Complement Inhibitors for Atypical Hemolytic Uremic Syndrome and the Role of the Pharmacist

Atypical hemolytic uremic syndrome (aHUS) is a very rare disease state that causes thrombi in the small blood vessels, blocking blood flow and resulting in end-organ dysfunction. As a result, patients may experience hemolytic anemia, thrombocytopenia, and acute kidney failure. Since aHUS has a poor prognosis, it is essential that diagnosis occurs rapidly, and treatment is started as soon as possible to prevent progression to endstage renal disease (ESRD).

Kathryn Dane, PharmD, BCPS, recently provided an update on available therapies for the management of aHUS at the 2020 National Association of Specialty Pharmacy Annual Meeting. In order to treat patients appropriately, Dane emphasized the importance of distinguishing aHUS from thrombotic thrombocytopenia purpura, as they have very similar clinical presentations, but pathophysiology and treatment vary significantly.

Before the development of C5 inhibitors, treatment for aHUS was limited to plasma infusion with or without plasma exchange. Although these treatments are beneficial, approximately 50% to 66% of patients still die or progress to ESRD. Dane explained, “The development of C5 inhibitors drastically changed outcomes for patients with aHUS, with approximately 80% of patients requiring hemodialysis at the time of treatment initiation experiencing improved renal function and discontinuation of hemodialysis with C5 inhibitor administration.” Also, earlier initiation of C5 inhibitors is associated with an increased likelihood of renal recovery.

Two C5 inhibitors, eculizumab and ravulizumab, are FDA approved in adults and children for treatment of aHUS. Both agents are administered via intravenous (IV) infusion. The C5 inhibitor ravulizumab, approved in 2019, is a reengineered, pegylated version of eculizumab developed to extend the agent’s half-life (51.8 days), allowing maintenance doses to be administered every 4 or 8 weeks. In addition to dosing considerations for both agents, transitioning from eculizumab to ravulizumab was reviewed.

Dane emphasized that C5 inhibitors have a boxed warning for meningococcal infections. Therefore, patients should be immunized according to the Advisory Committee on Immunization Practices (ACIP) guidelines for both MenACWY and MenB. Antimicrobial prophylaxis against Neisseria meningitidis is required for a minimum of 2 weeks after vaccination and potentially longer, as breakthrough infections have been reported despite appropriate vaccination.

Dane then discussed the integral role that specialty and infusion pharmacists can play in managing patients by assisting with dosing of therapies and ensuring all immunizations are current. To highlight the additional roles of pharmacists, videos were integrated throughout the activity featuring the preparation and administration of eculizumab and ravulizumab, information on the Risk Evaluation and Mitigation Strategy (REMS) program, and a pharmacist counseling a patient with aHUS. The presentation ended with future directions, including the investigational use of once-weekly subcutaneous administration of ravulizumab, as well as other C5 inhibitors in phase 2 trials that may continue to increase the potential therapeutic options for patients with aHUS.

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