AB0633 Measuring what matters to lupus patients: translating patient views into novel patient-reported outcomes

Background The 2010 U.S. FDA guidance1 on systemic lupus erythematosus (SLE) acknowledged that ‘improvements in clinical outcome measures in patients with SLE may not always translate to improvements in how patients feel or function’ and encourages the use of patient-reported outcome instruments (PROs) to assess changes in outcomes that matter most to patients. Fatigue, identified by patients as their chief complaint during the Lupus Patient-Focused Drug Development (PFDD) meeting2, is not optimally measured by existing PROs1. There is a need for new patient-centred outcome measures as they are pivotal to PFDD. To address this, UCB has been conducting a multi-faceted, patient-centric, mixed methods research programme including evidence generated from >2100 SLE patients. Objectives There were three main objectives of the programme: 1) identify what concepts are most important to measure for SLE patients when evaluating treatment benefit; 2) critically evaluate the extent to which these concepts are captured by existing PROs; and 3) explore the opportunity to develop and evaluate new conceptually-based PROs in SLE. Methods There were three stages: 1) development of a preliminary treatment benefit conceptual model related to SLE including disease symptoms and impacts (generated from literature review, and patient and clinician input); 2) formal comparison of i) the conceptual model and the content validity (qualitative review) of existing SLE PROs and ii) psychometric properties (ie. SF-36, FACIT-F, and LupusQoL in the discontinued EMBODY Phase 3 studies for epratuzumab); 3) development of new conceptually-based PROs in SLE (figure 1). Results A preliminary treatment benefit conceptual model in SLE was developed. Among the many symptoms and disease impacts reported by SLE patients, physical fatigue, mental fatigue (‘brain fog’), sudden fatigability, joint/muscle stiffness and pain, skin symptoms and mobility difficulties featured as most troublesome. The content validity of 10 widely used PROs was found to be limited when compared to this conceptual model. Psychometric analysis (based on Rasch Measurement Theory) confirmed the limitations of the SLE PROs used in the EMBODY studies and suggested post-hoc reconceptualisation would improve the ability of the scales to detect clinical change. This led to the development of five new conceptually-based SLE PROs (ie. fatigue, pain, mobility, symptom severity, and emotional state), which are currently being explored in >500 SLE patients in a Phase 2b dapirolizumab pegol study (NCT02804763) and two cross-sectional, non-interventional, observational studies. Data on the new PROs are currently being assessed at several sites in the USA, Latin America, UK and Germany and will be available in the coming months. Conclusions New, well-defined and reliable PROs to better capture the patient perceptions of the symptoms and impact of SLE are needed. UCB has developed five new PROs which offer the promise of improved patient-centred outcome measurements in SLE and other autoimmune diseases. References [1] Food and Drug Administration. Guidance for Industry. Systemic Lupus Erythematosus. June 2010. [2] Lupus Patient-Focused Drug Development meeting, 25 September 2017. Disclosure of Interest S. Cleanthous Employee of: Modus Outcomes Ltd, A. Regnault Employee of: Modus Outcomes Ltd, M. Schneider Consultant for: UCB Pharma, C. Gordon Grant/research support from: UCB Pharma, Consultant for: UCB, Merck Serono, GSK, S. Bartlett: None declared, S. Cano Shareholder of: Modus Outcomes Ltd, Employee of: Modus Outcomes Ltd, T. Morel Shareholder of: UCB Pharma, Employee of: UCB Pharma