POW: Paper of the week


Effect of Leptin Therapy on Survival in Generalized and Partial Lipodystrophy: A Matched Cohort Analysis

This week, Keziah Cook et al. publish in the Journal of Clinical Endocrinology and Metabolism a study on the treatment effect of metreleptin on survival in patients with generalized (GL) and partial lipodystrophy (PL), excluding non-HIV-related lipodystrophy. Kaplan-Meier survival analysis was used to estimate mean time to mortality from treatment initiation for metreleptin-treated patients and from the index observation date for matched metreleptin-naïve patients. A Cox proportional hazards model was used to estimate the differences in risk of mortality between the two cohorts as a hazard ratio and to model survival probability over time. In the metreleptin-treated cohort, there were 11 deaths among patients with GL (7 with congenital generalized lipodystrophy [CGL]; 4 with acquired generalized lipodystrophy [AGL]) and 1 death among patients with PL (patient had familial partial lipodystrophy [FPLD]). In the matched metreleptin-naïve cohort, there were 9 deaths among patients with GL (all CGL) and 3 deaths among patients with PL (all FPLD). The most frequently reported causes of death as recorded in patient records were heart, liver and/or kidney disease, or infections. Kaplan-Meier analysis did not reveal a statistically significant difference in time-to-mortality between metreleptin-treated patients when compared to matched metreleptin-naïve patients. However, results of a Cox proportional hazards model showed that after adjusting for other covariates (i.e., lipodystrophy diagnosis, birth year, triglyceride levels, elevated HbA1c, ≥ 1 episode of pancreatitis, and the presence of observed abnormalities in the heart or kidneys), metreleptin treatment was associated with a 65% reduction in mortality risk (HR 0.348, 95% CI: 0.134-0.900; P = 0.029).  However, significant differences in mortality risk and time-to-mortality between metreleptin- treated and metreleptin-naïve patients in the GL subgroup were not detected from the Kaplan-Meier analysis or Cox proportional hazards model. The Cox model was not powered to detect differences in mortality risk in subgroups of patients with AGL or CGL. In fact, the authors stated that “A larger sample size is needed to reliably assess the effect of metreleptin therapy on mortality risk in the GL subgroup, where a non-significant trend towards lower mortality was observed, as well as in subgroups of specific GL and PL subtypes”.