Eculizumab Is an Effective Treatment for Atypical Hemolytic Uremic Syndrome in Pediatric and Adult Patients with or without Identified Genetic Complement Mutations or Complement Factor H Autoantibodies

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare, chronic disorder characterized by uncontrolled complement activation that results in life-threatening systemic thrombotic microangiopathy (TMA). Up to 79% of aHUS patients (pts) will have permanent renal damage, progress to end-stage renal disease, or die within 3 years following a clinical manifestation. Genetic abnormalities have been identified in up to 70% of pts with aHUS. Eculizumab (ECU) has previously been shown to be highly effective in the treatment of aHUS in 2 controlled, prospective studies (pts aged ≥12 y), and 1 retrospective study (pts aged <18 y). The purpose of this analysis was to evaluate the efficacy of ECU in adult and pediatric aHUS pts with or without identified genetic abnormalities in 2 additional prospective studies.

Methods: This was a post hoc subgroup analysis of efficacy outcomes after 26 weeks based on the presence or absence of identified genetic abnormalities – mutations, complement factor H (CFH) autoantibodies, or polymorphisms – in 2 prospective studies conducted in either pediatric (<18 y) or adult pts (≥18 y) with aHUS.

Results: In the pediatric and adult trials, respectively, 50% and 49% of pts had no identified genetic complement mutation or detectable CFH autoantibodies. There were no significant differences in demographics or baseline characteristics of pts with or without genetic abnormalities in either trial. ECU led to significant improvements in hematologic and renal outcomes regardless of mutation/CFH autoantibody status (Table). The change from baseline in platelet count and estimated glomerular filtration rate (eGFR) was statistically significant in mutation and no-mutation groups in both trials. In addition, of the pts in the mutation groups who were receiving PE/PI at baseline, 100% (6/6) of pediatric pts and 83.3% (15/18) of adult pts discontinued PE/PI after initiating ECU. In pts without an identified mutation on plasma exchange/plasma infusion (PE/PI) at baseline, 75% (3/4) of pediatric pts and 64.7% (11/17) of adult pts also discontinued PE/PI. For pts on dialysis at baseline in the mutation groups, 100% (5/5) of pediatric and 78.6% (11/14) of adult pts discontinued dialysis by 26 weeks, as did 66.7% (4/6) of pediatric and 90% (9/10) of adult pts in the no-mutation groups, respectively.

Conclusions: Our analysis shows that significant improvements in hematological and renal outcomes, and rates of discontinuation of dialysis and PE/PI, occur in both pediatric and adult pts regardless of the presence or absence of identified complement abnormalities. Given that genetic testing can take several months to complete and that the absence of an identified mutation, CFH autoantibodies, or polymorphisms does not rule out aHUS, our results provide additional evidence for initiating ECU upon clinical diagnosis of aHUS, without the availability of genetic testing results.

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