Rare infection seen in girl, 16, with PNH treated with Empaveli: Report
Case highlights 'obstacles' to treatment posed by meningococcal infections
An unusual meningococcal infection during treatment with Empaveli (pegcetacoplan) was reported in a 16-year-old girl with paroxysmal nocturnal hemoglobinuria (PNH), according to a case report from Finland.
Meningococcal infections are a known risk for patients receiving complement inhibitors, such as Empaveli. As such, patients typically are vaccinated before starting treatment to prevent such infections.
However, despite vaccination, this teen still developed meningococcal sepsis, a severe life-threatening response to infection that may lead to organ damage.
“Our case sheds light on the obstacles involved in both diagnosing and treating [meningococcal] infections in complement inhibitor recipients and demonstrates the importance of vigilance and rapid administration of effective antimicrobial drugs,” the researchers wrote.
The case was described in a study titled “Meningococcal Sepsis in Patient with Paroxysmal Nocturnal Hemoglobinuria during Pegcetacoplan Therapy,” which was published in the journal Emerging Infectious Diseases.
Girl got vaccinated against meningococcal infections before treatment
In most cases, PNH is caused by mutations in the PIGA gene in hematopoietic stem cells — the cells in the bone marrow that are responsible for giving rise to new blood cells. This ultimately lowers the levels of proteins found on the surface of blood cells that normally signal to the immune system that these cells are a healthy part of the body.
Without these proteins, the complement system, a part of the immune system, becomes activated and starts attacking and destroying red blood cells in a process known as hemolysis. This, in turn, leads to PNH symptoms.
Several medications are approved to treat PNH, most of which work by targeting the C5 protein of the complement cascade to block complement activation. However, these therapies may also increase a patient’s risk of developing serious meningococcal infections, caused by the bacteria Neisseria meningitides.
Here, researchers described the case of a teenage girl with aplastic anemia and PNH, who developed meningococcal sepsis during treatment with Empaveli, a complement inhibitor that works by targeting a complement protein called C3. Aplastic anemia, a condition that sometimes accompanies PNH, occurs when the bone marrow is unable to make enough new blood cells.
One year after being diagnosed with PNH and aplastic anemia, the girl started treatment with Ultomiris (ravulizumab), an approved C5 inhibitor, to manage severe hemolysis. She was also vaccinated against meningococcal infections.
7 days of antibiotics successfully treated girl’s infection, per report
A few months following the start of treatment, she switched to Empaveli due to extravascular hemolysis, or red blood cell destruction occurring outside blood vessels. Unlike complement inhibitors that target the C5 protein, which mainly prevent hemolysis inside blood vessels, Empaveli targets C3, helping to stop hemolysis both inside and outside blood vessels.
At a follow-up appointment about one month after switching to Empaveli, blood test results revealed she had low levels of leukocytes, or white blood cells. She subsequently developed signs of septic infection, specificially a headache in the back of the head, a fever of 39.5 C (about 103.1 F), and a fast heart rate.
Further examination indicated she had low levels of hemoglobin, the oxygen-carrying protein in red blood cells, and high levels of lactate dehydrogenase (LDH), a marker of tissue damage that can indicate the presence of several conditions, including infections such as meningococcal infections.
Complement inhibition with [Empaveli] and potential residual [Ultomiris] predisposed this patient to an unusual septic infection by nonencapsulated N. meningitidis, despite immunization.
The girl started treatment with the antibiotic cefuroxime.
In the morning following her hospital admission, her fever peaked at 40.1 C (about 104.2 F), hemoglobin levels decreased, and LDH levels increased, requiring a transfusion of packed red blood cells. She continued treatment with Empaveli, and after the detection of bacteria in her bloodstream, the antibiotic dosage was increased.
Further analysis led to a potential diagnosis of meningococcal sepsis, leading researchers to switch cefuroxime to ceftriaxone, an antibiotic that’s more adequate for treating meningococcal infections. She also required an additional blood transfusion after a further decrease in hemoglobin and an increase in LDH levels.
After several negative tests for N. meningitidis, the diagnosis of sepsis caused by an infection with nonencapsulated N. meningitidis was confirmed following whole-genome sequencing — a method that analyzes the entire genome (the set of genes) of a given organism, including bacteria. Infections caused by this type of N. meningitidis bacteria are rare, according to the researchers.
“Complement inhibition with [Empaveli] and potential residual [Ultomiris] predisposed this patient to an unusual septic infection by nonencapsulated N. meningitidis, despite immunization,” the team wrote.
After seven days of intravenous, or into-the-vein, antibiotics, the girl’s condition stabilized, and she was discharged. She continued treatment with Empaveli for PNH and oral antibiotics in case of sudden onset of fever.
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