The long-acting C5 inhibitor, ravulizumab, is effective and safe in pediatric patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment
In a phase III single-arm trial, the long-acting C5 inhibitor ravulizumab was effective and safe in complement inhibitor-naive children with atypical hemolytic uremic syndrome, with most patients achieving a complete thrombotic microangiopathy response and improved kidney function while allowing extended dosing intervals.
Background
Ravulizumab is a long-acting complement C5 inhibitor engineered from eculizumab that allows maintenance dosing to be extended from every 2-3 weeks to every 4-8 weeks depending on bodyweight. This trial evaluated its efficacy and safety in complement inhibitor-naive children under 18 years of age with atypical hemolytic uremic syndrome (aHUS).
Study design
In this phase III, single-arm trial, ravulizumab was administered every eight weeks in patients weighing 20 kg or more and every four weeks in patients under 20 kg. The primary endpoint was a complete thrombotic microangiopathy (TMA) response, defined as normalization of platelet count and lactate dehydrogenase plus a 25% or greater improvement in serum creatinine, assessed through 26 weeks. Eighteen patients with a median age of 5.2 years were evaluated; at baseline 72.2% had extrarenal symptoms, 38.9% had been in intensive care, and median eGFR was 22 mL/min/1.73 m2.
Key findings
By week 26, 77.8% of patients achieved a complete TMA response, with platelet normalization in 94.4%, lactate dehydrogenase normalization in 88.9%, and a 25% or greater improvement in serum creatinine in 83.3%. By week 50, 94.4% of patients had achieved a complete TMA response. Median platelet count improvement was 246 and 213 x10^9/L through weeks 26 and 50, and median eGFR increased above baseline by 80 and 94 mL/min/1.73 m2, respectively.
Clinical implications
Ravulizumab was effective and safe in treatment-naive pediatric patients with aHUS, producing rapid hematologic normalization and substantial recovery of kidney function. Its extended dosing interval offers a practical advantage over more frequent C5 inhibitor administration in children requiring long-term complement inhibition.
Category
Research
Source
Kidney International
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