Sex: U
Vaccine: COVID19, FLUX
Symptoms: Blood lactate dehydrogenase, Breakthrough haemolysis, Protein C
Clinical narrative: Breakthrough hemolysis (BTH); This literature case was received on 04-Dec-2023 and concerned a patient of unreported age and gender.   The aim of this study was to assess the safety of switching from high-dose eculizumab to approved, weight-based ravulizumab.  This Study was an ongoing study, single-arm, multicenter trial designed to investigate the impact of switching treatment from fixed, high-dose IV eculizumab (1200 mgq2w) to weight-based IV ravulizumab q8w in adult (= 18 years of age; N = 18) patients with PNH. Prior to (= three months) screening, patients received high-dose IV eculizumab (1200 mg q2w); patients continued to receive this throughout the three-month screening period before switching to weight-based IV ravulizumab. The primary endpoint was the proportion of patients who experienced serum free C5-associated breakthrough hemolysis (BTH). Other endpoints included change in free C5 concentrations and LDH levels over time, and the proportion of patients with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)   The patient's concurrent condition included paroxysmal nocturnal hemoglobinuria (PNH). The patient's historical drug included eculizumab used for paroxysmal nocturnal hemoglobinuria (PNH). The patient's concomitant medications included ravulizumab used for paroxysmal nocturnal hemoglobinuria (PNH).  On an unspecified date, the patient was vaccinated with influenza vaccine (brand not specified; dose, anatomical location, route of administration and indication: not reported). The batch number was not reported.  On the same date, the patient was vaccinated with COVID-19 vaccine (brand not specified; dose, anatomical location, route of administration and indication: not reported). The batch number was not reported.  On an unspecified date, one day after receiving the influenza vaccine, and non-company co-suspect COVID-19 vaccine, the patient experienced breakthrough hemolysis (BTH). Laboratory test showed lactate dehydrogenase increased (LDH level) with result 492.0 U/L (normal reference ranges: 120.0-246.0 U/L).     On an unspecified date, reported as four days after the event, free C5 level was detected with result of 0.11 µg/mL. The patient continued ravulizumab treatment.   The outcome of the event was not reported.   The reporter did not provide a causality assessment. However, the reporter stated that the event was deemed to be vaccine-related as both coronavirus disease 2019 and influenza vaccinations were administered the day prior to the event.  From results, from baseline to day 183, no instances of free C5-associated BTH were reported and free C5 concentrations remained below 0.5 µg/mL for all patients at all study timepoints. Similarly, from baseline to day 183, LDH levels remained = 1.5 × ULN in all patients. Up to day 183, 7/10 patients (70.0%) reported TEAEs that were mild (n =3, 30.0%) or moderate (n = 4, 40.0%) in severity. There were no instances of meningococcalinfection, TESAEs and none of the documented TEAEs led to death or study withdrawal  In conclusion, results of this interim analysis showed that, based on a small sample of patients with PNH (N = 10), switching treatment from high-dose IV eculizumab (1200 mg q2w) to standard, weight-based IV ravulizumab q8w was well tolerated, with minimal changes in laboratory measures associated with PNH symptoms. Up to day 183, no free C5-associated BTH was reported and the safety profile of ravulizumab was considered comparable to previously published studies, with no instances of meningococcal infection or TESAEs reported.   The event of breakthrough hemolysis was considered to be medically significant by Physician.   Company comment: The aim of this study was to assess the safety of switching from high-dose eculizumab to approved, weight-based ravulizumab. A patient of unreported age developed breakthrough haemolysis one day after receiving the suspect product influenza vaccine, and non-company co-suspect COVID-19 vaccine. Laboratory test showed lactate dehydrogenase increase. The patient's significant concurrent condition included paroxysmal nocturnal hemoglobinuria. Despite confounding by co-suspect vaccine, causal role of the suspect product cannot be excluded. Therefore, causality for the reported events is assessed as possibly related due to plausible temporal relationship.; Sender's Comments: The aim of this study was to assess the safety of switching from high-dose eculizumab to approved, weight-based ravulizumab. A patient of unreported age developed breakthrough haemolysis one day after receiving the suspect product influenza vaccine, and non-company co-suspect COVID-19 vaccine. Laboratory test showed lactate dehydrogenase increase. The patient's significant concurrent condition included paroxysmal nocturnal hemoglobinuria. Despite confounding by co-suspect vaccine, causal role of the suspect product cannot be excluded. Therefore, causality for the reported events is assessed as possibly related due to plausible temporal relationship.