Issues Affecting Quality of Life and Disease Burden in Lipoprotein Lipase Deficiency (Lpld) - First Step Towards a Pro Measure in Lpld

Abstract

Objectives: LPLD is an ultra-orphan genetic lipid disorder (prevalence 1-2/million). It is associated with severe hypertriglyceridemia and an increased risk of acute pancreatitis. Other manifestations include eruptive xanthoma, fatigue, difficulty with concentrating and cardiopulmonary symptoms. Associated symptoms, complications and the fat-restricted diet affect Quality of Life (QOL). Currently no disease-specific measure exists to assess QOL and the burden of LPLD. As part of post approval commitments of alipogene tiparvovec, regulatory bodies requested the development of a reliable measure of QOL in LPLD. This study evaluates existing EORTC questionnaires QLQ-C30 and QLQ-PAN26, and a new questionnaire of disease burden devised by clinicians with experience in treating LPLD. Methods: To date, eight genetically confirmed LPLD-patients from four countries assessed the relevance and importance of each item of the three questionnaires. Patients’ ratings were discussed during an in-depth, face-to-face interview and the disease burden questionnaire was comprehensively discussed, analyzed and then modified where necessary. Results: Quantitative assessment showed that 25 (45%) of the QLQ-C30 and QLQ-PAN26 questions were relevant to the majority of patients. The most relevant items were pain (6), fatigue and sleeping problems (4), digestive and dietary factors (4), work, daily and social activity restrictions (4) and impact on emotional functioning (3). Qualitative and quantitative analysis of the new questionnaire highlighted the unpredictability of pancreatitis attacks and the impact of the strict low fat diet on social and emotional factors. Less common clinical manifestations of LPLD (xanthoma, dyspnea) were very important to those affected. The new questionnaire has been modified and items on alcohol use and painkillers added for ongoing evaluation. Conclusions: Five QOL domains relevant to LPLD have been identified using existing questionnaires. A new disease-specific questionnaire identifies significant impacts on patients’ lives. These instruments may help clinicians to effectively use pharmacological and genetic therapy to manage LPLD patients.