O16 A study examining the reliability of digital ulcer definitions as proposed by the UK Scleroderma Study Group: challenges and insights for future clinical trial design

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The BILAG-2004 index is associated with development of new damage in SLE

OBJECTIVE: To determine whether BILAG-2004 index is associated with the development of damage in a cohort of SLE patients. Mortality and development of damage were examined.METHODS: This was a multicentre longitudinal study. Patients were recruited within 12 months of achieving 4th ACR classification criterion for SLE. Data were collected on disease activity, damage, SLE-specific drug exposure, cardiovascular risk factors, antiphospholipid syndrome status and death at every visit. This study ran from 1st January 2005 to 31st December 2017. Descriptive statistics were used to analyse mortality and development of new damage. Poisson regression was used to examine potential explanatory variables for development of new damage.RESULTS: 273 SLE patients were recruited with total follow-up of 1767 patient-years (median 73.4 months). There were 6348 assessments with disease activity scores available for analysis. During follow-up, 13 deaths and 114 new damage items (in 83 patients) occurred. The incidence rate for development of damage was higher in the first 3 years before stabilising at a lower rate. Overall rate for damage accrual was 61.1 per 1000 person-years (95% CI : 50.6, 73.8). Analysis showed that active disease scores according to BILAG-2004 index (systems scores of A or B, counts of systems with A and BILAG-2004 numerical score) were associated with development of new damage. Low disease activity (LDA) states (BILAG-2004 LDA and BILAG Systems Tally (BST) persistent LDA) were inversely associated with development of damage.CONCLUSIONS: BILAG-2004 index is associated with new damage. BILAG-2004 LDA and BST persistent LDA can be considered as treatment targets.</p

Numerical scoring for the BILAG-2004 index

Objective. To develop an additive numerical scoring scheme for the BILAG-2004 index

Reliability of digital ulcer definitions as proposed by the UK Scleroderma Study Group:A challenge for clinical trial design

INTRODUCTION: The reliability of clinician grading of systemic sclerosis–related digital ulcers has been reported to be poor to moderate at best, which has important implications for clinical trial design. The aim of this study was to examine the reliability of new proposed UK Scleroderma Study Group digital ulcer definitions among UK clinicians with an interest in systemic sclerosis. METHODS: Raters graded (through a custom-built interface) 90 images (80 unique and 10 repeat) of a range of digital lesions collected from patients with systemic sclerosis. Lesions were graded on an ordinal scale of severity: ‘no ulcer’, ‘healed ulcer’ or ‘digital ulcer’. RESULTS: A total of 23 clinicians – 18 rheumatologists, 3 dermatologists, 1 hand surgeon and 1 specialist rheumatology nurse – completed the study. A total of 2070 (1840 unique + 230 repeat) image gradings were obtained. For intra-rater reliability, across all images, the overall weighted kappa coefficient was high (0.71) and was moderate (0.55) when averaged across individual raters. Overall inter-rater reliability was poor (0.15). CONCLUSION: Although our proposed digital ulcer definitions had high intra-rater reliability, the overall inter-rater reliability was poor. Our study highlights the challenges of digital ulcer assessment by clinicians with an interest in systemic sclerosis and provides a number of useful insights for future clinical trial design. Further research is warranted to improve the reliability of digital ulcer definition/rating as an outcome measure in clinical trials, including examining the role for objective measurement techniques, and the development of digital ulcer patient–reported outcome measures

The BILAG-2004 systems tally-a novel way of representing the BILAG-2004 index scores longitudinally

Objective. This was an exploratory analysis to develop a new way of representing BILAG-2004 system scores longitudinally that would be clinically meaningful and easier to analyse in comparison with multiple categorical variables. Methods. Data from a multicentre longitudinal study of SLE patients (the BILAG-2004 index and therapy collected at every visit) were used. External responsiveness analysis of the index suggested the possibility of using counts of systems with specified transitions in scores as a basis to analyse the system scores. Exploratory analyses with multinomial logistic regression were used to examine the appropriateness of this new method of analysing BILAG-2004 system scores. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of this approach. Results. There were 1414 observations from 347 patients. A novel method was devised based on counts of systems with defined transitions in score (BILAG-2004 systems tally, BST). It has six components (systems with major deterioration, systems with minor deterioration, systems with persistent significant activity, systems with major improvement, systems with minor improvement and systems with persistent minimal or no activity). This was further simplified (simplified BST, sBST) into three components (systems with active/worsening disease, systems with improving disease and systems with persistent minimal or no activity). Both versions had expected associations with change in therapy. ROC curve analyses demonstrated that both versions had similar good performance characteristics (areas under the curve >0.80) in predicting increase in therapy. Conclusion. The BST and sBST provide alternative approaches to representing BILAG-2004 disease activity longitudinally. Further validation of their use is required

Management of systemic sclerosis: British Society for Rheumatology guideline scope

This guideline will provide a practical roadmap for management of SSc that builds upon the previous treatment guideline to incorporate advances in evidence-based treatment and increased knowledge about assessment, classification and management. General approaches to management as well as treatment of specific complications will be covered, including lung, cardiac, renal and gastrointestinal tract disease, as well as RP, digital vasculopathy, skin manifestations, calcinosis and impact on quality of life. It will include guidance related to emerging approved therapies for interstitial lung disease and account for National Health Service England prescribing policies and national guidance relevant to SSc. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence accreditation

Management of systemic sclerosis: British Society for Rheumatology guideline scope

This guideline will provide a practical roadmap for management of SSc that builds upon the previous treatment guideline to incorporate advances in evidence-based treatment and increased knowledge about assessment, classification and management. General approaches to management as well as treatment of specific complications will be covered, including lung, cardiac, renal and gastrointestinal tract disease, as well as RP, digital vasculopathy, skin manifestations, calcinosis and impact on quality of life. It will include guidance related to emerging approved therapies for interstitial lung disease and account for National Health Service England prescribing policies and national guidance relevant to SSc. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence accreditation

Prevalence and risk factors for pulmonary arterial hypertension in patients with lupus

Background: Pulmonary arterial hypertension (PAH) is a recognised complication of SLE. The risk of developing PAH in SLE may be increased in a subset of patients with antiphospholipid antibodies. Aims: To estimate the point prevalence of PAH, to evaluate screening tests and to identify risk factors for PAH in a large cohort of SLE patients Methods: A prospective cross-sectional study of 288 patients with SLE using resting transthoracic echocardiography to estimate the systolic pulmonary artery pressures (sPAP) and to assess cardiac morphology and function. We assessed potential risk factors such as the presence of lung disease, autoantibodies and anti-phospholipid syndrome (APS). We evaluated screening tests such as pulmonary function tests, six minute walk test and biomarkers. Results: Twelve out of 283 patients had PAH with sPAP >30 mm Hg (range 31-59 mmHg). Only 3 patients had sPAP >40 mm Hg. The only significant risk factor for PAH was lupus anticoagulant (p=0.005). Conclusion: The point prevalence of PAH was 4.2% in our cohort of patients with SLE. The significant association of lupus anticoagulant and presence of APS in PAH cases suggests that thrombosis may play an important role in the development of PAH with SLE patients