5PSQ-128 Case report: adverse reaction following intraviteal administration of aflibercept

<h3>Background and Importance</h3> Atypical haemolytic uremic syndrome (aHUS) is a rare disease characterised by a classic triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. Its diagnosis is made using exclusion criteria, as it can be easily confused with other microangiopathic disorders, such as thrombotic thrombocytopenic purpura (TTP), for which the activity of the enzyme ADAMTS13 is evaluated, and typical HUS, which is usually caused by the Shiga toxin of Escherichia coli. <h3>Aim and Objectives</h3> In this particular case, aHUS was triggered after the first administration of aflibercept, an antiangiogenic drug, and, in addition, the patient had positive re-exposure after the second dose. Aflibercept is primarily used for the treatment of age-related macular degeneration (AMD) by intravitreal injections and as part of the FOLFIRI scheme in oncology. However, the main problem in this case lay in the lack of understanding of the pharmacokinetics when administered intravitreally. Although administration is local, aflibercept can be absorbed systemically, inhibiting vascular endothelial growth factor (VEGF) and triggering adverse effects such as aHUS. <h3>Material and Methods</h3> The patient underwent the pertinent tests to rule out thrombotic thrombocytopenic purpura (TTP), obtaining a negative result in the ADAMTS13 test, as well as for Shiga toxin, which was negative after the nucleotide amplification test. Biochemical evaluation showed acute renal failure (with elevated serum creatinine: 4,75 mg/dL), thrombocytopenia (102,000 platelets per microlitre of blood), and non-immune haemolytic anaemia (with elevated LDH and haemoglobin levels: 11 g/dL). In addition to these results, the complement factor C3 was analysed (51 mg/dL). <h3>Results</h3> After both episodes, eculizumab, the treatment of choice, was administered to reverse the condition and promote recovery from the adverse event, resulting in a positive response after the first administration. However, re-exposure to aflibercept triggered a more severe episode, necessitating prolonged patient monitoring, primarily under the supervision of the nephrology team. <h3>Conclusion and Relevance</h3> A review of pharmacovigilance databases such as FEDRA, Eudravigilance, and VigiBase revealed that three cases of aHUS have been reported in connection with the administration of aflibercept. This highlights the importance of monitoring for potential systemic effects of intravitreal treatments, especially in patients who might be predisposed to developing serious complications such as aHUS. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest