#5816 Ravulizumab “De Novo” in Pediatric Patients With Atypical Hemolitic Uremic Syndrome: First Worldwide Cases

Abstract

Background and Aims Ravulizumab is a long-acting C5 inhibitor that has recently demonstrated its effectiveness in adult and pediatric patients for the control of hemolytic uremic syndrome compared to eculizumab, allowing average annual infusion times of up to 70% less. There is still little evidence in the literature of naïve treatment with this drug in pediatrics. Method We present the first two pediatric cases worldwide with the use of de novo Ravulizumab: the first one in the onset of the disease and the second one, post-kidney transplant Results 13-year-old girl referred from another country with 1 week history of acute gastroenteritis with bloody stools, vomiting and compromise of consciousness. Deterioration of general condition, with laboratory tests compatible with thrombotic microangiopathy (TMA), evolves to anuria and convulsive episode requiring invasive mechanical ventilation, corticosteroid boluses, 6 plasmapheresis sessions and 4 intermittent hemodialysis. One Eculizumab dose (600 mg) was administered in the center of origin and STEC was isolated. At admission presented compromised renal function (AKI III), hemolytic anemia, thrombocytopenia, normal ADAMTS-13, negative direct Coombs and decreased complement. Brain MRI study shows images compatible with multiple foci of necrosis. Due to the persistent requirement of renal replacement therapy and persistent TMA, Ravulizumab was started with a loading dose (2400 mg) and a second dose after 2 weeks. The need for renal replacement therapy ceased with improvement of hemolysis and renal function. Genetic study showed mutation of uncertain significance in heterozygosis in exon 6 (c.881_883, p.Ala292del) with risk polymorphism for HUSa (deletion CFHR3-CFHR1) Case 2: 7-year-old girl (stage 5 CKD) in chronic hemodialysis 3 times/week secondary to aHUS (CD46 mutation) was admitted for kidney transplant from a living donor (father), performing hemodialysis session before surgical intervention. Low-intermediate immunological risk (PRA 0%, 9 HLA matches) and high CMV infectious risk (valganciclovir prophylaxis). Induction treatment: Basiliximab, tacrolimus, mycophenolate and steroids. First dose of Ravulizumab was infused the day before transplantation (900mg), well tolerated. 36 hours after presented acute pulmonary edema as well as a drop in hemoglobin (4g/dL). With normal laboratory hemolysis parameters, urgent abdominal-pelvic CT was performed due to suspicion of bleeding, confirming an active bleeding. Surgical reintervention was decided due to ureteral bleeding and the tunnel was redone with good results. The patient has had a favorable evolution of renal function, with a normal value of creatinine at discharge (0.43 mg/dl). Protein/Creatinine urine ratio (iPr/Cr) increases to a maximum of 8 mg/mg. Negative DSA levels but the option of renal biopsy was assessed and ruled out due to a decrease in proteinuria (iPr/Cr 0.51 mg/mg). She received second dose of ravulizumab after 2 weeks, remain stable with no data on recurrence of her underlying disease today. Conclusión: In the two patients, the initial treatment with Ravulizumab was satisfactory, both in the acute phase of the disease and in the immediate post-transplantation. In the first case we observed a functional recovery from the first dose with no notable adverse effects up today, as in the post-transplant patient, maintaining a good control of TMA despite more spaced dosing (8 weeks). The inclusion of this drug in the therapeutic arsenal opens a new safe treatment route in pediatric patients with HUSa