OC11.2 - ECE_2967 - Metreleptin therapy in pediatric and adult patients with congenital leptin deficiency: a multicenter real-world experience
Bildiriler > Özet Bildiri
Yazarlar: Selin Uzun Karaüzüm, Sevde Nur Firat, Funda Feryal Taş, Gökçen Güngör Semİz, Leyla Akın, Elif Özsu, Mehmet Nuri Özbek, Zafer Pekkolay, Hüseyin Onay, Elif Oral, Baris Akinci, Samim ÖZEN
European Journal of Endocrinology, , , Uluslararası, Özet Bildiri, Wos, cilt 195
DOI: 10.1093/ejendo/lvag096.137
Özet
Abstract Background Congenital leptin deficiency (CLD) is a rare monogenic cause of severe early-onset obesity and hyperphagia, with limited long-term real-world evidence on metreleptin therapy. In this study, we aimed to evaluate the long-term clinical outcomes and safety of metreleptin therapy in a large, multicenter cohort of pediatric and adult patients. Methods We conducted a multicenter, observational cohort study including 17 patients with CLD (10 pediatric, 7 adult) across 8 centers. Clinical characteristics, genetic findings, longitudinal anthropometric measurements, metabolic parameters, and total daily metreleptin doses were systematically evaluated. Pediatric and adult cohorts were analyzed separately to account for age- and growth-related trajectories. Repeated-measures analyses were performed in subgroups with complete longitudinal data. One patient who developed loss of efficacy due to neutralizing antibodies was presented separately. Results Obesity onset clustered within the first year of life in 87.5% of patients, and hyperphagia was present in all patients at baseline. Pathogenic or likely pathogenic LEP gene variants were identified in most cases; three individuals with ongoing genetic analyses were included based on markedly low leptin levels and a robust clinical response to metreleptin. Across the entire cohort, metreleptin induced a marked, time-dependent reduction in BMI (median −25.7% at month 6; −40.7% at month 18). In pediatric patients, BMI and BMI SDS decreased substantially (mean BMI SDS 5.52 ± 1.47 at baseline to 2.66 ± 1.37 by month 24) and remained stable long term; all children showed a net BMI SDS reduction at last follow-up. Linear growth was preserved, with stable height SDS and no evidence of growth attenuation. In adults, BMI decreased from 55.7 kg/m2 at baseline to 29.9 kg/m2 by month 18, with subsequent inter-individual variability but overall preservation of therapeutic gains. Glycemic and lipid parameters remained largely within reference ranges, no severe adverse events occurred, and total metreleptin doses remained stable without systematic escalation. A boy with a large deletion in the LEP gene started metreleptin at 24 months and initially lost 10 kg. By month 6, he began regaining weight and developed injection-site reactions. He tested strongly positive for neutralizing antibodies and was later treated with an investigational agent. Conclusions This multicenter cohort is among the largest real-world series jointly evaluating pediatric and adult patients with congenital leptin deficiency. Metreleptin was effective and well-tolerated during long-term follow-up in routine clinical practice. Neutralizing antibody–associated loss of efficacy occurred in one patient; otherwise, responses were sustained without clinically relevant safety signals.