Effects of Metreleptin on Patient Outcomes and Quality of Life in Generalized and Partial Lipodystrophy

Cook, Keziah; Adamski, Kelly; Gomes, Aparna; Tuttle, Edward; Kalden, Henner; Cochran, Elaine; Brown, Rebecca

doi:10.1210/jendso/bvab019

Cited by 25 publications

(19 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients treated with metreleptin experienced statistically significant improvement in metabolic parameters across various subgroups (GL, PL, PL with severe metabolic complications) after controlling for baseline concomitant medication usage. These findings are also consistent with other research that found metreleptin led to statistically significant improvement in prevalent comorbidities in patients with lipodystrophy 18 .…”

Section: Discussionsupporting

confidence: 92%

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Adamski

Cook

Gupta

et al. 2021

Current Medical Research and Opinion

Self Cite

View full text Add to dashboard Cite

Objective: To evaluate the effects of metreleptin in distinct subgroups of patients with generalized lipodystrophy (GL) and partial lipodystrophy (PL), using multivariate linear regression modeling to account for the role of patients' baseline usage of concomitant glucose and lipid-lowering medications and other covariates on their outcomes. Materials and methods: A post-hoc statistical analysis of two published single-arm, interventional, phase 2 clinical trials at NIH was conducted. Concomitant medication use was assessed for the clinical trial population using prescription fill data, measured at baseline and the post-one year following metreleptin initiation. Pre-specified co-primary efficacy endpoints measured were change from baseline in HbA1c at month 12, and the percent change from baseline in fasting serum triglycerides (TG) at month 12. Descriptive and statistical analyses were conducted for the overall population, the separate populations with GL and PL, and additional PL subgroups defined by baseline metabolic markers of elevated HbA1c and elevated fasting TG. Results: As previously reported, improvement in HbA1c and fasting TG from baseline to 12 months on metreleptin were observed in the overall population (mean change À1.57 percentage points and median change À37.9%, respectively) and subgroups. For both HbA1c and TG, baseline levels were significant predictors of changes after metreleptin. After considering baseline characteristics such as disease type, age, sex, and baseline HbA1c, baseline insulin use was not found to be a significant predictor of HbA1c improvement following metreleptin initiation. Similar results were seen for TG levels, with the use of any lipid-lowering medications at baseline not found to be a significant predictor of reductions in fasting TG levels. Conclusions: Patients treated with metreleptin experienced statistically significant improvement in metabolic markers of glycemic and hypertriglyceridemic control-e.g. HbA1c and triglyceride levelsacross various subgroups after controlling for baseline characteristics and concomitant medication usage.

show abstract

Section: Discussionsupporting

confidence: 92%

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Adamski

Cook

Gupta

et al. 2021

Current Medical Research and Opinion

Self Cite

View full text Add to dashboard Cite

show abstract

“…This can lead to targeted therapies and allow patients to avoid additional burdens of frustration and medical complications that can be caused by failed weight loss interventions [ 22 ]. Weight loss and hunger reduction are important for individuals with obesity and hyperphagia because they can lead to improvements in QOL [ 26 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency

Kühnen

Wabitsch

Schnurbein

et al. 2022

Orphanet J Rare Dis

View full text Add to dashboard Cite

Introduction Individuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL). Methods Two pivotal Phase 3 trials explored the effect of setmelanotide on body weight and hunger in individuals with obesity due to POMC (NCT02896192) or LEPR (NCT03287960) deficiency. QOL and depression were investigated in parallel using the disease-specific, age-appropriate Impact of Weight on Quality of Life-Lite (IWQOL-Lite), Pediatric Quality of Life Inventory (PedsQL), and Patient Health Questionnaire-9 (PHQ-9). Results In total, the POMC and LEPR trials enrolled 21 patients. Adults (≥ 18 years old; n = 7) had moderate-to-severe impairment in QOL at baseline, with mean (standard deviation [SD]) IWQOL-Lite total score 60.3 (13.2; maximum IWQOL-Lite total score = 100). The effect of setmelanotide on IWQOL-Lite total score was observed as soon as Week 5. Among those with scores at Week 52, 5 of 6 adults experienced a clinically meaningful improvement, with mean (SD) total scores increased from baseline by 24.2 (12.1) points. Children (6–12 years old; n = 2) and adolescents (13–17 years old; n = 4) had impaired QOL at baseline, with mean (SD) self-reported PedsQL total scores 53.3 (6.2) and 63.3 (29.1), respectively (maximum PedsQL total score = 100). Three of 5 patients experienced clinically meaningful improvement in PedsQL, with 2 children whose PedsQL total score increased by 28.3 and 3.3 points and 3 adolescents whose mean (SD) total score increased from baseline by 5.8 (18.3) points. Baseline mean (SD) PHQ-9 score (in those ≥ 12 years old) was 5.3 (3.8) and was generally maintained through Week 52. Conclusions Patients with POMC or LEPR deficiency had impaired, and in some cases severely impaired, QOL before setmelanotide treatment. Setmelanotide improved QOL in patients as early as Week 5, with some patients no longer experiencing impaired QOL at Week 52. Improvements in QOL may be related to a reduction in hunger and body weight associated with setmelanotide. Because of the highly complex psychological consequences of rare genetic diseases of obesity, some patients may require a long period of treatment to improve QOL and benefit from interdisciplinary care.

show abstract

“…A subset of the authors (AG, KC, ET) was involved in a larger evidence generation effort on lipodystrophy and leptin replacement therapy. The list of symptoms of lipodystrophy and associated disease attributes that were included in the interview guide used in this study was originally generated to inform a discrete choice experiment designed to quantify the quality-of-life consequences of lipodystrophy disease attributes recorded in medical chart data of a cohort of 112 patients with generalized lipodystrophy (GL) and partial lipodystrophy (PL) who were treated with leptin replacement therapy at the US National Institutes of Health (NIH) [ 15 ]. The list of symptoms of lipodystrophy and associated disease attributes was reviewed and confirmed by NIH clinical experts who supported the discrete choice experiment study.…”

Section: Methodsmentioning

confidence: 99%

Experiences and Perspectives of Patients with Non-HIV-Associated Lipodystrophies and Their Caregivers: A Qualitative Study

Gomes

Cook

Wong

et al. 2021

Patient

Self Cite

View full text Add to dashboard Cite

Background Lipodystrophy comprises a group of conditions characterized by loss of functional adipose tissue, resulting in severe metabolic complications and a complex range of symptoms. Objective This study sought to gain a holistic understanding of the impact of congenital or non-human immunodeficiency virus acquired lipodystrophies on the quality of life of patients and their caregivers and to capture the impact of lipodystrophy on quality of life using a standard instrument. Methods Ten patients with lipodystrophies and five caregivers from the USA and UK were recruited through convenience sampling and interviewed using a semi-structured questionnaire containing open-ended questions about disease symptoms and attributes and numerical rating scales to prompt discussion of symptom prevalence and impact. After the interview, participants filled out the 36-Item Short Form (SF-36) survey instrument. Conventional conceptual content analysis methods were used to analyze the anonymized transcripts. Results Four concepts were developed: diagnostic journey and symptom management, burden of disease, healthcare resource utilization, and support and advocacy. Participants described lengthy diagnostic journeys and frequent interactions with healthcare systems. Many participants became experts on lipodystrophy through the diagnostic journey and described difficulties accessing effective treatment, even after diagnosis. Both patients and caregivers emphasized the ongoing burden of living with lipodystrophy and the accompanying sense of isolation. Participants turned to disease-specific support groups to cope, engaging in knowledge sharing with other patients and caregivers and developing friendships based on shared experiences. Ten participants completed the SF-36, with a mean (standard deviation) SF-36 score of 0.6 (0.2). Conclusions Currently, there are no qualitative studies that describe the experiences of patients with lipodystrophy and their caregivers. While additional research is needed, educational work like this study is a promising first step that could lead to early diagnosis and access to treatment and support. Supplementary Information The online version contains supplementary material available at 10.1007/s40271-021-00511-5.

show abstract

Effects of Metreleptin on Patient Outcomes and Quality of Life in Generalized and Partial Lipodystrophy

Cited by 25 publications

References 56 publications

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency

Experiences and Perspectives of Patients with Non-HIV-Associated Lipodystrophies and Their Caregivers: A Qualitative Study

Contact Info

Product

Resources

About