In individuals with paroxysmal nocturnal hemoglobinuria (PNH), treatment with eculizumab is not associated with optimal clinical outcomes, with patients continuing to experience an ongoing burden of disease, according to findings from a retrospective study published in the European Journal of Haematology.

Patients with PNH suffer hemolysis, with an elevated risk for thrombosis, along with a potential sudden onset of hemoglobinuria, anemia, bone marrow failure, and fatigue. The monoclonal antibody eculizumab targets complement C5, thus inhibiting terminal complement activation. Although the agent has demonstrated disease improvements among some individuals with PNH, unmet needs continue to exist in other eculizumab-treated patients.

The researchers sought to characterize the real-world clinical profile of patients treated with eculizumab by describing their short- and long-term clinical and laboratory outcomes. The study used medical records of eculizumab-treated patients with PNH from the University Hospital Essen, in Essen, Germany. They evaluated breakthrough hemolysis, transfusion dependence, and hematologic response among the participants.

In the current study, breakthrough hemolysis was defined as “one or more new symptoms or signs of intravascular hemolysis, including fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia (hemoglobin <10 g/dL), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction in the presence of elevated LDH [lactate dehydrogenase] (≥2x the upper limit of normal [ULN] after reduction of LDH to ≤1.5xULN).”

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Hematologic response to treatment was classified as being complete, major, good, partial, minor, or no response. Those with a complete response required no transfusions, had a stable hemoglobin level, and had no evidence of hemolysis. A major response was reported in those who required no transfusions, had normal hemoglobin levels, but had evidence of hemolysis. Those with a good response required no transfusions, but exhibited chronic mild anemia and evidence of hemolysis. A partial response was described as having moderate anemia and/or requiring occasional transfusions. In those with a minor response, regular transfusions were needed (3-6 within 24 weeks); in participants with no response, regular, frequent transfusions were required (>6 within 24 weeks).

Eighty-five individuals were diagnosed with PNH, with 76 of them receiving eculizumab therapy for 24 weeks or more and included in the study. Mean follow-up after initiation of eculizumab was 5.59±3.28 years. Overall, 50% of the study cohort comprised women. The median participant age was 37.5 years. Median time from PNH diagnosis to initiation of eculizumab was 558 days; 74% of participants began taking eculizumab within 5 years of diagnosis.

In all, 57 participants had detailed data on hematologic response available in the initial 24 weeks. Of them, 7% reported a complete response and 9% had a major response; there were good and partial responses experienced by 21% and 30% of participants, respectively; 16% exhibited a minor response and 18% had no response.

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Further, 38% (29 of 76) of patients received a blood transfusion. Among those with available data, 37% (22 of 59) of participants had an LDH greater than 1.5x ULN. Overall, 13% of the 76 patients experienced breakthrough symptoms and 8% had breakthrough hemolysis.

“Future exploration of other new therapies that improve patient outcomes could help to address unmet medical needs [in PNH],” the authors concluded.


Versmold K, Alashkar F, Raiser C, et al. Long-term outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in a real-world setting. Eur J Haematol. Published online March 27, 2023. doi:10.1111/ejh.13970