Case Report: Atypical HUS Presenting With Acute Rhabdomyolysis Highlights the Need for Individualized Eculizumab Dosing

Abstract

BackgroundAtypical hemolytic uremic syndrome (aHUS) is an ultra-rare orphan disease caused by dysregulated complement activation resulting in thrombotic microangiopathy. Although complement-mediated endothelial injury predominantly affects the renal microvasculature, extra-renal manifestations are present in a significant proportion of patients. While eculizumab has significantly improved the morbidity and mortality of this rare disease, optimizing therapeutic regimens of this highly expensive drug remains an active area of research in the treatment of aHUS.Case PresentationThis report describes the case of a previously healthy 4 year-old male who presented with rhabdomyolysis preceding the development of aHUS with anuric kidney injury requiring dialysis. Clinical stabilization required increased and more frequent eculizumab doses compared with the standardized weight-based guidelines. In the maintenance phase of his disease, pharmacokinetic analysis indicated adequate eculizumab levels could be maintained with an individualized dosing regimen every 3 weeks, as opposed to standard 2 week dosing, confirmed in this patient over a 4 year follow up period. Cost analyses show that weight-based maintenance dosing costs $312,000 per year, while extending the dosing interval to every 3 weeks would cost $208,000, a savings of $104,000 per year, relative to the cost of $72,000 from more frequent eculizumab dosing during his initial hospitalization to suppress his acute disease.ConclusionThis case exemplifies the potential of severe, multisystem involvement of aHUS presenting with extra-renal manifestations, including rhabdomyolysis as in this case, and highlights the possibility for improved clinical outcomes and higher value care with individualized eculizumab dosing in patients over the course of their disease.

Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis

“…For example, eculizumab is currently registered only as interval therapy for secondary prophylaxis against acute exacerbations of NMOSD. However, this compound is in off-label use in acute phases of haemolytic-uraemic syndrome 37 among other diseases that go along with acute complement factor 5 (C5) activation and may also be a therapeutic option in patients with NMOSD with acute exacerbations when PEX provides only limited or no benefit. 38 Here, GAM composites may be a valuable biomarker for therapeutic decision making, on the background of the enormous costs of anti-C5-antibody therapies.…”