Vera Golder

Association of Asian ethnicity with disease activity in SLE: an observational study from the Monash Lupus Clinic.

Objective Systemic lupus erythematosus (SLE), an autoimmune condition with diverse clinical manifestations, is reported to have different expression in populations of different ancestry. Most previous studies compared patients of different ethnic groups from geographically distinct cohorts. In our study, we aimed to characterize disease manifestations in patients of different ethnic groups from a single centre, and studied patterns of disease activity over time. Methods Demographics, baseline disease characteristics and autoantibody profiles, and disease activity (SLEDAI) measured at each visit, were captured from all consenting patients prospectively followed between 2007 and 2011 in an urban teaching hospital lupus clinic. Ethnicity was self-reported. Results Asian ethnicity was significantly associated with more clinically severe SLE. Time-adjusted mean SLEDAI (p = 0.01) and maximum SLEDAI (p = 0.0018) were significantly higher in Asian patients. Asians were more likely to have renal disease (OR 2.9, 95% CI 1.4–5.98; p = 0.004) and persistently active disease (PAD) (OR 2.14, 95% CI 1.05–4.38, p = 0.04). Asian lupus patients also had a significantly higher proportion of autoantibody positivity to anti-dsDNA, anti-RNP, anti-Sm, anti-Ro and anti-La, as well as increased likelihood of hypocomplementaemia and immunosuppressant use. Conclusion In this single-cohort study, Asian ethnicity was found to be associated with increased SLE disease activity. This suggests significant inter-ethnic genetic contributions to the regulation of autoimmune responses and disease severity in SLE.

Systemic lupus erythematosus: an update

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease predominantly affecting women of childbearing age. New classification criteria for SLE have greater sensitivity and therefore improve the diagnostic certainty for some patients, especially those who may previously have been labelled as having undifferentiated symptoms. Uncontrolled disease activity leads to irreversible end‐organ damage, which in turn increases the risk of premature death; early and sustained control of disease activity can usually be achieved by conventional immunosuppressant therapy. The development of biological therapy lags behind that for other rheumatic diseases, with belimumab being the only targeted therapy approved by the Therapeutic Goods Administration. “Treat‐to‐target” concepts are changing trial design and clinical practice, with evidence‐based definition of response criteria in the form of remission and low disease activity now on the horizon. While new therapies are awaited, research should also focus on optimising the use of current therapy and improving the quality of care of patients with SLE.

Discordance of patient and physician health status concerns in systemic lupus erythematosus

Objectives To compare the health status concerns of patients with systemic lupus erythematosus (SLE) and of their physicians. Methods Cross-sectional questionnaire study of SLE patients and their treating physicians at a tertiary disease-specific outpatient clinic. Patients and physicians completed a questionnaire regarding their concern about specific disease manifestations and impact on quality of life. For each item, degree of concern was rated on a five-point Likert scale and summarized as median (interquartile range). Ratings between patients and physicians were compared using Mann–Whitney U tests. Results A total of 84 patients and 21 physicians participated. Patients’ predominant concerns centred on function and fatigue, whereas physicians’ concerns focused on SLE-related organ complications. Of the 10 highest ranked patient concerns, only two were common to the 10 highest ranked physician concerns, while physicians rated seven significantly differently; all 10 highest ranked physician concerns were rated significantly lower by patients. The three highest ranked patient concerns (fatigue, pain and feeling worn out) were routinely assessed by 47.6%, 42.9% and 9.5% of physicians, respectively. Conclusion There was significant discordance between SLE patient and physician health status concerns. Items which were ranked highly by patients were not assessed consistently by physicians, highlighting a significant gap in healthcare communication.

Does expert opinion match the operational definition of the Lupus Low Disease Activity State (LLDAS)? A case-based construct validity study

OBJECTIVE To evaluate the construct validity of the Lupus Low Disease Activity State (LLDAS), a treatment target in systemic lupus erythematosus (SLE). METHODS Fifty SLE case summaries based on real patients were prepared and assessed independently for meeting the operational definition of LLDAS. Fifty international rheumatologists with expertise in SLE, but with no prior involvement in the LLDAS project, responded to a survey in which they were asked to categorize the disease activity state of each case as remission, low, moderate, or high. Agreement between expert opinion and LLDAS was assessed using Cohens kappa. RESULTS Overall agreement between expert opinion and the operational definition of LLDAS was 77.96% (95% CI: 76.34-79.58%), with a Cohens kappa of 0.57 (95% CI: 0.55-0.61). Of the cases (22 of 50) that fulfilled the operational definition of LLDAS, only 5.34% (59 of 22 × 50) of responses classified the cases as moderate/high activity. Of the cases that did not fulfill the operational definition of LLDAS (28 of 50), 35.14% (492 of 28 × 50) of responses classified the cases as remission/low activity. Common reasons for discordance were assignment to remission/low activity of cases with higher corticosteroid doses than defined in LLDAS (prednisolone ≤ 7.5mg) or with SLEDAI-2K >4 due to serological activity (high anti-dsDNA antibody and/or low complement). CONCLUSIONS LLDAS has good construct validity with high overall agreement between the operational definition of LLDAS and expert opinion. Discordance of results suggests that the operational definition of LLDAS is more stringent than expert opinion at defining a low disease activity state.

Disseminated Enteroviral Infection Associated with Obinutuzumab

Two cases of disseminated enteroviral infection occurred in patients who received the CD20 monoclonal antibody obinutuzumab. Clinical features included hepatitis, edema, and a dermatomyositis-like syndrome. These manifestations may be unfamiliar to clinicians and are possibly responsive to intravenous immunoglobulin. Clinicians should remain vigilant for enteroviral infections in patients receiving obinutuzumab.

Quality of Care for Systemic Lupus Erythematosus: Mind the Knowledge Gap

Systemic lupus erythematosus (SLE) is a prototypical chronic multiorgan autoimmune disorder that can lead to significant burden of disease and loss of life expectancy. The disease burden is the result of a complex interplay between genetic, biologic, socioeconomic, and health system variables affecting the individual. Recent advances in biological understanding of SLE are yet to translate to transformative therapies, and genetic and socioeconomic variables are not readily amenable to intervention. In contrast, healthcare quality, a variable readily amenable to change, has been inadequately addressed in SLE, despite evidence in other chronic diseases that quality of care is strongly associated with patient outcomes. This article will analyze the available literature on the quality of care relevant to SLE, identify knowledge gaps, and suggest ways to address this in future research.

454 Discordance of patient and physician health status concerns in systemic lupus erythematosus

Background and aims To investigate and compare the health status concerns of physicians and patients with systemic lupus erythematosus (SLE). Methods Patients and their treating physicians completed a questionnaire asking their concern for specific disease manifestations and disease impact on quality of life. For each item, degree of concern was measured on a 5-point Likert scale. Sub-groups were compared by Kruskal-Wallis test for significance. Results A total of 84 patients and 21 physicians participated. Patients were predominantly concerned with function and fatigue, whereas physicians focussed on organ complications of SLE. Seven out of the top 10 patient concerns showed statistically significant differences to physician ratings, including “reduced ability to perform activities of daily living (ADLs)” (p=0.02) and “reduced ability to perform physical activities” (p=0.04). All the top 10 physician concerns showed statistically significant differences to patient ratings, including “seizures” (p=0.003) and “stroke” (p=0.002). The top 3 patient concerns were routinely assessed by 47.6%, 42.9% and 9.5% of physicians, respectively. Top 10 patient concerns: Top 10 physician concerns: Abstract 454 Table 1 Abstract 454 Table 2 Conclusions There was significant discordance between patient and physician health status concerns. Items which were ranked highly by patients were systematically underestimated by physicians, highlighting an urgent need to improve communication. Further studies could explore ways within the healthcare interaction that could improve patient satisfaction and disease control.

437 Construct validity assessment of the lupus low disease activity state (lldas) – a case based validity study

Background and aims To evaluate the construct validity of the Lupus Low Disease Activity State (LLDAS), a treatment target in systemic lupus erythematosus (SLE). Methods Fifty SLE case summaries based on real patients were prepared and assessed independently for meeting the operational definition of LLDAS. Fifty international rheumatologists with expertise in SLE, but with no prior involvement in the LLDAS project, responded to a survey in which they were asked to categorise the disease activity state of each case as remission, low, moderate or high. Agreement between expert opinion and LLDAS was assessed using Cohen’s Kappa. Results Overall agreement between expert opinion and the operational definition of LLDAS was 77.96% (95% CI 76.34%–79.58%), with a Cohen’s Kappa of 0.57 (95% CI 0.55–0.61). Of the cases (22 of 50) that fulfilled the operational definition of LLDAS, only 5.34% (59 of 22 × 50) of responses classified the cases as moderate/high activity. Of the cases that did not fulfil the operational definition of LLDAS (28 of 50), 35.14% (492 of 28 × 50) of responses classified the cases as remission/low activity. Common reasons for discordance were assignment to remission/low activity of cases with higher corticosteroid doses than defined in LLDAS (prednisolone ≤7.5 mg) or with SLEDAI-2K>4 due to serological activity (high anti-dsDNA antibody and/or low complement). Conclusions LLDAS has good construct validity with high overall agreement between the operational definition of LLDAS and expert opinion. Discordance of results suggests that the operational definition of LLDAS is more stringent than expert opinion at defining a low disease activity state.

33 Association of the lupus low disease activity state (lldas) with health related quality of life

Background and Aims Systemic lupus erythematosus (SLE) is associated with significant impairment of health-related quality of life (HR-QoL). The Lupus Low Disease Activity State (LLDAS) definition has not been previously evaluated for association with patient reported outcomes. The objective of this study was to determine whether LLDAS was associated with better HR-QoL, and examine predictors of HR-QoL, in a large multiethnic, multinational cohort of SLE patients. Methods HR-QoL was measured using the Medical Outcomes Study 36-item Short Form Health Survey (SF-36v2) in a prospective study of 1422 patients. Disease status was measured using SLE disease activity index (SLEDAI-2K), physician global assessment (PGA) and LLDAS. Results Significant differences in SF-36 domain scores were found between patients stratified by ethnic group, education level, damage score, and with the presence of active musculoskeletal or cutaneous manifestations. In multiple linear regression analysis, Asian ethnicity (p<0.001), a higher level of education (p<0.001), younger age (p<0.001) and shorter disease duration (p<0.01) remained significantly associated with better physical component scores (PCS). Musculoskeletal disease activity (p<0.001) was negatively associated with PCS, and cutaneous activity (p=0.04) was negatively associated with mental component scores (MCS). Patients in LLDAS had better PCS (p<0.001) and MCS (p<0.001) scores and significantly better scores in multiple individual SF-36 domain scores. Disease damage was associated with worse PCS (p<0.001), but not MCS scores. Conclusions Ethnicity, education, disease damage, and specific organ involvement impacts on HR-QoL in SLE. Attainment of LLDAS is associated with better HR-QoL.

SAT0282 Frequency and Predictors of Attainment of The Lupus Low Disease Activity State (LLDAS) in A Cross Sectional Study of Sle Patients in The Asia Pacific

Background Systemic lupus erythematosus (SLE) is a heterogeneous disease characterised by fluctuating disease activity. A low disease activity endpoint, the Lupus Low Disease Activity State (LLDAS), was recently reported and retrospective validation showed that time spent in LLDAS translated into reduced damage accrual (Franklyn, Ann Rheum Dis, 2015). A large prospective study to validate LLDAS in a multiethnic cohort of lupus patients from the Asia Pacific Region is underway. Objectives To describe the frequency and identify the predictors of fulfilling criteria for LLDAS in baseline visit data from a large multinational multiethnic cohort of patients with SLE in nine Asia Pacific countries. Methods Prospectively collected baseline visit data from 1846 SLE patients enrolled in a longitudinal study were analysed cross sectionally against the recently published definition of LLDAS, and patient characteristics associated with LLDAS attainment determined. Results LLDAS criteria were met by 44% of patients at a single baseline visit. Stepwise multivariable logistic regression revealed that patients with shorter disease duration were less likely to be in LLDAS (OR 0.31, 95% CI 0.19–0.49, p<0.001). Likewise, discoid rash (OR 0.66, 95% CI 0.49–0.89, p=0.006), renal disease (OR 0.60, 95% CI 0.48–0.75, p<0.001), elevated double stranded DNA (OR 0.65, 95% CI 0.53–0.81, p<0.001) or hypocomplementaemia (OR 0.52, 95% CI 0.40–0.67, p<0.001) were negatively associated with LLDAS attainment. Significant differences in LLDAS attainment between countries were observed, and higher national social wealth as measured by the Gross Domestic Product per capita was positively associated with LLDAS (OR 1.57, 95% CI 1.25–1.98, p<0.001). Conclusions Low disease activity was observed in less than half of SLE patients at a single point in time. Disease duration and phenotype, as well as national social wealth, were predictive of LLDAS attainment. Disclosure of Interest None declared