ORLANDO – What might Aesop have written about a race between a horse and a rabbit? Researchers from the National Institutes of Health found that the horse outran the rabbit when it came to the successful use of antithymocyte globulin as a first-line treatment for patients with severe aplastic anemia.
In a randomized trial, rabbit antithymocyte globulin (ATG) was inferior to horse ATG for the initial treatment of these patients.
"Our findings were surprising to us," Dr. Phillip Scheinberg of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Md., said in an interview at the annual meeting of the American Society of Hematology, where he presented the findings in a late-breaking abstract.
The hematologic response rate after 3 months of treatment was 62% in patients treated with horse ATG compared with 33% in those given rabbit ATG (P = .0017). Six-month hematologic response rates (the primary end point of the study) were still being evaluated at the time of the presentation, so no P value was available, but the difference in favor of horse vs. rabbit appeared to persist (69% vs. 35%).
Horse ATG is a standard treatment for patients with severe aplastic anemia (SAA) who are not candidates for stem cell transplantation, said Dr. Scheinberg. In recent studies, rabbit ATG has shown success in rescuing patients after horse ATG failures or in cases of relapse, but "there were no data showing the effectiveness of rabbit ATG as first-line therapy," he said.
Dr. Scheinberg and colleagues randomized 120 patients aged 2-78 years with treatment-naive SAA to receive either horse or rabbit ATG plus cyclosporine. Demographic and clinical characteristics were similar between the two groups.
At the time the findings were presented, 3 deaths had occurred in the horse group, compared with 14 deaths in the rabbit group. The rates of relapse and clonal evolution were similar between the groups.
The results "have immediate implications for patients and their treating physicians," Dr. Scheinberg said.
"We designed the study to show that rabbit would be superior to horse, and at the end of the study we found that it was the other way around."
Based on the study findings, horse ATG should be used as first-line therapy for all SAA patients, he said. Rabbit ATG is used in many parts of the world where horse ATG is not available, because of its presumed superiority, said Dr. Scheinberg. But the study results suggest that horse ATG should be reintroduced and made available worldwide, he said.
The results raised many questions for future research about why the rabbit ATG was not as effective as the horse ATG, Dr. Scheinberg emphasized. "Maybe the horse is doing something beneficial that we don’t appreciate. Or maybe the rabbit is doing something that is not good that we don’t understand," he said. Future studies will examine the mechanism of action of the different types of ATG, he added.
Dr. Scheinberg had no financial conflicts to disclose.