Ka Lung Yu

Prevalence of atherosclerotic risk factors and the metabolic syndrome in patients with chronic inflammatory arthritis

To evaluate the prevalence of the metabolic syndrome in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA).

Effect of disease activity and damage on quality of life in patients with systemic lupus erythematosus: a 2‐year prospective study

Objectives: To examine the effect of disease activity and damage on health‐related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). Methods: Consecutive SLE patients and matched controls were recruited for a study of HRQoL using the Medical Outcomes Study Short Form‐36 (SF‐36). SLE activity and damage was assessed by the Safety of Oestrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA‐SLEDAI) and the American College of Rheumatology/Systemic Lupus International Collaborating Clinics (ACR/SLICC) Damage Index (SDI), respectively. Patients were prospectively followed for repeat HRQoL assessment at 2 years. The effects of cumulative disease activity and new damage on changes in SF‐36 scores were evaluated. Results: One hundred and fifty‐five patients were studied (94% women; age 37.8±11.3 years; SLE duration 7.2±5.4 years). Fifty (32%) patients had active disease and 75 (48%) had organ damage at baseline. Compared with age‐ and gender‐matched controls, SLE patients had lower SF‐36 scores, and the difference remained significant after adjustment for income and education level. SF‐36 scores in SLE patients correlated inversely with SDI but not with SELENA‐SLEDAI scores. After 2 years, there was a significant drop in the mental component score of the SF‐36. Regression analysis revealed that new damage was the only determinant for a reduction in SF‐36 scores. Patients with higher cumulative disease activity had a greater drop in bodily pain and general health subscores. Conclusions: Impaired HRQoL is more common in SLE patients than controls, regardless of age, sex, education and poverty. Pre‐existing organ damage is associated with poorer HRQoL and new damage predicts a further decline in HRQoL. Persistent disease activity is associated with deterioration in certain domains of the SF‐36.

Risk and predictors of work disability in Chinese patients with systemic lupus erythematosus

The aim of this study is to determine the risk and predictive factors for work disability in patients with SLE. A cross-sectional questionnaire study was performed to evaluate the employment status of a sample of consecutive Chinese patients with SLE. Demographic, socioeconomic data (age, gender, marital status, years of education and household income), employment status, self-reported fatigue score and disease characteristics (SLE duration, organ damage and disease activity) were collected. Work disability was defined by the failure to work due to SLE. The cumulative incidence of work disability since the time of SLE diagnosis was studied by a Kaplan Meier’s plot, and factors predictive of work disability were studied by Cox regression. A total of 147 patients with SLE were studied (mean age = 39.4 ± 11.3 years; 95% women). Among 105 patients who were working at the time of SLE diagnosis, 39 (37%) lost their ability to work as a result of SLE after a mean disease duration of 10.0 ± 6.1 years. Twenty-two (56%) patients lost their work ability within 2 years of diagnosis of SLE. The self-reported reasons for job loss were musculoskeletal pain (87%), skin disease (26%), renal problem (21%), fatigue (85%), memory deterioration (51%), anxiety or depressive symptoms (74%), too frequent sick leave (10%) and long-term hospitalisation (10%). The cumulative risk of work disability was 36% at 5 years after SLE diagnosis. In a Cox regression model, age (HR = 1.06 [1.02–1.11] per year; P = 0.008), self-reported fatigue score (HR = 1.06 [1.01–1.10] per point; P = 0.01) and mean disease activity score in the preceding two years (HR = 1.20 [1.02–1.42] per point; P = 0.03) were independently associated with working disability. In all, 37% of this group of patients with SLE lost their work ability after having the disease for 10 years. More than 50% of these patients developed work disability within the first 2 years of SLE diagnosis. Older age, fatigue and more active disease were independent predictors of work disability.

Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial

Objectives To study the efficacy of raloxifene in preventing bone mineral density (BMD) loss in women receiving long-term glucocorticoids (GC). The study took the form of a parallel-group randomised double-blinded placebo-controlled trial. Methods Postmenopausal women without hypercoagulability risk factors who were prevalent GC users were randomised to receive either raloxifene (60 mg/day) or placebo (1 tablet/day) on top of calcium (1000 mg/day) and calcitriol (0.25 μg/day). BMD of the hip and spine (primary outcome), bone turnover markers and new vertebral fractures (secondary outcomes) at month 12 were assessed. Results Between December 2006 and December 2008, 114 patients were recruited (age 55.3±7.7 years). The duration and dose of prednisolone received was 62.2±64 months and 6.7±5.9 mg/day, respectively. Baseline vertebral fracture was present in six (5%) patients. In all, 57 patients were allocated to each of the treatment arms. Demographic data, osteoporotic risk factors and BMD at various sites were similar between the two groups of patients. At month 12, a significant gain in the lumbar spine (+1.3±0.4%; p=0.004) and total hip BMD (+1.0±0.4%; p=0.01) was observed in patients treated with raloxifene but a significant decrease in BMD of the lumbar spine (−0.9±0.4%; p=0.045) and hip (−0.8±0.3%; p=0.01) occurred in the placebo group. The femoral neck BMD did not change significantly in favour of raloxifene. Three new fractures developed exclusively in the patients treated with placebo. Bone formation (serum osteocalcin and procollagen type I N-terminal) and resorption (urine deoxypyridinoline and type I collagen) markers decreased significantly in the raloxifene group but not in patients treated with placebo. Leg cramps were numerically more frequent in the raloxifene group (7% vs 0%) but thromboembolism was not reported in any patients. Conclusions In postmenopausal women receiving long-term GCs, raloxifene is well tolerated and significantly increases spinal and hip BMD after 12 months of treatment.

Combined low-dose mycophenolate mofetil and tacrolimus for lupus nephritis with suboptimal response to standard therapy: a 12-month prospective study

Objective The objective of this paper is to evaluate the efficacy of combined mycophenolate mofetil (MMF) and tacrolimus (TAC) for lupus nephritis with suboptimal response to standard therapy. Methods Inclusion criteria for patients: (1) biopsy-confirmed active lupus nephritis; and (2) inadequate response to ≥2 immunosuppressive regimens. While prednisolone (≤10 mg/day) and angiotensin-converting enzyme inhibitors were continued, immunosuppressive agents were replaced by combined MMF (1 g/day) and TAC (4 mg/day). Patients were followed every 2 months for the clinical response and adverse events at 12 months. Results Twenty-one patients were recruited (20 women; age 35.8 ± 9.2 years; systemic lupus erythematosus (SLE) duration 111 ± 51 months). The histological classes of lupus nephritis were: IV/III (33%), V + III/IV (33%) and pure V (33%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4 ± 33 ml/min (<90 ml/min in 57%), 3.27 ± 1.5 and 30.1 ± 5.9 g/l, respectively. Thirteen (62%) patients had active urinary sediments and 17 (81%) patients had active lupus serology. At 12 months, eight (38%) patients had very good response, one (5%) patient had good response and five (24%) patients had partial response. Significant improvement in uP/Cr, albumin, complement C3 and anti-dsDNA titer, and stabilization of CrCl was observed in the responders. Thirty-three adverse events were reported in 18 patients: major infection requiring hospitalization (6%), infection not requiring hospitalization (27%), herpes infection (9%), diarrhea (12%), cramps (9%), dyspepsia (6%), transient increase in serum Cr (6%), alopecia (4%), facial twitching (3%), tremor (3%) and diabetes mellitus (3%). None of these had led to protocol withdrawal. Conclusions Combined low-dose MMF and TAC is an option for lupus nephritis that fails to respond adequately to standard regimens, with two-thirds of patients improving after 12 months. Longer-term observation is needed to confirm its efficacy and safety.

Rituximab for Refractory Rheumatoid Arthritis: A 24-Week Open-Label Prospective Study

Objectives To study the efficacy of rituximab in active rheumatoid arthritis (RA) patients refractory to disease modifying anti-rheumatic drugs (DMARDs) including the tumor necrosis factor (TNF)-α antagonists. Methods Adult patients with active RA despite adequate therapies with conventional DMARDs or anti-TNFα agents for at least 3 months were recruited. Inclusion criteria were: (1) Positive RF / anti-CCP; (2) ≥ 6 swollen joints and ≥ 8 tender joints; (3) ESR ≥ 28 mm/hr or CRP ≥ 10 mg/L. Eligible patients were given intravenous rituximab infusions at a dose of 1000 mg on days 1 and 15. Assessment was performed 4-weekly thereafter and included tender joint counts (TJC), swollen joint counts (SJC), physician’s and patient’s global assessment, patient’s pain assessment (VAS 0-100 mm), disability index (HAQ-DI), quality of life (SF36), fatigue score (FACIT-F), ESR and CRP. The DAS28, EULAR and ACR responses at week 24 were evaluated. Results 10 patients (8 women and 2 men) were studied (mean age: 49 years; mean RA duration 7.4 years). Baseline TJC and SJC were 25.1 ± 13.2 and 12.8 ± 5.4 respectively. The mean DAS28 score was 7.1 ± 0.7, and the mean CRP and ESR levels were 52.3 ± 60 mg/L and 95.8 ± 32 mm/hr, respectively. The median number of failed DMARDs was 4 and two patients had failed anti-TNFα treatment. At week 24, there was a significant drop in TJC, SJC, ESR and CRP. The HAQ-DI score also decreased from 2.1 to 1.7 (p=0.04) while the total SF-36 score improved from 24.8 to 38.3 (p=0.008). Sixty percent of patients achieved EULAR moderate-to-good response. Half of the patients achieved ACR20 and two achieved ACR50 / 70 response. Only one patient experienced a minor infusion reaction. Conclusions Rituximab is effective and well tolerated in patients with refractory RA.

Prevalence of the antiphospholipid syndrome and its effect on survival in 679 Chinese patients with systemic lupus erythematosus: a cohort study.

AbstractIn this work we evaluate the prevalence of the antiphospholipid syndrome (APS) and its impact on survival in Chinese patients with systemic lupus erythematosus (SLE). We studied a prospective cohort of southern Chinese patients who fulfilled ≥4 American College of Rheumatology criteria for SLE. The cumulative rate of survival over time was calculated by the Kaplan-Meier method. APS was defined by the 2006 updated consensus criteria. We evaluated the prevalence and manifestations of APS, and compared the survival of patients with and without APS. We followed 679 patients with SLE (92% women; age of onset, 32.5 ± 14 yr) for 9.7 ± 7.3 years. Sixty-eight (10%) patients died and 33 (4.9%) patients were lost to follow-up. Forty-four (6.5%) patients met the criteria for APS, manifested by the following: ischemic stroke (55%), deep venous thrombosis (32%), obstetric morbidity (14%), cardiovascular events (9%), and peripheral vascular disease (9%). Nine (9/44 [20%]) APS patients died, which was more frequent than the non-APS patients (59/635 [9%]; p = 0.02). The cumulative mortality of patients with APS was 4.6% at 5 years, 7.8% at 10 years, and 22.2% at 15 years, which was not significantly higher than that of non-APS patients (5.4% at 5 years, 9.2% at 10 years, and 11.3% at 15 years; p = 0.14). However, if we considered only patients with APS caused by arterial thrombosis, the presence of APS was significantly associated with mortality (hazard ratio, 2.29; 95% confidence interval, 1.13–4.64; p = 0.02). We conclude that the presence of APS increases the mortality risk of Chinese patients with SLE, which is mainly contributed by arterial thrombotic events.Clinical significance: 1) APS is infrequent in southern Chinese patients with SLE compared to white patients. 2) Arterial thrombosis is a more common manifestation of APS than venous thrombosis in Chinese SLE patients. 3) APS related to arterial thrombosis is associated with increased mortality in Chinese patients with SLE.

SAT0216 Relationship between individual organ damage and mortality of systemic lupus erythematosus (SLE): A prospective cohort study of 679 patients

Objectives To study the relationship between damage in different organ systems and mortality in patients with SLE. Methods 679 patients who fulfilled at least 4 of the ACR criteria for SLE between 1995 and 2011 were prospectively followed. The cumulative rate of survival was studied by Kaplan-Meier’s plot. For those who died during the disease course, data were censored at the time of death. For other patients, including those who were lost follow-up, data were censored at the time of last clinic visits. Organ damage was assessed by the ACR SLICC damage scores (SDI). Cox regression models were established to study the association between damage in individual systems and mortality in this cohort of patients. Results 679 SLE patients were studied (623 women, 92%). All were ethnic Chinese. The mean age of onset of SLE was 32.5±13.6 years and the mean follow-up time of the entire cohort of patients was 117±89 months. 67 (9.9%) patients died during the course of illness and 33 (4.9%) patients were lost to follow-up. 23 (3.4%) patients developed end stage renal failure (ESRF). The main contributing causes of death were: infection (51%), cardiovascular events (12%), cerebrovascular events (16%), cancer (9%), suicide (3%) and others (8%). Infective complications were the commonest causes of death both in patients with disease duration of less (55%) and more than 5 years (47%). In patients with SLE for less than 5 years, 19% of all deaths were caused by vascular events, which was lower than those with disease for more than 5 years (36%). The cumulative survival rate of the patients was 94.8% at 5 years, 91.3% at 10 years and 88% at 15 years. 301 (44%) patients had organ damage (SDI score ≥1). Among patients who had organ damage, the frequency of damage in individual systems was, in decreasing order: neuropsychiatric (N=102, 15%), musculoskeletal (N=93, 14%), renal (N=78, 11%), ocular (N=46, 6.8%), cardiovascular (N=38, 5.6%), pulmonary (N=36, 5.3%), gonadal (N=32, 4.7%), endocrine (N=23, 3.4%), peripheral vascular (N=22, 3.2%), malignancy (N=19, 2.8%) and gastrointestinal (N=8, 1.1%). Within the first 5 years of onset of SLE, neuropsychiatric damage was most frequent (10%), followed by renal (7.9%) and dermatological (7%) damage. In patients with SLE duration of more than 5 years, the commonest cause of damage was in the musculoskeletal system (18.4%), followed by neuropsychiatric (17%) and renal damage (13.3%). The presence of any organ damage was strongly and significantly associated with mortality (HR 6.42[3.05-13.5]; p<0.001). Cox regression analysis revealed that damage in the neuropsychiatric system (HR 1.74[1.31-2.32]; p<0.001), renal (HR 1.97 [1.61-2.42]; p<0.001), cardiovascular (HR 1.75 [1.21-2.53]; p=0.03) and pulmonary (HR 2.63 [1.50-4.62]; p=0.001) systems was significantly associated with mortality. Conclusions In patients with SLE, organ damage predicts mortality, in particular damage in the renal, nervous, cardiovascular and pulmonary systems. Neuropsychiatric damage is most common in early disease while musculoskeletal damage is most frequent in long-standing disease. Prevention of infective and cardiovascular complications, and minimization of renal damage is important in improving the survival of SLE. Disclosure of Interest None Declared

SAT0215 Clinical presentation, treatment and outcome of membranous nephropathy in SLE: A comparison with proliferative lupus glomerulonephritis in 141 patients

Objectives To study the presentation and outcome of membranous nephropathy in SLE in comparison with proliferative lupus glomerulonephritis. Methods Patients with biopsy firmed active lupus nephritis who were recruited in a randomized trial of mycophenolate mofetil (MMF) and tacrolimus (Tac) from 2005 to 2011 were studied. Participants were divided into 3 groups according to renal histology: group I (pure membranous lupus Gn:RPS/ISN class V); group 2 (mixed membranous/proliferative Gn: V+III or IVS/IVG) and group 3 (proliferative lupus Gn:IVS/IVG). The clinical presentation, treatment response, outcome were compared. Results 141 patients were studied (92%women; age 35.2±12.8 years, SLE duration 49.3±62 months). There were 25 (18%), 31 (22%) and 85 (60%) patients in group 1, 2 and 3, respectively. At presentation, group 1/2 patients had significantly higher hemoglobin (11.3±1.8vs9.9±1.7g/dL), creatinine clearance (CrCl) (90.0±31vs69.7±27ml/min), complement C3 level (0.62±0.27vs0.42±0.16g/L) but lower serum Cr (70.8±25vs91.5±33umol/L) and anti-dsDNA titer (166±116vs234±89IU/ml) than group 3 patients (p<0.001). 18 (32%) patients in group 1/2 had normal range C3 or anti-dsDNA, compared to 3 (4%) patients in group 3 (p<0.001). Nephrotic syndrome was more common in group 1/2 than group 3 patients (46% vs 32%; p=0.08) but the difference was no significant. Blood pressure and serum albumin level was similar among the 3 groups of patients. The SLE disease activity index (SLEDAI) score was significantly lower in group 1/2 than group 3 patients (13.5±4.9 vs 18.0±5.3 points;p<0.001). Extra-renal activity was less common in group 1/2 than group 3 patients, but the difference was only statistically significant for arthritis (25%vs42%;p=0.04). All patients were treated with high-dose prednisolone and either MMF (N=72) or Tac (N=69) assigned by random for induction, followed by low-dose prednisolone and azathioprine for maintenance (mean dose: 84.1±23mg/day). Complete response to induction treatment at 6 months, defined as urine P/Cr of <1.0, resolution of active urine sediments, improvement in lupus serology and stabilization of CrCl, was less common with group 1/2 than group 3 patients (45%vs62%;p=0.10). After an observation of 48.5±21 months, the cumulative risk of loss in 30% of CrCl compared to baseline was 4.6% at year 1, 6.3% at year 3 and 18% at year 5. Group 1/2 patients did not differ significantly from group 3 patients in terms of decline in CrCl (HR0.46[0.15-1.46];p=0.19, adjusted for age, sex, SLE duration, initial CrCl and treatment arms). There were 4 arterial events (2 acute coronary syndrome; 2 cerebrovascular accidents) and 1 venous event (deep vein thrombosis)- all occurred in group 1/2 patients (compared with group 3;p=0.01). Infections (major and minor) were numerically more common in group 1/2 than group 3 patients but the difference was insignificant. Conclusions The presence of histological membranous component in lupus nephritis is associated more proteinuria, better renal function but less active lupus serology or extra-renal activity at presentation. One-third of patients have either normal complements or anti-dsDNA, and complete response to induction therapy is less likely. Renal function decline in membranous lupus nephropathy is no different from proliferative lupus nephritis at 5 years, but thrombotic complications are more frequent. Disclosure of Interest None Declared

THU0170 The effect of the antiphospholipid syndrome (APS) on survival in 679 patients with sle: A prospective study

Objectives To study the effect of the antiphospholipid syndrome (APS) on survival in Chinese patients with SLE Methods A cohort of 679 southern Chinese patients who fulfill at least 4 of the ACR criteria for SLE from 1995 to 2011 was studied. The status of the patients at last clinical visits (alive or death) was evaluated. The cumulative survival rate over time was studied by Kaplan-Miere’s plot. For those who died during the course of their disease, data were censored at the time of their deaths whereas data of other patients were censored at the time of last clinic visits. APS was defined by the modified Sydney criteria in 2006, ie. presence of arterial or venous thrombosis, or miscarrages (recurrent abortion or intra-uterine death) plus any one of the following positive twice at least 12 weeks part: (1) lupus anticoagulant; (2) moderate to high titers of anticardiolipin antibodies (IgG or IgM); or (3) beta-2-glycoprotein-I. Comparison of the survival of patients with and without APS was made. Results 679 SLE patients were prospectively followed (623 women, 92%). The mean age of onset of SLE was 32.5±13.6 years and the mean follow-up time of the entire cohort of patients was 117±89 months. 67 (9.9%) patients died during the course of illness and 33 (4.9%) patients were lost to follow-up. The main contributing causes of death were: infection (51%), cardiovascular events (12%), cerebrovascular events (16%), and cancer (9%). 44 (6.5%) patients qualified the criteria for secondary APS. The clinical manifestations of APS in these patients were, in decreasing order of frequency, cerebrovascular accident (N=24, 55%), deep venous thrombosis (N=13, 30%), recurrent abortion/intrauterine fetal death (N=5, 11%), cardiovascular events (N=4, 9%) and peripheral vascular disease (N=4, 9%). Eight of 44 (18%) patients with APS died, which was more frequent in non-APS patients (59 deaths/635 patients, 9%; p=0.056). The cumulative mortality of patients with APS was 4.7% at 5 years, 7.8% at 10 years and 22.2% at 15 years, whereas the cumulative mortality of patients without APS was 5.2% at 5 years, 8.8% at 10 years and 10.9% at 15 years. Although the survival of APS patients was poorer than those without APS, the difference did not reach statistical significance (log rank test; p=0.23). However, if patients with APS involving only arterial thrombosis were considered, the presence of APS was significantly associated with mortality (HR 2.11 [1.004-4.45]; p=0.049). Conclusions The presence of APS increases the mortality risk of patients with SLE, which is mainly contributed by arterial thrombotic events that occur late in the disease course. Disclosure of Interest None Declared