S.M. Tse

Hydroxychloroquine Serum Concentrations and Flares of Systemic Lupus Erythematosus: A Longitudinal Cohort Analysis.

To study the relationship between serum hydroxychloroquine (HCQ) concentrations and flares of systemic lupus erythematosus (SLE) in a longitudinal cohort of patients.

Prevalence of remission and its effect on damage and quality of life in Chinese patients with systemic lupus erythematosus

Objectives To study the prevalence of remission and its effect on damage and quality of life (QOL) in Chinese patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled ≥4 American College of Rheumatology criteria for SLE were identified. Their remission status at last clinic visits was determined by the European consensus criteria (complete/clinical remission ± immunosuppressive drugs). The increase in SLE damage index (SDI) in the preceding 5 years was compared between patients who were and were not in remission for ≥5 years. QOL of patients as assessed by the validated Chinese version of the Medical Outcomes Study Short-Form-36 (SF36) and the LupusPRO was also compared between the remission and non-remission groups by statistical analysis. Results 769 SLE patients were studied (92% women; age: 46.4±14.6 years; SLE duration: 12.6±8.1 years). At last visit, clinical remission was present in 259 (33.7%) patients and complete remission was present in 280 (36.4%) patients. Clinical and complete remissions for ≥5 years were achieved in 64 (8.3%) and 129 (16.8%) of the patients, respectively. Patients remitted for ≥5 years were older, and had significantly lower prevalence of renal involvement, leucopenia or thrombocytopaenia. Fifty-three (6.9%) patients in remission ≥5 years were taken off all medications, including hydroxychloroquine (HCQ) (drug-free). Patients who remitted for ≥5 years but off-therapy (except HCQ) had significantly less SDI increment than those who did not remit (0.17±0.53 vs 0.67±1.10; p<0.001). Among 453 patients who had QOL assessment, remission for ≥5 years was associated with significantly higher SF36 and the total health-related scores of the LupusPRO. Conclusions Durable remission can be achieved in a quarter of patients with SLE. Patients with remission for ≥5 years have significantly less damage accrual and better QOL. Prolonged remission is an appropriate criterion for outcome assessment in SLE.

Effect of immunosuppressive therapies on survival of systemic lupus erythematosus: a propensity score analysis of a longitudinal cohort:

Objectives The aim of this study was to study the relationship between immunosuppressive drug treatment and survival in patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled four or more American College of Rheumatology criteria for SLE were followed longitudinally. Clinical characteristics, use of immunosuppressive agents and mortality were reviewed. Cox regression was used to study the relationship between immunosuppressive treatment and survival, adjusted for age, sex, vascular risk factors, organ damage, the anti-phospholipid antibodies and a propensity score for the indication of individual immunosuppressive agent derived from separate regression models. Results A total of 803 SLE patients were studied (92% women; age of SLE onset 33.2±14 years; follow-up time 10.8±7.7 years). The frequencies of ever use of immunosuppressive agents were: high-dose prednisolone (≥0.6 mg/kg/day for ≥4 weeks) (85%), azathioprine (63%), cyclophosphamide (25%), mycophenolate mofetil (27%), the calcineurin inhibitors (23%) and hydroxychloroquine (69%). Ninety-seven patients (12%) died and 56 (7%) patients were lost to follow-up. The causes of death were infection (44%), cerebrovascular events (12%), cardiovascular events (10%) and malignancy (8.2%). Cox regression revealed that the ever use of high-dose prednisolone, mycophenolate mofetil, calcineurin inhibitors or cyclophosphamide was not significantly associated with improved survival. However, the ever use of hydroxychloroquine (hazard ratio 0.59 (0.37–0.93); P=0.02) and azathioprine (hazard ratio 0.46 (0.28–0.75); P=0.002) was significantly associated with reduced mortality (41% and 54%, respectively) after adjustment for the propensity score and other confounding factors. A similar beneficial effect of hydroxychloroquine and azathioprine on survival was also observed in patients with lupus nephritis. Conclusions In this longitudinal cohort of Chinese SLE patients, the ever use of hydroxychloroquine and azathioprine was significantly associated with a probability of better survival. Treatment with high-dose prednisolone, cyclophosphamide, mycophenolate mofetil or the calcineurin inhibitors was not associated with long-term survival benefit.

183 Effect of the metabolic syndrome on organ damage and mortality in chinese patients with systemic lupus erythematosus: a longitudinal analysis

Background and aims To study the effect of the metabolic syndrome(MetS) on organ damage and mortality in patients with SLE. Methods Consecutive patients who fulfilled ≥4 ACR criteria for SLE were assessed for the presence of the MetS in 2010. The MetS was defined by the updated joint consensus criteria, using the Asian criteria for central obesity. Longitudinal data on organ damage, vascular events and mortality were retrieved from our database. The association of the MetS with new organ damage and mortality was studied by logistic regression. Results 577 SLE patients were studied (93% women; age41.2±13.4 years; SLE duration9.3±7.2 years). The mean follow-up time of the patients was 66.3±1.8 months. 85 (14.7%) patients qualified the MetS. New organ damage and vascular events developed in 128 (22%) and 23 (4.0%) patients, respectively. Thirty-nine (6.8%) patients died. Patients with MetS, compared to those without, had significantly higher SDI accrual at their last visits (0.70±1.0 vs 0.26±0.6;p<0.001). New vascular events (11% vs 2.8%; p=0.001), all-cause mortality (14% vs 5.5%; p=0.003), death due to vascular complications (7.1% vs 0.2%;p<0.001) were significantly more common in patients with MetS than those without. Logistic regression revealed that the MetS was significantly associated with new damage in the ocular, renal, cardiovascular and endocrine system, adjusted for age, sex, SLE duration and the antiphospholipid antibodies.The presence of the MetS showed a significant increase in vascular mortality after adjustment for the same covariates (OR 30.3 [3.42–268]; p=0.002). Conclusions The MetS is significantly associated with new organ damage, vascular events and mortality in patients with SLE.

449 Effect of disease remission on organ damage and quality of life in chinese patients with systemic lupus erythematosus

Background and aims To study the effect of disease remission on organ damage and quality of life(QOL) in Chinese patients with SLE. Methods Adult patients who fulfilled the ACR criteria for SLE were identified and their remission status at last visits was determined by the European consensus criteria (complete/clinical remission ± immunosuppressive drugs). The increase in SLE damage index (SDI) in the preceding 5 years was compared between patients who were and were not in remission for ≥5 years. QOL of patients as assessed by the validated Chinese version of the SF36 and the LupusPRO. Results 769 SLE patients were studied (92%women; age46.4±14.6 years, SLE duration 12.6±8.1 years). Clinical remission (serologically active) was present in 259 (33.7%) patients (median 43 months) and complete remission (clinically and serologically inactive) was present in 280 (36.4%) patients (median 51 months). Clinical and complete remission for ≥5 years was achieved in 64 (8.3%) and 129 (16.8%) of the patients, respectively. 53 (6.9%) patients in remission ≥5 years were taken off all medications including HCQ. Patients remitted for ≥5 years were older, and had significantly lower prevalence of renal and haematological disease. Moreover, these patients had significantly less SDI increment than those who did not remit (0.17±0.53 vs 0.67±1.10;p<0.001). Among 453 patients who had QOL assessment within 6 months of last visits, remission for ≥5 years was associated with significantly better SF36 and the health-related scores of the LupusPRO. Conclusions Durable drug-free remission in SLE is uncommon. Patients with complete or clinical remission for ≥5 years have significantly less damage accrual and better QOL.

SAT0266 Effect of the metabolic syndrome on organ damage and mortality in chinese patients with systemic lupus erythematosus: a longitudinal analysis

Objectives To study the effect of the metabolic syndrome (MetS) on organ damage and mortality in patients with SLE. Methods Consecutive patients who fulfilled ≥4 ACR criteria for SLE and were assessed for the presence of the MetS between 2010 and 2011 were included. Those patients who did not have MetS assessment or succumbed before 2010 were excluded. The MetS was defined by the updated joint consensus criteria, using the Asian criteria for central obesity, when ≥3 of the following components were present: (1) Increased waist circumference to ≥90cm in men or ≥80cm in women; (2) Elevated blood pressure to ≥130/85mmHg or requiring drug therapy; (3) Elevated serum triglyceride level to ≥1.7mmol/L; (4) Reduced serum high density lipoprotein (HDL)-cholesterol to ≤1.0mmol/L in men and ≤1.3mmol/L in women; and (5) Elevated fasting glucose level to ≥5.6mmol/L. Longitudinal data regarding new organ damage, vascular events and mortality on follow-up were retrieved from our cohort database. The association of the MetS with new organ damage and mortality was studied by logistic regression analyses. Results 577 SLE patients were studied (93% women; age at entry 41.2±13.4 years; SLE duration 9.3±7.2 years). The mean follow-up time of the patients since entry was 66.3±1.8 months. The mean body mass index (BMI) of the patients was 22.3±3.9kg/m2 (11% >27kg/m2). A total of 85 (14.7%) patients qualified the MetS (28% fulfilling waist; 20% fulfilling blood pressure; 25% fulfilling triglyceride; 33% fulfilling HDL and 9.2% fulfilling glucose criteria). New organ damage and vascular (coronary, cerebrovascular and peripheral vascular) events developed in 128 (22%) and 23 (4.0%) patients, respectively. The most common new arterial events were stroke (50%), acute coronary syndrome (33%) and peripheral vascular disease (17%). Thirty-nine (6.8%) patients died (infection 36%; vascular causes 18%; cancer 15%; lung fibrosis 8%; suicide 3%). Patients with the MetS (N=85), when compared to those without (N=492), had significantly higher SDI accrual at their last clinic visits (0.70±1.0 vs 0.26±0.6; p<0.001). Regarding individual systems, the increase in SDI scores in the ocular, renal, cardiovascular, musculoskeletal and endocrine (new diabetes mellitus) systems were significantly higher in the MetS group of patients. New vascular events (11% vs 2.8%; p=0.001), all-cause mortality (14% vs 5.5%; p=0.003), death due to vascular complications (7.1% vs 0.2%; p<0.001) were significantly more common in patients with MetS than those without. Logistic regression revealed that the MetS was significantly associated with new damage in the ocular (OR 2.77 [1.05–7.34]; p=0.04, renal (OR 4.72 [1.86–12.0]; p=0.001), cardiovascular (OR 3.66 [1.03–12.9]; p=0.04] and endocrine system (OR 41.9 [4.93–357]; p=0.001), adjusted for age, sex, SLE duration and the antiphospholipid antibodies (IgG-anticardiolipin or the lupus anticoagulant). The presence of the MetS increased the risk of new vascular events (OR 2.94 [1.18–7.31]; p=0.02), all-cause mortality (OR 1.60 [0.73–3.47]; p=0.24) and vascular mortality (OR 30.3 [3.42–268]; p=0.002) after adjustment for the same covariates. Conclusions In this 5-year longitudinal study, the MetS is significantly associated with new organ damage, vascular events and mortality in patients with SLE. Disclosure of Interest None declared

FRI0393 Standardized Incidence Ratio (SIR), time Trend and Risk Factors of Avascular Bone Necrosis (AVN) in Patients with Systemic Lupus Erythematosus (SLE)

Objectives To study the standardized incidence ratio (SIR), time trend and risk factors of AVN in patients with SLE. Methods The records of all patients who fulfilled ≥4 ACR criteria for SLE in our unit between 1999 and 2014 were reviewed. Patients who developed AVN at any sites ever since the diagnosis of SLE were identified. A group of SLE controls who did not have evidence of AVN were randomly selected from our cohort database in a 4:1 (control/case) ratio, matched for age, sex and SLE duration. The SIR of AVN in SLE and its time trend was calculated by data retrieved from our hospital clinical information registry and the Census data from our Government. Risk factors for AVN in SLE were studied by multivariate logistic regression. The following factors were considered to be covariates in the regression model: hypertension, diabetes mellitus, lipid level, previous septic arthritis, maximum daily dose and cumulative dose of prednisolone ever used, cushingoid body habitus, cutaneous vasculitis, Raynauds phenomenon, antiphospholipid antibodies, and a propensity score derived from a separate logistic regression model for the probability of use of high-dose prednisolone (>0.8mg/kg/day) for different SLE manifestations. Results 55 patients with symptomatic AVN (87%women;age 33.4±12.4 years; SLE duration 61.2±62.2 months) and 220 matched SLE controls (87% women, age 34.3±10.6 years; SLE duration 71.7±50.1 months) were studied. The point prevalence of AVN in our SLE cohort (N=743) was 7.4%. All the patients with AVN had been treated with glucocorticoids (GCs). Compared to controls, AVN patients had used a significantly higher cumulative doses of prednisolone (16.5±14.6 vs 10.7±11.3 grams; p=0.003). A total of 104 sites of AVN were diagnosed in 55 patients (69%≥2 sites). The hip was most commonly affected (82%), followed by the femoral condyle (9%) and the humeral head (5%). Bilateral involvement was present in 67% of the patients. Surgical treatment (core decompression, vascularized bone graft or joint replacement) was performed for 41% of the AVN lesions. The age and sex stratified SIRs of AVN in our SLE patients was 131 (86.6-199; p<0.001) in the period 1995-2004 and 56.0 (34.3-91.4; p<0.001) in the period 2005-2014. In both decades, the age stratified SIR was highest in the youngest age group (<19 years of age) with figures of 1161 (357-3770; p<0.001) in 1995-2004 and 778 (267-2270; p<0.001) in 2005-2014, respectively. Logistic regression analysis revealed the following factors independently associated with the occurrence of AVN, adjusted by the propensity score for high-dose prednisolone: preceding septic arthritis of the involved joint (odds ratio [OR] 15.4[1.3-181.2]; p=0.03), Cushingoid body habitus (OR 2.3[1.0-5.1]; p=0.043), LDL-cholesterol (OR 1.4[1.0-2.0]; p=0.041), maximum daily dose of prednisolone (mg/kg) (OR 6.0[1.2-30.7]; p=0.031) and cumulative dose of prednisolone in the first 6 months of treatment of a SLE flare (OR 1.4[1.0-1.8]; p=0.047). Conclusions AVN is prevalent in SLE patients, particularly in younger patients. GC use, Cushingoid body habitus, serum LDL-cholesterol level and previous septic arthritis are independently associated with AVN. There is a trend of reduction in the SIR of AVN in our SLE patients over the past 2 decades, which is probably attributed by the judicious use of GCs and the early administration of GC-sparing agents. Disclosure of Interest None declared

THU0308 Use of Complementary and Alternative Medicine (CAM) in Chinese Patients with Rheumatic Diseases: Prevalence and Associated Demographic, Clinical and Social Factors

Objectives To study the frequency of use of complementary and alternative medicine (CAM) in Chinese patients with rheumatic diseases and the associated demographic, clinical and social factors. Methods A cross-sectional questionnaire study on the use of CAM was carried out in patients who attended the rheumatology clinics of Tuen Mun and Pok Oi Hospital between June and December 2014. Inclusion criteria: adult patients (≥18 years) with chronic autoimmune rheumatic diseases. Exclusion criteria: illiterate or mentally incapable. Basic demographic, psychosocial factors and clinical information were obtained by questionnaire completion and medical record review. The self-perceived control of the underlying disease process was assessed on a visual analog scale (0-100), with higher score being a more sense of disease remission. Missing information was clarified with phone contact of the participants by our research assistants. A multivariate logistic regression model was established to study the factors associated with the use of CAM. Results 1335 patients were studied (75% women, age 48.4±13 years). The underlying rheumatic diseases were: rheumatoid arthritis (RA) (N=642), systemic lupus erythematosus (SLE) (N=347), spondyloarthritis (SpA) (N=142), psoriatic arthritis (PSA) (N=91), systemic sclerosis (SSc) (N=39), inflammatory myopathies (N=14), systemic vasculitides (N=10) and miscellaneous rheumatic disorders (N=50). The mean disease duration was 9.7±8.4 years and the mean years of education in the participants was 10.4±2.9 years. 473 (35%) patients were single/divorced/widowed and 142 (11%) patients were receiving government subsidy for living (poverty). 400 (30%) patients had religious belief: Buddhism (46%), Christianity (43%). The self-perceived score of disease control was 64.8±23. CAM was ever used in 705 (53%) patients and the most common forms of CAM were: traditional Chinese medicine (TCM)(59%), acupuncture (44%), massage (24%), cupping (17%) and omega-3 fatty acid (15%). The proportions of patients with different underlying diseases who had ever used CAM were: SpA (64%), PSA (60%), SSc (59%), RA (54%), SLE (44%), systemic vasculitides (40%). Only 41% of these patients had informed medical staff about the use of CAM and 4% patients had altered the dosage of western medicine without advice from their attending rheumatologists. 505 (72%) patients found CAM somehow effective in alleviating their symptoms. Logistic regression analysis showed that the use of CAM was associated with the presence of religious belief (odds ratio [OR] 1.29 [1.00-1.67]; p=0.047), years of education (OR 1.08 [1.02-1.13]; p=0.005), disease duration (per year) (OR 1.02 [1.006-1.04]; p=0.005) and self-perceived score for disease control (per point) (OR 0.992 [0.99-0.997]; p=0.003). Age, sex, family income and marital status were not associated with the use of CAM. Conclusions The use of CAM is common in Chinese patients with rheumatic diseases, and may affect treatment adherence or aggravate the toxicities of existing therapies. Associated factors for CAM use are inflammatory arthritis, longer disease duration, higher educational background and a lower sense of perceived disease control. Better communication on the use of CAM should be made to our patients, particularly those who are more likely to adopt these measures. Disclosure of Interest None declared

OP0264 Factors Associated with Renal Remission, Relapse and Long-Term Renal Function Decline in Lupus Nephritis Treated with Combined Prednisolone and Mycophenolate Mofetil (MMF) or Tacrolimus (TAC)

Objectives To study the factors associated with renal remission, relapse and renal function decline in patients with lupus nephritis treated initially with combined steroid and MMF or Tac. Methods Data were extracted from a RCT of the efficacy of MMF vs Tac for induction treatment of lupus nephritis. All recruited patients were treated with high-dose prednisolone with either MMF (2-3g/day) or Tac (0.1-0.06mg/kg/day) for 6 months. Patients with good clinical response were shifted to azathioprine (AZA) for maintenance. Rescue therapies were given to patients who did not respond to induction therapy. Factors associated with complete renal response (CR), relapse and renal function decline at 5 years were studied by regression analyses. Results 150 patients (92% women) with active lupus nephritis were studied (ISN/RPS class III±V 36%; IVG/S±V 46; pure V 19%; age 35.5±12.8 years). 102 (68%) patients had first-time nephritis. The mean histological activity and chronicity score was 8.2±3.4 and 2.6±1.6, respectively. At baseline, 59 (39%) patients were hypertensive and 67% patients had CrCl<90ml/min. At 6 months, 61% patients achieved CR, 24% had partial response (PR) but 15% patients had no response (NR). Logistic regression revealed that the baseline urine P/Cr ratio (OR 0.75 [0.57-0.99]; p=0.04) and the presence of histological membranous feature (OR 0.25 [0.07-0.91]; p=0.04) were independently associated with CR at 6m. Treatment regimen (MMF or Tac), age, sex, histological activity or chronicity score, positive anti-dsDNA, depressed C3 level, and other baseline renal parameters were not significantly associated with renal response at 6m. AZA maintenance was given to 59 (78%) MMF-treated (dose 82.5±24 mg/day) and 60 (81%) TAC-treated patients (dose 86.5±21 mg/day; p=0.32). Patients with NR were re-induced with CYC (N=20), low-dose combination of MMF and TAC (N=5), cross-over to TAC (N=4) or cross-over to MMF (N=2). After a follow-up of 60.8±26 months, proteinuric and nephritic renal flares occurred in 24% and 18% of patients treated initially with MMF and 35% and 27% in those treated with TAC, respectively. In patients who achieved CR or PR after initial treatment, Cox regression showed that the female sex (HR 10.9 [1.19-101]; p=0.04), positive anti-dsDNA at month 6 (HR 4.95 [1.64-14.9]; p=0.005) and the use of ACE inhibitor after 6 month (HR 8.86 [1.28-61.2]; p=0.03) were independently associated with renal flares (proteinuric or nephritic). The cumulative incidence of a composite outcome of decline of CrCl by ≥30%, development of CKD stage 4/5 or death at 5 years was 21% in patients treated with MMF and 22% in those treated with TAC. Factors significantly associated with this outcome were first-time nephritis (HR 0.21 [0.05-0.82]; p=0.03), creatinine clearance (CrCl) at 6 month (HR 0.97 [0.95-0.99]; p=0.005) and the use of AZA maintenance (HR 0.23 [0.49-4.30]; p=0.046). Conclusions Tac is non-inferior to MMF for induction therapy of lupus nephritis. More proteinuria at baseline and the presence of histological membranous features are unfavorably associated with renal response at 6 months. Female patients and persistent elevation of anti-dsDNA after induction therapy are associated with renal flares. Lower CrCl at 6 months and the absence of AZA maintenance are associated with renal function deterioration after 5 years. Disclosure of Interest None declared

AB0558 Association of the Metabolic Syndrome (Mets) with Vascular Complications, End Stage Renal Failure (ESRF) and Mortality in Patients with Systemic Lupus Erythematosus (SLE): A Cohort Analysis

Objectives To study the association between the metabolic syndrome (MetS) and vascular events, end stage renal failure (ESRF) and mortality in patients with SLE Methods Patients who fulfilled ≥4 1997 ACR criteria for SLE and were followed in the rheumatology clinics of Tuen Mun Hospital, Hong Kong were studied. Inclusion criteria were those who had clinical and laboratory assessment for the presence of the MetS within 5 years of the latest date of follow-up or death. The MetS was defined by the updated joint consensus criteria, using the Asian criteria for central obesity, when ≥3 of the following components were present: (1) Increased waist circumference to ≥90cm in men or ≥80cm in women; (2) Elevated blood pressure to ≥130/85mmHg or requiring drug therapy; (3) Elevated serum triglyceride level to ≥1.7mmol/L; (4) Reduced serum high density lipoprotein (HDL)-cholesterol to ≤1.0mmol/L in men and ≤1.3mmol/L in women; and (5) Elevated fasting glucose level to ≥5.6mmol/L. Data on vascular complications (cerebrovascular, cardiovascular, peripheral vascular disease) and the occurrence of ESRF were retrieved from our cohort database. The association of the MetS with various vascular events, ESRF and mortality was studied by logistic regression models with adjustment for age, sex and the follow-up time since the onset of SLE. Results 660 SLE patients were studied (93% women; age 45.4±14 years). The mean follow-up time of the patients since the onset of SLE was 12.2±7.8 years. 143 SLE patients were excluded (younger age and shorter disease duration; but no difference in the frequency of SLE manifestations compared with the included patients). The mean body mass index (BMI) of the patients studied was 22.4±4.0kg/m2 (13% >27kg/m2). 97 (15%) of the studied patients qualified the MetS (28% fulfilling waist; 19% fulfilling blood pressure; 27% fulfilling triglyceride; 32% fulfilling HDL and 10% fulfilling glucose criteria). There were a total of 88 arterial vascular events in 77 (11.7%) patients. The most common arterial events were stroke/transient ischemic attack (57%), followed by acute coronary syndrome/angina (27%), peripheral vascular disease (PVD) (12.5%) and arterial thrombosis at other sites (4.5%). 24 (3.6%) patients in our SLE cohort developed ESRF. Separate logistic regression models revealed that the MetS was associated with any arterial events (odds ratio [OR] 2.84 [1.62-5.00]; p<0.001), coronary events (OR 3.41 [1.40-8.30]; p=0.007; PVD and other arterial events (OR 6.09 [1.84-20.1]; p=0.003), adjusted for age, sex and follow-up time. The MetS, however, was not significantly associated with cerebrovascular events (OR 2.00 [0.98-4.06]; p=0.06). The presence of the MetS was associated with mortality (OR 2.27 [1.20-4.28]; p=0.01) and the occurrence of ESRF (OR 5.67 [2.30-14.0]; p<0.001). Conclusions The MetS, which is a constellation of vascular risk factors, was significantly associated with coronary and peripheral arterial events in patients with SLE. Moreover, the presence of the MetS within 5 years of latest follow-up was associated with mortality and the occurrence of ESRF. Disclosure of Interest None declared