Case Report: Benefits and Challenges of Long-term Eculizumab in Atypical Hemolytic Uremic Syndrome

Abstract

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011. The long-term safety and efficacy of this novel drug in the pediatric population remain under review. We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010. She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized. Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment. She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated against invasive meningococcal infection before beginning eculizumab therapy and take appropriate antibiotic prophylaxis during treatment, and we suggest that vaccine responses should be checked and followed annually. Clinicians need to maintain a high index of suspicion for invasive meningococcal disease. Neither vaccination nor antibiotic prophylaxis provides complete protection in patients on eculizumab therapy. The appropriate dosage of eculizumab needed to achieve remission in aHUS in the pediatric population is unknown. Having achieved remission in our patient, we monitor eculizumab and CH50 levels to evaluate ongoing blockade of the terminal complement cascade. Such information may help guide dosing intervals in the future.

High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine

“…Meningococcal disease following MenACWY vaccination in eculizumab recipients has been reported previously ( 1 , 5 ), and in vitro data have shown that eculizumab impairs meningococcal killing in whole blood even in subjects vaccinated against the relevant meningococcal serogroup ( 6 ). In addition, although nongroupable N. meningitidis is often carried asymptomatically in the nasopharynx, it rarely causes disease in healthy persons ( 7 ).…”

Thrombotic Microangiopathy and the Kidney

“…For this reason, meningococcal vaccination is considered mandatory; however, serologic response is variable (39), and the efficacy of vaccination in the context of complement blockade is uncertain (6). Long-term antibiotic prophylaxis is therefore recommended for the duration of treatment and up to 3 months after withdrawal (6), although meningococcal infection can occur despite these precautions (40,41). Thus, patient education regarding vigilance is essential.…”

Long‐term remission with eculizumab in atypical haemolytic uraemic syndrome

“…The long‐term safety of eculizumab is promising yet remains uncertain. Safety has been previously reported in children with aHUS treated for up to 4 years . In patients with paroxysmal nocturnal haemoglobinuria, long‐term safety data are available in excess of 8 years .…”