Eculizumab as first-line treatment for patients with severe presentation of complement factor H antibody–mediated hemolytic uremic syndrome

• Published in: Pediatric nephrology (Berlin, West) Vol. 40; no. 4; pp. 1041 - 1047
• Main Authors: Coccia, Paula A., Alconcher, Laura F., Ferraris, Veronica, Lucarelli, Lucas I., Grillo, Maria A., Arias, Maria Andrea, Saurit, Mariana, Ratto, Viviana M., dos Santos, Celia, Sánchez-Luceros, Analía
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2025; Springer Nature B.V
• Subjects: Antibodies; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Apheresis; Child; Children; Complement factor H; Complement Factor H - immunology; Complement Inactivating Agents - therapeutic use; Complement system; Dialysis; Female; Hemolytic uremic syndrome; Hemolytic-Uremic Syndrome - blood; Hemolytic-Uremic Syndrome - diagnosis; Hemolytic-Uremic Syndrome - drug therapy; Hemolytic-Uremic Syndrome - immunology; Humans; Immunosuppression; Immunosuppressive agents; Immunosuppressive Agents - therapeutic use; Immunotherapy; Kidney diseases; Male; Medicine; Medicine & Public Health; Monoclonal antibodies; Mycophenolate mofetil; Mycophenolic acid; Nephrology; Original Article; Pediatrics; Plasmapheresis; Prednisone; Renal Dialysis; Retrospective Studies; Rituximab; Thrombotic microangiopathy; Treatment Outcome; Urology; Eculizumab; Thrombotic microangiopathy; Complement factor H; Atypical HUS; Anti-factor H antibodies; Complement-mediated HUS
• ISSN: 0931-041X; 1432-198X; 1432-198X
• DOI: 10.1007/s00467-024-06530-2

    Background Complement factor H (FH) antibody–mediated hemolytic uremic syndrome (HUS) has varying prevalence globally. Plasmapheresis and immunosuppressive drugs are the standard treatment. Recently, eculizumab has been reported as an effective alternative. This study aims to report four children with FH antibody–mediated HUS managed with eculizumab plus immunosuppression as first-line therapy. Methods A retrospective chart review was conducted for children aged ≤ 18 years old with complement-mediated HUS in two referral centers. Patients with FH antibody–mediated HUS treated with eculizumab as first-line therapy were included. Results Four children (aged 6–11 years old) were included. Dialysis was necessary in three patients. Eculizumab was administered 5–23 days after onset. None of them received plasmapheresis. Prednisone and mycophenolate mofetil were added after receiving positive FH antibody results. Hematological signs and kidney function improved after the second eculizumab dose. Eculizumab was discontinued in three patients after 6 months. One patient required rituximab due to persistent high FH antibody titers; discontinuation of eculizumab occurred after 15 months without recurrence. No treatment-related complications were observed. During a mean 12-month follow-up (range 6–24 months), no relapses were recorded and all patients ended with normal GFR. Conclusion Our data suggest that a short course of 6 months of C5 inhibitor might be sufficient to reverse thrombotic microangiopathy symptoms and improve kidney function in patients with severe FH antibody–mediated HUS. Simultaneously, adding immunosuppressive agents might reduce the risk of relapse and allow cessation of C5 inhibition in a shorter period of time. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information