Relative Benefit in Survival, Reduction in TE/MAVE Risk With Eculizumab for Patients With PNH


When patients with paroxysmal nocturnal hemoglobinuria (PNH) received eculizumab, survival rates increased and thromboembolic events/major adverse vascular events (TE/MAVE) decreased.

Eculizumab benefited patients with paroxysmal nocturnal hemoglobinuria (PNH), according to a study published in European Journal of Haematology. Relative survival increased and a reduction in thromboembolic events/major adverse vascular events (TEs/MAVEs) was observed.

PNH is a rare blood disease that leads to significant morbidity and mortality, with those left untreated at a higher risk of mortality, up to 24%. The International PNH Registry is the largest global database of patients with PNH. This study aimed to “describe and compare the overall survival as well as the first incidence of TEs/MAVEs in patients with PNH while treated with eculizumab vs while untreated” using the PNH Registry database.

Patients who were enrolled in the registry from March 16, 2007, to February 14, 2022, who had complete information on their birthdate, sex, enrollment date, and treatment status were included in the study. Patients who were treated with anticomplement treatment other than eculizumab were excluded.

Platelets forming a blood clot, AI Generative | Image Credit: Катерина Євтехова -

Platelets forming a blood clot, AI Generative | Image Credit: Катерина Євтехова -

Patients were split into 2 groups: treated and untreated cohorts. Those in the treated cohort received eculizumab for at least 35 continuous days and the untreated cohort received no medication. Baseline was the date of PNH Registry enrollment for untreated patients and initiation of eculizumab treatment or PNH Registry enrollment for treated patients. HRs for the first occurrence of TEs and MAVEs were calculated.

There were 4118 patients who were included in the study. with 1613 in the treated cohort. The patients were 52.5% female and had a median (Q1-Q3) age of 38.8 (25.0-57.3) years. Patients who were treated with eculizumab were younger at the onset of the disease (median, 35.2 [24.0-53.1] vs 42.1 [25.9-59.3] years) and at baseline (median, 39.2 [28.1-56.6] vs 45.1 [29.0-61.7] years) compared with the untreated cohort.

A higher median percentage of glycosylphosphatidylinositol (GPI)-deficient granulocytes was found in patients treated with eculizumab compared with untreated patients (79.4% [54.0%-92.8%] vs 5.1% [0.5%-33.0%]). There were more patients with GPI-deficient granulocytes of 50% or more in the treated group compared with the untreated group (78.1% vs 19.6%); the treated patients also had a higher amount of patients with an lactate dehydrogenase ratio of 1.5 or more times the upper limit of normal compared with untreated patients (87.8% vs 32.4%).

A Univariable Cox proportional HR found that the mortality in patients treated with eculizumab vs those untreated was 0.51 (0.41-0.64), which indicated a 49% improvement in survival during the treated period. Patients who hadhigh disease activity (HDA) at baseline had the largest reduction in mortality risk, at 49% (HR, 0.51; 95% CI, 0.36-0.72). Significant survival benefits were found in stratified analyses in patients treated with eculizumab when clone size was 50% or more (55%; HR, 0.45; 95% CI, 0.28-0.72), patients were 40 years and older (48%; HR, 0.52; 95% CI, 0.35-0.75), and regardless of history of bone marrow failure (BMF) (history of BMF, 42%; HR, 0.58; 95% CI, 0.37-0.89; no history of BMF, 58%; HR, 0.42; 95% CI, 0.24-0.74).

The HR for TEs in untreated patients vs during treated time in treated patients was 6.26 (95% CI, 3.78-10.36). A similar result was found for MAVEs, with an HR of 6.69 (95% CI, 4.43-10.10). There was a 60% to 63% reduction in TE and MAVE risk in the treated time vs the untreated time in treated patients.

There were some limitations to this study. Control for differences in disease severity could not be fully adjusted for in treated vs untreated patients, and all-cause mortality was investigated but it is not possible to determine causes of death specific to PNH vs general causes of death. Missing data and incomplete reporting were also possible due to the nature of the study.

The researchers concluded that treatment with eculizumab was able to improve the survival of patients who used it compared with those who did not receive the monoclonal antibody untreated. Patients with HDA at baseline were able to show the most improved survival of all the patients.


Terriou L, Lee JW, Forsyth C, et al. Long-term effectiveness of eculizumab: data from the International PNH Registry. Eur J Haematol. Published online September 15, 2023. doi:10.1111/ejh.14080

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