Eculizumab reduces hemolysis, thrombosis in paroxysmal nocturnal hemoglobinuria

Eculizumab reduced the presence of hemolysis, thrombosis and the need for red blood cell transfusions in patients with paroxysmal nocturnal hemoglobinuria, according to data presented at the Congress of the European Hematology Association in Madrid.

These findings persisted regardless of high disease activity.

“Ten years after the approval of eculizumab (Soliris, Alexion Pharmaceuticals), we continue to learn about its effectiveness in paroxysmal nocturnal hemoglobinuria (PNH) and it is reassuring that these registry data are consistent with clinical study results,” Peter Hillmen, MB ChB, PhD, professor of experimental hematology at St. James University Hospital in Leeds, United Kingdom, said in a press release. “These real-world data suggest that even patients who do not have high disease activity or progression from aplastic anemia to hemolytic PNH can benefit from eculizumab. Further, the registry data continue to support that early diagnosis and treatment improve health outcomes for patients with PNH.”

PNH is an extremely rare autoimmune blood disorder that affects between one and 1.5 persons per million. Median age of diagnosis is between 35 and 40 years, and approximately 10% of all patients first develop symptoms at age 21 years or younger. Before the introduction of complement inhibitors, about one-third of patients with PNH did not survive more than 5 years from the time of diagnosis.

Eculizumab — approved by the FDA and the European Union in 2007, and by Japan in 2010 — is a monoclonal antibody targeting C52 and is the first and only treatment for patients with PNH to reduce the destruction of red blood cells.

Researchers stratified 3,011 patients from the International PNH Registry into treatment status — ever treated or never treated with eculizumab — and the presence or absence of high disease activity at baseline. Researchers defined high disease activity as lactate dehydrogenase ratio at least 1.5 times the upper limit of normal — used as evidence of hemolysis — and history of fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia, major adverse vascular event, dysphagia or erectile dysfunction.

Median durations of follow-up ranged from 1.5 years to 3.1 years.

Patients with high disease activity experienced more pronounced activity with eculizumab, but patients without high disease activity also benefitted.

Researchers noted eculizumab-treated patients had a higher disease burden at baseline. For instance, a greater proportion of patients treated with eculizumab had a history of major adverse vascular events in the high disease activity cohort (33.3% vs. 13.7%) and non-high disease activity cohort (33% vs. 10%).

However, after treatment, these differences narrowed in the high disease activity cohort (3.9% vs. 3.3%) and non-high disease activity cohort (5.3% vs. 2.1%).

Thromboembolism rates per 100 person years were 3.9 before baseline and 0.7 after baseline in the treated population, and 0.8 before baseline and 1 after baseline for those never treated.

Mean changes in lactate dehydrogenase ratios between baseline and last follow-up were –5.3 for patients treated with eculizumab compared with –0.5 for those never treated among those with high disease activity, and –2.3 for those treated and 0.2 for those never treated in the non-high disease activity cohort.

In the high disease activity cohort, treatment with eculizumab led to higher rates of red blood cell transfusion independence (37.6% vs. 15.8%) and a greater mean score improvement on the FACIT-Fatigue scale (4.1 vs. 0.5).

The most frequently reported adverse events with eculizumab included headache, nasopharyngitis, back pain and nausea.

“Our analysis of real-world data from the International PNH Registry has demonstrated that treatment with eculizumab was associated with improved outcomes in patients with high disease activity,” Hillmen and colleagues wrote. “Our findings are consistent with the notion that patients with high disease activity, including those with a history of major adverse vascular events, should be treated with eculizumab.” – by Chuck Gormley

Reference:

Hochsmann B, et al. Abstract S498. Presented at: Congress of the European Hematology Association; June 22-25, 2017; Madrid.