Naslov
Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency

Autori
Burton, Barbara K. ; Sanchez, Alejandra Consuelo ; Kostyleva, Maria ; Martins, Ana Maria ; Marulkar, Sachin ; Abel, Florian ; Barić, Ivo

Izvornik
Journal of pediatric gastroenterology and nutrition (0277-2116) 74 (2022), 6; 757-764

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
cirrhosis dyslipidemia lipid metabolism disorders lysosomal storage diseases transaminases

Sažetak
Bjectives: Sebelipase alfa is approved for treatment of lysosomal acid lipase deficiency (LAL-D). This single-arm, open-label study (NCT02112994) evaluated sebelipase alfa efficacy and safety in patients with LAL-D. Methods: Patients >8 months of age diagnosed with LAL-D received sebelipase alfa 1.0 mg/kg by intravenous infusion every other week (qow) for up to 144 weeks. Dose escalation to 3.0 mg/kg qow and subsequently to 3.0 mg/kg weekly was permitted, per protocol ; dose reductions for tolerability were permitted to 0.35 mg/kg qow. Descriptive statistical analyses were conducted. Results: Thirty-one patients were enrolled and treated. Baseline median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were 63.5 and 65.5 U/L, respectively. Twenty-eight patients completed 96 weeks of treatment, and 25 continued into the extended treatment period ; 19 completed 144 weeks. From baseline to week 144, median ALT and AST levels changed by −42.0 and −22.0 U/L, respectively, median liver and spleen volumes changed from 1.4 to 1.3 and from 2.6 to 2.3 multiples of normal, respectively, median low- density lipoprotein cholesterol levels decreased by 52.6 mg/dL, and median high-density lipoprotein cholesterol increased by 9.8 mg/dL. Liver biopsies showed mostly improved or stable histopathology at 48 and 96 weeks versus baseline. Infusion- associated reactions were mild (n = 1) or moderate (n = 2). One patient (a candidate for liver transplant at baseline) discontinued treatment because of liver transplant (unrelated to treatment). Two patients tested positive for nonneutralizing, anti-drug antibodies on 1 occasion each. Conclusion: Sebelipase alfa was well tolerated and resulted in sustained improvements in liver and lipid parameters.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA