In patients with paroxysmal nocturnal hemoglobinuria (PNH) who receive treatment with C5 inhibitors, suboptimal disease control has been reported, according to findings from a retrospective, observational study published in Hematology Reports.

Individuals with PNH present with hemolytic anemia, impaired bone marrow function, and thrombosis. Patients often report fatigue, excessive weakness, headaches, back pain, abdominal pain, and discomfort associated with frequent blood transfusions. Treatment, which is typically determined according to severity of disease, initially includes such supportive care as blood transfusions, anticoagulants, corticosteroids, and supplements.

When PNH progresses, complement inhibitor agents are often prescribed to block the complement cascade, as well as to prevent hemolysis and membrane attack complex formation. Treatment response among patients with PNH is evaluated by hemoglobin level, lactate dehydrogenase level, the need for transfusions, and absolute reticulocyte count.

Treatment with the C5 inhibitors eculizumab and ravulizumab targets the terminal complement protein C5 and decreases the development of intravascular hemolysis among this patient population. Use of these agents in patients with the disorder has been associated with hemoglobin stabilization and reductions in the need for transfusions. Although C5 inhibitors decrease hemolysis in many individuals with PNH, some patients continue to require transfusions and many are still anemic.

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Recognizing that the current literature lacks real-world data on hematologic parameters and clinical outcomes among patients with PNH treated with C5 inhibitors, the researchers used a real-world electronic medical record network to follow US patients with PNH for 12 months post-C5 inhibitor therapy to report on their hematologic and clinical outcomes. Patients’ hemoglobin response, transfusion need, and occurrence of breakthrough hemolysis were reported.

All data were obtained from the TriNetX Dataworks USA Network—a global federated network that includes deidentified aggregate electronic medical record data from 44 healthcare organizations that represent hospitals, and primary care and specialty providers that offer research. Patients aged 12 years or older who had been treated with an index C5 inhibitor between January 1, 2010, and June 17, 2021, and had been diagnosed with PNH prior to the index date were eligible for study inclusion.

The study participants were stratified into 3 cohorts, based on C5 inhibitor treatment history: (1) eculizumab cohort (n=143), (2) ravulizumab with prior eculizumab therapy cohort (n=43), and (3) ravulizumab eculizumab-naive cohort (n=33). The primary study outcomes were the proportions of C5 inhibitor–treated patients with PNH who experienced a hematologic response, as measured by changes in hemoglobin and lactate dehydrogenase levels from baseline.

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Results of the study showed that at 12 months following C5 inhibitor therapy, 50% to 82% of the participants remained anemic, 8% to 32% required 1 or more transfusions, and 13% to 59% experienced breakthrough hemolysis, of whom 33% to 54% had complement-amplifying conditions. Thrombosis was observed in 7% to 15% of participants, infection in 20% to 25%, and mortality in 1% to 7%.

“These findings suggest that many C5 inhibitor-treated patients with PNH experience suboptimal disease control,” the researchers concluded.


Fishman J, Kuranz S, Yeh MM, Brzozowski K, Chen H. Changes in hematologic lab measures observed in patients with paroxysmal nocturnal hemoglobinuria treated with C5 inhibitors, ravulizumab and eculizumab: real-world evidence from a US based EMR network. Hematol Rep. Published online April 21, 2023. doi:10.3390/hematolrep15020027