Sistema de Salut de Catalunya
Institut Català de la Salut
[Nester CM] Stead Family Children’s Hospital-University of Iowa, Iowa City, Iowa, USA. [Eisenberger U] Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. [Karras A] Hôpital Européen Georges Pompidou, Paris, Île-de-France, France. [le Quintrec M] Service de Néphrologie et Transplantation Rénale, Centre Hospitalier Universitaire de Montpellier, Montpellier, France. [Lightstone L] Department of Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, UK. Imperial College Renal and Transplant Centre, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK. [Praga M] Department of Medicine, Complutense University, Hospital Universitario 12 de Octubre, Madrid, Spain. [Soler MJ] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-03-21T09:48:15Z
2025-03-21T09:48:15Z
2024
2025-02
C3 glomerulopathy; Iptacopan; Transplantation
Glomerulopatia C3; Iptacopan; Trasplantament
Glomerulopatía C3; Iptacopan; Trasplante
Introduction C3 glomerulopathy (C3G) is a complex, chronic, ultra rare, progressive primary glomerulonephritis, resulting from alternative complement pathway overactivation, leading to kidney failure in most patients, and frequent recurrence in transplants. Iptacopan (LNP023) is an oral, proximal complement inhibitor specifically targeting factor B, that selectively inhibits the alternative complement pathway. Methods This was a phase 2 extension study of 26 adult patients with native kidney (cohort A), or recurrent C3G (post kidney transplantation; cohort B) receiving open label iptacopan. Results At 12 months, patients in cohort A had a significant reduction in 24-hour urine protein-to-creatinine ratio (UPCR; 57%; P < 0.0001; confidence interval [CI]: 0.31–0.59), an improvement in estimated glomerular filtration rate (eGFR; 6.83 ml/min per 1.73 m2; P = 0.0174; CI: 1.25–12.40), and an increase in serum C3 levels (geometric mean ratio to baseline: 3.53; P < 0.0001; CI: 3.01–4.15). In cohort B, most patients had normal urinary protein excretion at baseline (mean [range] 24-hour UPCR: 121 [9–445]), which was slightly lower by 12 months (21% reduction; CI: 0.48–1.31; P = 0.3151). In cohort B at 12 months, mean eGFR was at baseline values (mean change from baseline: −0.96 ml/min per 1.73 m2; P = 0.7335; CI: −6.60 to 4.69). Cohort B patients had significantly higher serum C3 values at 12 months compared with baseline (ratio:1.96; CI: 1.70–2.27; P < 0.0001). In cohorts A + B combined, the median difference in C3 deposit score on renal biopsy from baseline was −7.00 (CI: −12.00 to 4.00;) at 9 to 12 months treatment with iptacopan. Conclusion These data provide a clinical rationale for further evaluation of long-term treatment of C3G with iptacopan.
This study was funded by Novartis Pharma AG.
Article
Published version
English
Glomerulonefritis - Tractament; Medicaments immunosupressors - Ús terapèutic; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive Agents::Complement Inactivating Agents; Other subheadings::Other subheadings::/therapeutic use; DISEASES::Immune System Diseases::Glomerulonephritis, Membranoproliferative; Other subheadings::Other subheadings::Other subheadings::/drug therapy; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::factores inmunitarios::inmunosupresores::inactivadores del complemento; Otros calificadores::Otros calificadores::/uso terapéutico; ENFERMEDADES::enfermedades del sistema inmune::glomerulonefritis membranoproliferativa; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
Elsevier
Kidney International Reports;10(2)
https://doi.org/10.1016/j.ekir.2024.10.023
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3439]
