C.C. Mok

Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality.

Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease with a wide spectrum of manifestations, shows considerable variation across the globe, although there is little evidence to indicate its relative prevalence in Asia. This review describes its prevalence, severity, and outcome across countries in the Asia‐Pacific region.

Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus.

OBJECTIVE To study the effect of renal disease on the standardized mortality ratio (SMR) and life expectancy of patients with systemic lupus erythematosus (SLE). METHODS Patients whose diagnosis met ≥4 American College of Rheumatology criteria for SLE were longitudinally followed up from 1995 to 2011. The cumulative survival rate, SMR, and life expectancy were calculated, and the effect of renal involvement, histologic class of lupus nephritis, renal damage, and end-stage renal disease (ESRD) on these parameters was evaluated. RESULTS Of the 694 SLE patients studied, 368 (53%) had renal disease, and the distribution of histologic classes (among 285 patients) was class I (1%), class II (6%), class III (19%), class IV (47%), class III/IV + class V (10%), and class V (16%). Renal damage was present in 79 patients (11%), and 24 (3%) developed ESRD. The age- and sex-adjusted hazard ratios (HRs) of mortality in SLE patients with renal disease, those with renal damage, and those with ESRD, as compared to those without, were 2.23 (95% confidence interval [95% CI] 1.29-3.85), 3.59 (95% CI 2.20-5.87), and 9.20 (95% CI 4.92-17.2), respectively. Proliferative lupus nephritis (adjusted HR 2.28, 95% CI 1.22-4.24), but not the pure membranous type (adjusted HR 1.09, 95% CI 0.38-3.14), was associated with a significant increase in mortality. The age- and sex-adjusted SMRs of SLE patients without renal involvement, those with lupus nephritis, those with proliferative nephritis, those with pure membranous nephritis, those with renal damage, and those with ESRD were 4.8 (95% CI 2.8-7.5), 9.0 (95% CI 6.7-11.9), 9.8 (95% CI 6.5-14.1), 6.1 (95% CI 2.0-14.1), 14.0 (95% CI 9.1-20.5), and 63.1 (95% CI 33.6-108.0), respectively. The life expectancy of SLE patients with renal disease and those with renal damage was reduced by 15.1 years and 23.7 years, respectively, compared to the general population. CONCLUSION The presence of renal disease, in particular proliferative nephritis causing renal insufficiency, significantly reduces the survival and life expectancy of SLE patients.

Vitamin D deficiency as marker for disease activity and damage in systemic lupus erythematosus: a comparison with anti-dsDNA and anti-C1q

Objectives: To study the sensitivity and specificity of vitamin D deficiency for predicting disease activity and damage of systemic lupus erythematosus (SLE) in comparison with anti-dsDNA and anti-C1q. Methods: Consecutive patients who fulfilled four or more ACR criteria for SLE were studied. Levels of 25-hydroxyvitamin D3, anti-C1q, anti-dsDNA and complement levels were measured. Relationship among these markers, concurrent disease activity and damage scores of SLE was studied by Spearmans rank correlation method. Results: In total, 290 SLE patients were studied (95% women; mean age 38.9 ± 13.1 years; SLE duration 7.7 ± 6.7 years). Clinical or serological lupus activity (SLEDAI ≥ 1) was present in 225 (78%) patients. Vitamin D deficiency (< 15 ng/ml) was detected in 78 (27%) patients. Levels of 25-hydroxyvitamin D3 correlated inversely with the clinical SLE disease activity score (Rho = −0.26; p < 0.001). A negative correlation was also observed between 25-hydroxyvitamin D3 and anti-dsDNA levels (Rho = −0.13; p = 0.02), or anti-C1q (Rho = −0.14; p = 0.02). However, there was no significant relationship between levels of 25-hydroxyvitamin D3 and complement C3 (Rho = 0.09; p = 0.12) or C4 (Rho = 0.09; p = 0.13). Both 25-hydroxyvitamin D3 deficiency and anti-C1q were more specific but less sensitive than anti-dsDNA for concurrent clinical renal and non-renal SLE activity. Levels of 25-hydroxyvitamin D3, anti-dsDNA or anti-C1q did not correlate significantly with the SLE damage scores. Conclusions: 25-hydroxyvitamin D3 correlated inversely and significantly with clinical SLE activity, anti-C1q and anti-dsDNA titers, but not with complement levels or damage scores. Deficiency of 25-hydroxyvitamin D3 was as specific as anti-C1q, but less sensitive than anti-dsDNA, for detecting concurrent renal and non-renal clinical activity of SLE.

Anti–müllerian hormone and ovarian reserve in systemic lupus erythematosus

OBJECTIVE To study the level of anti-müllerian hormone (AMH) and its relationship to age and previous exposure to cyclophosphamide (CYC) in patients with systemic lupus erythematosus (SLE). METHODS Consecutive female patients ages 18-52 years who had menses at least once during the preceding 12 months and fulfilled ≥4 American College of Rheumatology criteria for SLE were recruited. AMH was determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum AMH levels were compared in patients with and without previous use of immunosuppressive agents. The relationship of the AMH level to the patients age and CYC exposure was studied by linear regression and receiver operating characteristic (ROC) curve analysis. RESULTS A total of 216 patients were studied (mean±SD age 35.1±10.1 years, mean±SD SLE duration 7.6±5.9 years). The mean±SD AMH level was significantly lower in patients previously exposed to CYC therapy than in those who had not been exposed after adjustment for age (1.58±2.92 versus 1.73±2.11 ng/ml; P=0.04). The median time interval between the AMH assay and the last dose of CYC administered was 6.7 years (interquartile range 3.4-8.5). AMH levels in users versus nonusers of other immunosuppressive agents, including mycophenolate mofetil, azathioprine, and the calcineurin inhibitors, were not statistically different. Linear regression revealed increasing age (beta -0.32, P=0.02) and each 5 gm of CYC exposure (beta -0.28, P=0.047) were independently associated with a lower AMH level. In patients ages 30 years and younger, a cumulative CYC dose cutoff of 5.9 gm yielded a sensitivity of 0.75 and a specificity of 0.80 for the prediction of undetectable AMH level on ROC curve analysis. CONCLUSION AMH is a sensitive marker for ovarian damage due to previous CYC exposure in women with SLE.

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.

Improved health outcomes with Etanercept versus usual DMARD therapy in an Asian population with established rheumatoid arthritis

BackgroundPatient reported outcomes (PROs) are especially useful in assessing treatments for rheumatoid arthritis (RA) since they measure dimensions of health-related quality of life that cannot be captured using strictly objective physiological measures. The aim of this study was to compare the effects of combination etanercept and methotrexate (ETN + MTX) versus combination synthetic disease modifying antirheumatic drugs (DMARDs) and methotrexate (DMARD + MTX) on PRO measures among RA patients from the Asia-Pacific region, a population not widely studied to date. Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied.MethodsPatients were randomized to either ETN + MTX (N = 197) or DMARD + MTX (N = 103) in an open-label, active-comparator, multicenter study, with PRO measures designed as prospective secondary endpoints. The Health Assessment Questionnaire (HAQ), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue), Medical Outcomes Short Form-36 Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS) and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH) were used.ResultsSignificantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5, compared to patients in the DMARD + MTX group. SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms. Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue, HADS, and WPAI:GH mean scores.ConclusionCombination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures, compared to combination therapy with usual standard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region.Trial registrationclintrials.gov # NCT00422227

High sensitivity C-reactive protein, disease activity and cardiovascular risk factors in systemic lupus erythematosus

To study the level of high‐sensitivity C‐reactive protein (hsCRP) and its relationship with disease activity, damage, and cardiovascular risk factors in patients with systemic lupus erythematosus (SLE).

The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study

Objective To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes. Methods This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6–24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected. Results Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low. Conclusion ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA. Trial registration This study was registered on www.ClinicalTrials.gov (NCT01981473).

Disease-specific quality of life in patients with lupus nephritis

Background Patient-reported outcomes in lupus nephritis (LN) are not well studied. Studies with disease-targeted PRO tool in LN do not exist. Herein, we describe quality of life (QOL: HRQOL & non-HRQOL) among LN patients using LupusPRO. Methods International, cross-sectional data from 1259 patients with systemic lupus erythematosus (SLE) and LupusPRO were compared, stratified by (a) presence of LN (ACR classification criteria (ACR-LN)) at any time and, (b) active LN (on SLEDAI) at study visit. Damage was assessed by SLICC/ACR-SDI. Multivariate regression analyses for QOL against ACR-LN (active LN) after adjusting for age, gender, ethnicity and country of recruitment were performed. Results Mean (SD) age was 41.7 (13.5) yrs, 93% were women. Five hundred and thirty-nine of 1259 SLE patients had ACR-LN. ACR-LN group was younger, were more often on immunosuppressive medications, had worse QOL on lupus medications and procreation than non-ACR-LN patients. HRQOL and non-HRQOL scores were similar in both groups. One hundred and twenty-nine of 539 ACR-LN patients had active LN. Active LN group was younger, had greater disease activity and had worse HRQOL and non-HRQOL compared to patients without active LN. Specific domains adversely affected were lupus symptoms, lupus medications, procreation, emotional health, body image and desires-goals domains. Patients with ACR-LN and active LN fared significantly worse in lupus medications and procreation HRQOL domains, even after adjusting for age, ethnicity, gender and country of recruitment. Conclusions Lupus nephritis patients have poor QOL. Patients with active LN have worse HRQOL and non-HRQOL. Most domains affected are not included in the generic QOL tools used in SLE. LN patients must receive discussion on lupus medications and procreation issues. Patients with active LN need comprehensive assessments and addressal of QOL, along with treatment for active LN.

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