Blockade of the Terminal Complement Cascade Using Ravulizumab in a Pediatric Patient With Anti-complement Factor H Autoantibody-Associated aHUS: A Case Report and Literature Review

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare disease in pediatrics with 6-10% of cases associated with complement factor H autoantibodies . Ravulizumab is a new treatment option available for long-term management through blockage of the terminal complement cascade. We report a case of a previously healthy eight-year-old female who presented with hemolytic anemia, thrombocytopenia, and acute kidney injury. Low complement C3, normal ADAMTS13, and negative rheumatology and infectious disease panels suggested aHUS. A follow-up complement aHUS/TMA gene panel was negative for ADAMTS13, C3, CD46, CFB, CFD, CFH, CFHR1, CFHR3, CFHR5, CRI, DGKE, PLG, and THBD mutations and positive for MCP/CD46 haplotype and CFH-H3 haplotype. Further testing found decreased factor H (B1H) plasma level and increased factor H autoantibody, suggesting anti-factor H antibody-associated aHUS. She received hemodialysis (2 treatments) and eculizumab was initiated promptly. The patient had complete renal recovery after one month of therapy, and anemia, thrombocytopenia, and hemolysis resolved after two months of therapy. After five months of therapy, eculizumab was successfully switched to ravulizumab. After 12 months of initial diagnosis, complement C3 and factor H normalized, however, factor H autoantibody remained elevated. The case supports the notion that timely recognition of anti-FH-associated aHUS is important for disease management and that early specific therapy with immunosuppression results in favorable outcomes. It also illustrates that the blockade of the terminal complement cascade using eculizumab holds promise for pediatric cases. Finally, eculizumab can be safely switched to ravulizumab with an optimal longer duration between treatments in the context of aHUS.

Atypical Hemolytic Uremic Syndrome Treated With Ravulizumab or Eculizumab: A Claims-Based Evaluation of Health Care Resource Utilization and Clinical Outcomes in the United States

“…These data thereby provide a valuable contribution to the understanding of real-world treatment patterns for ravulizumab, given that the real-world evidence for ravulizumab is currently limited to case reports and case series. 26 , 27 , 28 , 29 , 30 In this study, there were few treatment-switch patients with claims for aHUS-related clinical procedures at all time points, potentially because of disease stabilization during the eculizumab treatment before switching the treatment to ravulizumab, and there were fewer health care facility and home visits and lower medical costs during the postindex versus the preindex period. In addition, fewer patients who switched treatment reported claims for clinical manifestations over the postindex versus preindex period.…”