clinical activity (Disease Activity Score-28 (DAS-28)), functional status (Health Assessment Questionnaire (HAQ) score), quality of life (Short-Form 36 (SF-36) physical and mental components), haemoglobin levels (Hb), erythrocyte sedimentation rate (ESR), hand radiographic erosions, and the use of prednisolone and disease modifying anti-rheumatic drugs (DMARDs) at study entry. Results 731 patients were studied of whom 491 were ACCP+RF+, 54 were ACCP+, 82 were RF+ and 104 were doubly negative. Mean disease duration of RA prior to study entry was similar among the groups at 97.8–105.1 months (p=0.971) and mean disease duration before first DMARD was 38.8–42.7 months (p=0.966). 24.4% of the ACCP+RF+ patients were in remission (DAS-28 <2.6) compared to 36.6–39.4% in the other groups (p<0.05). ESR was higher (40.4mm/hour) in the ACCP+RF+ group compared to 30.6–30.9 mm/hour in the others (p<0.05). The use of prednisolone and number of DMARDs was higher in the ACCP+RF+ group (1.40±0.71) compared to the doubly negative group (1.13±0.59) (p<0.05). There were no differences in demographics, radiographic erosions, functional status and quality of life scores. Conclusions Patients who had dual positivity for ACCP and RF had lower remission rates and required more corticosteroid and DMARD treatment at baseline. However, this did not seem to have an impact on their functional status, quality of life and radiographic erosions. Future prospective studies would be useful to determine if the prognosis of patients with RA are affected by ACCP and RF positivity. References Hecht C, Englbrecht M, Rech J, et al. Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA; Ann Rheum Dis 2015; 74:2151–2156 Kroot EJ, de Jong BA, van Leeuwen MA, et al. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Res Ther 2005;7:R949–958 Disclosure of Interest None declared

SAT0060 Orthopaedic Surgery in an Asian Rheumatoid Arthritis Cohort: Predictors and Impact on Quality of Life

Objectives To identify predictors of orthopaedic surgery and its impact on quality of life in a South-East Asian rheumatoid arthritis registry cohort. Methods Data was collected from patients enrolled in the Tan Tock Seng Hospital Rheumatoid Arthritis Registry. All patients fulfilled the 1987 ACR criteria for RA. The clinical, extraarticular features (EAF), disease activity score (DAS 28), functional status (Health Assessment Questionnaire, HAQ) and health- related quality of life measures (SF-36) were prospectively collected since 2001. Comparison between those with and without orthopaedic surgical procedures (groups I and II respectively) at entry to the registry till 2013 or death was done. Risk factors for surgery at study entry were determined using logistic regression (STATA SE 10), adjusted for age and disease duration. Results The study comprised of 1049 patients, predominately Chinese (77.9%); 190 patients (18.1%) had surgery (synovectomy 6.4%, arthroplasty 17.5%, arthodesis 1.1%). The mean age of groups I and II were similar (49.2 vs 48.2 years, p=0.35), mean duration from onset of RA to 1st joint surgery was 136.2 months. Group I had significantly longer symptoms before seeking rheumatologists (mean 63.5 vs 32.0 months, p<0.0001), duration from onset of RA to 1st disease modifying drug (74.2 vs 39.3 months, P<0.0001) and disease duration (243.1 vs 151.6 months, p<0.0001). Higher deformed joint count (mean 4.8 vs 1.7, OR 1.13, p<0.001), presence of radiographic erosions (70.4 vs 52.3%, OR 1.46, p<0.05), EAF (36.3 vs 24.1%, OR 1.67, p=0.004), HAQ score >1.5 (15.4 vs 7.5%, OR 3.08, p<0.001 and not DAS 28 or RF positivity were predictive of orthopaedic surgery. Lower scores were seen for the physical functioning domains of the SF36 in the group that had orthopaedic surgery, but there was no significant difference in the mental component between the two groups. Conclusions Delayed diagnosis and delay in initiation of disease modifying therapy were positive predictors of orthopaedic surgery in our cohort of RA patients, independent of disease activity scores and rheumatoid factor positivity. RA patients in this cohort who required orthopaedic intervention report significantly poorer scores on physical quality of life measures. Acknowledgements This study is supported by the Centre Grant, National Medical Research Council, Ministry of Health, Singapore. (CG12Aug17) Disclosure of Interest None declared

THU0143 Heterogeneity of Joint Deformity in Rheumatoid Arthritis Revealed by Cluster Analysis

Background The application of statistical clustering methods to various clinical datasets has revealed unexpected patterns of disease that may have practical implications. There are advantages to categorising patients with rheumatoid arthritis (RA) into distinct subsets for treatment and prognostication. Objectives To examine the cluster pattern of joint deformity of an inception cohort of RA patients. Methods All patients fulfilled the 1987 ACR criteria for RA, had ≤2 years disease duration at recruitment and were followed up from enrolment till 2014. Correlation of joint deformity symptoms at last study visit among the eight joints were analysed using eigen vectors from principal component analysis. K-means clustering analysis was applied to classify the RA patient subgroups based on distribution of joint deformity involvement. Joint deformity pattern was analysed at the last visit and correlated with socioeconomic, extra-articular features (EAF), DAS28 and HAQ scores, rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA) status and treatment. Results The mean age of the RA cohort was 50.4 years, 75.5% were Chinese and mean follow-up period was 88.4 months. Correlation analysis showed that the joint deformity involvement could be classified into three categories: proximal interphalangeal/metacarpophalangeal joint (PIP/MCP), shoulder/elbow/ankle (S/E/A) and wrist/knee/metatasophalangeal (W/K/MTP). Cluster analysis showed four patterns of joint deformity: mild involvement of PIP/MCP joints (group I), dominant involvement of S/E/A and W/K/MTP (group II), W/K/MTP involvement (group III) and dominant PIP/MCP/S/E/A/W/K/MTP involvement (group IV). There was no significant difference in mean age, disease duration, work status, occupation, smoking status, prevalence of RF and ACPA, DAS28 and HAQ scores among the four groups. Group IV patients had a significantly longer symptom duration prior to diagnosis, received higher number of non-biologic DMARDs and were more likely to have radiographic erosions (p<0.05). Unlike other joints, wrist deformity was significantly correlated with prior wrist tenderness or swelling (34.5% of patients). Conclusions Cluster analysis showed four subgroups of RA patients based on pattern of joint deformity. The presence of wrist synovitis at baseline may predict wrist deformity. Factors other than socioeconomic, RF, ACPA need to be explored to explain the clustering of joint deformity in our inception cohort. Acknowledgements We thank Ms Safiyya Mohamed Ali for her kind assistance. Disclosure of Interest None declared