New Study Confirms that Horse ATG is Significantly More Effective than Rabbit ATG for Treating Severe Aplastic Anemia

Original Publication Date: 

A study published in the August 4, 2011 New England Journal of Medicine compared the effectiveness of horse vs. rabbit antithymocyte globulin (ATG) for the treatment of severe aplastic anemia. Conducted by researchers at the National Institutes of Health (NIH), this study examined the results of 120 severe aplastic anemia patients ranging in age from 2 to 77 who received either the horse ATG (Atgam®) or rabbit ATG (Thymoglobulin®). Investigators found that horse ATG significantly outperformed rabbit ATG as a first line therapy for aplastic anemia.

The most important findings from this study are:

  • Six months after starting treatment, 68 percent of patients given horse ATG had improved blood counts, compared to only 37 percent of patients who received rabbit ATG.

  • Three years after treatment 96 percent of patients given horse ATG were still alive, compared with 76 percent of those who received rabbit ATG as first line therapy.

The Aplastic Anemia & MDS International Foundation understands that patients and their family members will have questions about how this new information may affect or alter their treatment for aplastic anemia. To help you understand this study and its implications for you or your loved one, we interviewed the study’s primary investigator, Phillip Scheinberg, MD, a clinician and researcher at the Hematology Branch, National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health. He discussed the study and its findings, as well as the potential effect on treatment options for those with aplastic anemia.


This transcript below was taken from an interview conducted with Phillip Scheinberg, MD, on August 9, 2011.


Can you please describe the study, including the background and methods?

This study compared the efficacy of two forms of ATG, horse and rabbit, as first line therapy in severe aplastic anemia (SAA). These are the only two licensed forms of ATG in the U.S. These treatments are produced in animals and contain several antibodies that kill human T lymphocytes, which are the cells implicated in destroying the bone marrow cells in humans with SAA. Both ATG types help suppress the immune system, and by doing this help the bone marrow heal itself and produce more blood cells. The horse therapy is the only currently FDA-approved aplastic anemia treatment in the United States. The treatment with horse ATG is good, but not ideal, so at the NIH, we have sought better therapies for patients with this disease.

Rabbit ATG is a newer form of ATG and is stronger in the sense that it suppresses more of the immune system and has been shown to work in some patients with aplastic anemia but has not been extensively studied as first line therapy. We have hypothesized that rabbit ATG would be better (or at least as good) as therapy for aplastic anemia, and this was the commonly held notion at the time when we conceptualized this study in 2005.

Patients enrolled in this trial through a process called randomization – a process where patients are assigned to receive one of the drugs by chance, not by choice. The ATG they were selected to receive was given only once and then they were followed for six months to see if they responded to the treatment. The objective of the study was to examine the response rate at six months. When the study was first developed, we hypothesized that rabbit ATG would be the better agent.

How did you define severe aplastic anemia for this study?

SAA was defined by conventional criteria, by having two of the following three counts: a neutrophil count (a type of white blood cell) of less than 500, a reticulocyte (very young red blood cells) count of less than 60,000, or a platelet count of less than 20,000.

Does this study only affect patients with severe aplastic anemia?

Yes, this study was conducted only in patients who had SAA. Aplastic anemia can be severe or moderate, but patients with moderate aplastic anemia were not included in this study. This study was for those who had lower blood counts and were receiving frequent transfusions of blood and/or platelets.

What are the most important findings from this study?

The major finding was that patients who received rabbit ATG did not do as well as the patients who received horse ATG as their first line therapy – and by ‘not doing as well’ I mean that we unexpectedly saw fewer responses in patients who received rabbit ATG as compared to those who received horse ATG. This was an unanticipated result. The belief in the hematology community was that rabbit ATG was at least as effective, if not better, than horse ATG and our results at the end of the study showed quite the opposite.

Why are these findings important for patients?

These findings are important because in the United States, both horse and rabbit ATG are available. So we have seen U.S. patients receiving either horse or rabbit ATG as first round of immunosuppressant therapy. We hope that based on the results of this study that this will no longer be the practice, and patients will preferentially receive horse ATG as their first line therapy.

In other parts of the world this is a little more problematic as horse ATG is not available in European, Asian, or Latin American markets. It was removed a few years ago, and the implications for patients in these parts of the world are more immediate in the sense that they presently do not have access to the better ATG, based on the results of our study.

What were the exact findings that were so surprising to you?

The main objective of the study was to see the response after six months of receiving therapy --response meaning the blood counts get better – hemoglobin goes up, platelet count increases, neutrophil counts go higher, all to the point where patients aren’t at significant risk of having complications associated with low blood counts, and no longer require transfusions. Using that parameter, patients who received horse ATG were able to achieve those parameters more frequently compared to patients who received rabbit ATG as first line therapy.

The important point here is to note that some patients who received rabbit ATG did respond well and continue to do well, but the frequency of patients who received an optimal response from horse ATG was higher compared to those who had the rabbit ATG.

It is important to note that in aplastic anemia, response to therapy is a critical parameter because not only does it contribute to better blood counts, but it also is associated with better overall long-term survival rates. Because of this, we saw better survival rates of patients who had horse ATG therapy.

For a newly diagnosed aplastic anemia patient, what does this mean?

This means that if patients are going to receive some form of immunosuppressive therapy for SAA, based on the results of our study, they should be receiving the horse ATG as their first line treatment.

For an aplastic anemia patient who has already been treated with either rabbit or horse ATG, what does this mean?

The very important parameter of response at six months needs to be assessed. If they do not respond to rabbit ATG, then our study suggests that receiving horse ATG is reasonable. At NIH, we have a protocol where we do offer patients horse ATG to those who did not respond to an initial round of rabbit ATG. This protocol is still accepting patients right now. Find out more about this protocol at now at

If a patient is actively being treated with ATG now, what does he or she need to know?

I would not change anything in mid-course. If someone finished rabbit ATG recently, they should wait and see how they respond. Responses can be achieved with rabbit ATG and they can be robust responses. We really need up to 6 months to tell how a patient is doing with [either] ATG therapy. There can be an indication of response as early as three months, but we usually need 6 months to be sure. If we see no evidence of improved blood counts after 6 months we start to look for other options for the patient. The percentage of patients who start to show improvement after six months is low.

Do the study findings apply differently to pediatric patients than to adult patients?

For this study, we reported on the efficacy of horse and rabbit ATG as first line therapy for patients of all ages. We did not break out the results for pediatric and non-pediatric patients. Looking at different age groups may be done in the future.

What would you tell the parents of a child considering treatment with ATG right now?

With children who have SAA, if there is a matched sibling donor, a transplant would be the preferred initial form of therapy. In the absence of a matched sibling donor, immunosuppressive therapy is the standard option. Based on what we have learned, horse ATG should be the first treatment that is used. An earlier study of ours indicated that children do particularly well with horse ATG, when compared to patients of other ages.

What do the study results mean for aplastic anemia patients living outside the United States where horse ATG is not licensed or approved to treat aplastic anemia?

The problem in these areas is more immediate for patients who don’t have access to this drug. Our European counterparts and those in other areas of the world are taking this new data very seriously. They are working with the regulatory agencies in their countries to see if they can bring back horse ATG as quickly as possible so that patients who are undergoing their first therapy can have horse ATG, which we believe to be better as first line treatment.

Is there a next step or logical follow-up for this study?

We are surprised by these results and are working hard in the laboratory to try and understand the factors that have led to such a big difference and in a direction that was opposite of what was anticipated. We want to know what the differences are between the two types of ATG that are responsible for this. We are starting to get some clues but it’s still preliminary data, which we hope to report at the 2011 American Society of Hematology meeting in December. We think this understanding is critical, as it will help us to know what made the horse ATG work better than rabbit ATG. If we can understand this, it will help us focus on the positive aspects of horse ATG and avoid the negative aspects of rabbit ATG when developing new therapies for aplastic anemia.

Is there any final advice you would have for an aplastic anemia patient who may be considering ATG treatment?

Aplastic anemia is a truly rare disease, and there might not be a lot of experience in treating it in some smaller communities. We recommend that patients be seen and evaluated at a larger, university- based tertiary medical center where more patients with the same disease are seen. This is not only to help with the management of the disease, but also with the administration of some of the drugs (like ATG) which can have significant side effects. So it’s better for patients to be seen by experienced doctors and staff who have experience in this area and with these treatments.

Additional information on this study can be found in this official NIH Press Release.

View an abstract of this article on the National Library of Medicine’s PubMed portal.