K.L. Chan

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 ≥4u2009American 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.

Functioning and health-related quality of life in Chinese patients with systemic sclerosis: a case–control study

The objective of the study was to study the functioning and health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc) and its associated factors. Consecutive SSc patients and an equal number of age- and gender-matched healthy controls were recruited for the assessment of functioning and HRQoL by the Health assessment questionnaire disability index (HAQ-DI) and Medical Outcomes Study Short Form 36 (SF-36), respectively. The extent of skin involvement of SSc was assessed by the modified Rodnan skin score (mRSS), and disease severity was assessed by the Medsger severity index. Factors associated with functioning and HRQoL in SSc patients were studied by linear regression. Seventy-eight Chinese SSc patients were studied (87xa0% women; age 50.2u2009±u200912.1xa0years; disease duration 7.8u2009±u20096.5xa0years; 81xa0% limited cutaneous subtype). The median mRSS of the patients was 8 (IQR 0–10). Patients with SSc had significantly higher HAQ-DI (0.69u2009±u20090.69 vs 0.04u2009±u20090.18; pu2009<u20090.001) but lower SF36 scores (pu2009<u20090.05 in all domains) than matched controls. Linear regression revealed that the mRSS was inversely associated with the physical component (betau2009=u2009−0.39; pu2009=u20090.001) and mental component scores (betau2009=u2009−0.27; pu2009=u20090.031) of the SF36 but positively correlated with the HAQ-DI score (betau2009=u20090.51; pu2009<u20090.001) adjusted for age, sex, and disease duration. The SF36 and HAQ-DI scores also correlated significantly with the Medsger SSc severity index in the general, peripheral vascular, skin, tendon/joint, and heart domains. SSc patients had impaired physical and social functioning and poorer HRQoL than healthy individuals. The extent of skin involvement, tendon/joint contracture, damage in the heart, and peripheral vascular system were associated with poorer functioning and HRQoL.

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 (≥0.6u2009mg/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.

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±0.53u2009vs 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.

FRI0305 Factors Determining Hydroxychloroquine Serum Levels in A Cohort of Chinese Patients with Systemic Lupus Erythematosus

Objectives To study the factors determining the hydroxychloroquine (HCQ) serum concentration in a cohort of Chinese patients with systemic lupus erythematosus (SLE). Methods Consecutive patients who fulfilled ≥4 of the 1997 ACR criteria for SLE and had received HCQ for 6 months or more were recruited from our lupus clinic and hospital admissions in a 9-month period starting from November 2011. Patients were prescribed HCQ at fixed daily dosages of 400 mg, 300 mg, 200mg or less than 200mg (eg. 200mg 3 or 5 times per week) at the discretion of their attending doctors according to disease activity, organ manifestations and risk factors for HCQ toxicities. Blood was assayed for the serum levels of HCQ by an in-house technique using the tandem mass spectrometry (SPE-MS/MS). Factors affecting HCQ serum concentrations were studied by univariate and multivariate linear regression analyses. Covariates being tested in the regression models included age, sex, body mass index (BMI), prescribed dosage of HCQ, SLE disease activity score (SLEDAI), ever smoking, estimated glomerular filtration rate (eGFR) and concomitant prednisolone. Results 276 SLE patients were studied (94% women; mean age 41.0±13.8 years; SLE duration 8.7±6.6 years). HCQ was primarily used for the treatment of mucocutaneous or musculoskeletal manifestations, or both, in 73%, 78% and 93% of the patients, respectively. Patients were stratified into 3 groups according to the HCQ levels: (1) Total non-compliance (<10 ng/ml); (2) Sub-therapeutic (10–500 ng/ml); and (3) Therapeutic (≥500 ng/ml). The proportion of patients with HCQ levels of <10, 10–500, ≥500 ng/ml was 11%, 77% and 12%, respectively. Patients with total non-compliance to HCQ were more likely to be in clinical and serological remission when compared to the remaining patients (42% vs 24%; p=0.04). However, no difference in the clinical manifestations could be observed between patients with total non-compliance and other patients. After excluding patients with total non-compliance to HCQ therapy, the mean and median HCQ serum concentration of the remaining 245 patients was 300±87ng/ml and 276ng/ml (interquartile range 167–401), respectively. Univariate linear regression revealed that the prescribed HCQ dosage (beta 0.47; p<0.001) and the SLEDAI score at the time of recruitment (beta 0.16; p=0.02) were the significant factors associated with the HCQ serum concentrations. Multivariate linear regression with all the factors being considered in the model showed that the prescribed HCQ dosage (beta 0.50; p<0.001) and eGFR (beta -0.14; p=0.02) were independent factors associated with HCQ serum levels. Age, sex, BMI, smoking, SLEDAI score and concomitant prednisolone were not significantly associated with the HCQ serum concentrations. Conclusions Non-compliance and sub-therapeutic HCQ serum levels were frequent in our cohort of SLE patients, which was related to the low prescribed dosage for maintenance treatment in those with clinical and serological remission. Patients with lower eGFR or receiving higher doses of HCQ were more likely to achieve higher HCQ serum concentrations. Thus, HCQ level monitoring and dosage adjustment may be helpful in SLE patients with impaired renal function to reduce the risk of toxicities. Disclosure of Interest None declared

SAT0296 Is Hyperuricemia An Independent Risk Factor for Arterial Thrombosis in Systemic Lupus Erythematosus

Objectives To evaluate whether hyperuricemia is independently associated with cardiovascular events in a cross-sectional study of Chinese patients with SLE. Methods Consecutive patients who fulfilled ≥4 ACR criteria for SLE were recruited. Fasting blood was taken for serum urate level, along with other atherosclerosis risk factors that included glucose, total, LDL, HDL cholesterol and triglyceride. Patients were assessed for body mass index (BMI), waist circumference and the presence of the metabolic syndrome (MetS) as defined by the updated joint consensus criteria, using the Asian criteria for central obesity. The 4-variable estimated glomerular filtration rate (eGFR) was also calculated. Patients were stratified according to different serum urate levels: <0.35mmol/L, 0.35–0.48mmol/L, 0.48–0.60mmol/L and >0.60mmol/L. Comparison of the prevalence of vascular risk factors, the MetS and arterial thrombotic events (acute coronary syndrome, stroke, peripheral vascular event) was made among patients with different levels of urate. Cox regression models were established to study whether hyperuricemia was independently associated with arterial events with adjustment of demographic variables, eGFR, vascular risk factors and the antiphospholipid (aPL) antibodies. Results 485 SLE patients were studied (93% women; mean age 46.2±14 years); 259 (53%) had renal involvement and 73 (15%) had chronic kidney disease (stage ≥3). Hyperuricemia (urate >0.35mmol/L) was present in 185 (38%) patients. The number of patients who had serum urate levels of 0.35–0.48, 0.48–0.60 and >0.60mmmol/L was 131 (27%), 40 (8.7%) and 14 (2.9%), respectively. Patients with hyperuricemia, compared with those without, were more likely to be men (14% vs 3%; p<0.001), have renal disease (72% vs 42%; p<0.001), hypertension (34% vs 15%; p<0.001), lower eGFR (73.4±34 vs 101±27; p<0.001) but longer SLE duration (14.3±8.7 vs 12.2±7.4 years; p=0.006). The LDL-cholesterol level (3.34±1.37 vs 2.89±1.51mmol/L; p=0.001), triglyceride level (1.62±0.77 vs 1.29±0.78mmol/L; p<0.001), BMI (23.2±4.5 vs 22.3±3.8kg/m2; p=0.04) and occurrence of the MetS (22% vs 12%; p=0.007) were significantly higher in patients with hyperuricemia. Over an observation of 12.9±8.0 years, 50 acute arterial events (17 acute coronary syndrome; 24 stroke, 7 peripheral vascular event and 2 retinal artery thrombosis) developed in 47 patients. Acute coronary events were significantly more common in patients with hyperuricemia than those without (7.6% vs 1.0%; p=0.001). Cox regression analysis revealed that HDL<1.0mmol/L (HR 3.44 [1.62–7.27]; p=0.001], lupus anticoagulant (HR 3.84 [1.92–7.65]; p<0.001) and age of SLE onset (1.03 [1.004–1.05] per year; p=0.02) were independently associated with arterial thrombosis. In separate regression models, elevated urate levels (>0.35, >0.48 or >0.60mmol/L) were not significantly associated with arterial events after adjustment for age, sex, eGFR, smoking, LDL-cholesterol, HDL-cholesterol, triglyceride, BMI, diabetes mellitus, hypertension and the apL antibodies. Conclusions In patients with SLE, hyperuricemia was associated with atherosclerotic risk factors, the MetS and acute coronary events. However, in multivariate regression models, hyperuricemia was not an independent risk factor for any arterial events after adjustment for confounding factors. Disclosure of Interest None declared

SAT0019 Effect of Depressive/Anxiety Symptoms on Quality of Life and Work Disability in Patients with Systemic Lupus Erythematosus

Objectives To study the effect of depressive/anxiety symptoms on quality of life and work disability in Chinese patients with systemic lupus erythematosus (SLE). Methods Consecutive patients who fulfilled ≥4 ACR criteria for SLE were recruited. Depressive and anxiety symptoms were assessed by the Hospital Anxiety and Depression (HAD) scale (0-21 points). Health-related quality of life (HRQoL) was assessed by the validated Chinese version of MOS-Short Form (SF)-36 (mental component [MCS] and physical component [PCS]). Disease activity of SLE was assessed by SLEDAI and physicians global assessment (PGA), whereas organ damage since SLE diagnosis was assessed by the ACR/SLICC damage index (SDI). The effect of depressive/anxiety symptoms on HRQoL was studied by linear regression, with adjustment for confounding covariates that included age, sex, disease activity, organ damage and psychosocial factors such as marital status, educational level, employment status and income. Results 367 SLE patients were studied (95% women; age 40.2±12.9 years; disease duration 9.3±7.2 years). 67 (18%) patients had clinically active SLE (SLEDAI ≥5) and 137 (37%) patients had organ damage (SDI ≥1). 50 (14%) patients had HADS-depression score of ≥10 and 70 (19%) of patients had HADS-anxiety score of ≥10. Patients with depressive score of ≥10 had significantly lower PCS (28.8±18.1 vs 60.5±20.3; p<0.001) and MCS (25.2±15.6 vs 61.9±19.1; p<0.001) of the SF36 than those with score <10. Similarly, significant lower PCS (32.3±18.5 vs 61.4±20.1; p<0.001) and MCS (28.2±15.1 vs 63.4±18.6; p<0.001) were noted in those patients with HAD-anxiety score ≥10 compared to those <10. Excluding retirees, housewives, students and those unemployed within 12 months prior to study, 190 patients were evaluated for work disability. Thirty patients (16%) who were working in 12 months prior to this study quitted their job (N=22) or reduced working hours (N=8) at the time of study entry. The mean daily working hours reduced from 6.4±2.5 to 1.2±2.3 in these patients. The commonest self-reported reasons for reducing/quitting work were joint/muscle aches (47%), fatigue (20%), anxiety/depressive symptoms (17%) and skin lesions causing cosmetic problem (7%). Patients with work disability had significantly higher HAD-depression score than those without (6.31±5.51 vs 3.93±3.72; p=0.03). Other parameters such as age, sex, SLE duration, HAD-anxiety score, mean SLEDAI in the preceding 12 months, total SDI damage score and SF36 score were not significantly different between patients with and without work disability. Linear regression analysis revealed that in all the patients studied, both the MCS and PCS of SF36 score was significantly associated with HAD-depression score (Beta -0.75, p<0.001 and Beta -0.64, p<0.001, respectively) after adjustment for age, sex, SLE duration, years of education, religious belief, marital status, employment, poverty (dependence of government financial subsidy), total SDI damage score and mean SLEDAI in the preceding 12 months. Conclusions Depressive and anxiety symptoms were common in SLE patients and were associated with significantly poorer HRQoL. Patients with depressive symptoms were more likely to have their job quitted or working hours reduced. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2636

AB0656 Golimumab versus Pamidronate for the Treatment of Axial Spondyloarthropathy (SPA): A 48-Week Randomized Controlled Trial

Objectives To compare the efficacy of golimumab (GLM) and pamidronate (PAM) in the treatment of SpA. Methods Study design: an open randomized controlled trial Patients and methods: Inclusion criteria: (1) ≥18 years of age; (2) fulfills 2009 ASAS classification criteria for axial SpA; (3) Active spondylitis as defined by a BASDAI score of ≥4 (with spinal pain score ≥4), despite treatment with NSAIDs for ≥3 months. Exclusion criteria: (1) Hepatitis B/C carriers; (2) Major surgery within 8 weeks; (3) Active infection; (4) Pregnancy/lactation; (5) Contraindications to anti-TNF or bisphosphonates. Patients were randomized to receive GLM (50mg subcutaneously monthly) or PAM (60mg intravenously monthly) in a 2:1 ratio on top of existing therapies. Latent tuberculosis was screened and treated in the GLM arm. Assessment for clinical efficacy (BASDAI, BASFI, BASMI, ESR, CRP, ASDAS, VAS pain, global assessment, SF36) was performed at week 0,2,4,8,12,16,20,24,32,40 and 48. MRI of the spine and SIJ was performed at week 0, 24 and 48 and graded by the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system (SIJ score 0-72; spinal score 0-108). The primary efficacy end-point was the proportion of patients who achieved the ASAS20 response at week 48. Intra-group paired data over time were compared by the paired Students t-test whereas inter-group differences were compared by ANCOVA with adjustment for baseline values. Results 30 patients were recruited (83% men; age 33.4±10.9 years; disease duration 4.4±3.4 years) – 20 assigned to GLM and 10 assigned to PAM. Baseline demographic and clinical characteristics were not significant different between the two arms, except for a non-significantly higher mean ASDAS (CRP) (4.07±0.77 vs 3.70±0.65) and SIJ SPARCC (15.8±17.7 vs 7.8±5.93) score in GLM-treated patients. At week 48, a higher proportion of patients achieved ASAS20 (50% vs 20%; p=0.23) and ASAS40 (35% vs 0%; p=0.04) responses in the GLM compared to the PAM group. The ASDAS, BASDAI, BASFI, CRP and ESR levels significantly improved with GLM treatment but not with PAM. Interestingly, patient reported outcomes such as pain score and SF36 improved significantly in both treatment groups. In patients treated with GLM, the SPARCC SIJ (15.8±17.7 to 3.80±5.19; p<0.01) and spine (11.4±10.8 to 3.56±5.65; p<0.01) scores at week 48 decreased significantly compared to baseline. However, there was only a modest but non-significant reduction in the corresponding MRI scores observed in PAM-treated patients. There was no serious adverse events (SAEs) reported and the frequency of any adverse events (AEs) was not significantly different between the two arms. Minor upper respiratory infection (URI) was the commonest AE (30%), followed by dyspepsia (10%) and deranged liver function (10%) in GLM-treated patients. In patients treated with PAM, the commonest AE was post-infusion fever/myalgia/headache (30%), followed by dyspepsia (10%), phlebitis (10%) and minor URI symptoms (10%). Conclusions In patients with axial SpA, GLM was more effective than PAM in reducing clinical disease activity as well as inflammation of the spine and SIJ. PAM led to improvement in subjective pain and quality of life but did not have significant positive effects on MRI inflammation, CRP or ESR. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3192