Embargoed for Release: April 1, 2003, 4:00 PM EST
Embargoed for Release: April 1, 2003, 4:00 PM EST
Sickle cell anemia patients who took the drug hydroxyurea over a 9-year period experienced a 40 percent reduction in deaths, according to the first study to evaluate whether the treatment prolongs life, announced the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.
The study of 299 adult sickle cell patients with moderate to severe forms of the disease, found that improved survival was related to the benefits associated with hydroxyurea treatment - an increase in fetal hemoglobin and reduced episodes of severe pain "crises" and chest syndrome, a pneumonia-like illness. The results were published in the April 2 issue of The Journal of the American Medical Association.
Previous research has shown the benefits of hydroxyurea in reducing the symptoms of the most severely affected sickle cell patients - those who have 3 or more painful crises each year.
"The current study shows that hydroxyurea can improve the survival of the sickest patients. Now there is new hope for these patients, who typically die 10 to 15 years earlier than patients with milder cases," said NHLBI Director Claude Lenfant, M.D.
Patients in the new study were originally participants in the NHLBI's Multicenter Study of Hydroxyurea (MSH) in Sickle Cell Anemia. That clinical trial was designed to test whether hydroxyurea reduced symptoms of the disease compared to placebo in patients who had 3 or more crises per year. Patients were randomly assigned to hydroxyurea or placebo and the study was "double-blinded" indicating neither patients nor physicians knew who was taking the drug.
Over 2½ years, the drug resulted in an almost 50 percent reduction in the number of painful crises and episodes of chest syndrome. Patients on hydroxyurea also required about 50 percent fewer transfusions and hospitalizations. These results, reported in 1995, were reviewed by the Food and Drug Administration (FDA) and hydroxyurea became the first FDA-approved drug for the treatment of sickle cell anemia.
In the new long-term "observational" study, patients selected with their physicians whether to continue, start, or stop treatment with hydroxyurea. Seventy-five (25 percent) of the original 299 patients died during the 9-year study. According to study authors, this statistic reflects the severity of the disease as required by the study design, and the high death rate in adults with sickle cell anemia.
Among study participants, the death rate was 28 percent for those with the lowest fetal hemoglobin level compared to a 15 percent death rate for those with the highest level of fetal hemoglobin. Fetal hemoglobin inside red blood cells of sickle cell anemia patients may prevent these cells from becoming sickled and rigid, hallmarks of the inherited disease. Hydroxyurea is believed to stimulate the production of fetal hemoglobin.
The new study also found that patients with 3 or more painful episodes per year during the trial had a 27 percent death rate versus a 17 percent death rate for those with less frequent episodes.
"Hydroxyurea's ability to reduce complications in the sickest patients is strongly connected to lower death rates," said Duane Bonds, M.D., study co-author and project officer for the MSH Patients' Follow-up Study. "These results also confirm that the benefits of hydroxyurea persist. After the original trial ended, we didn't know if the benefits of the drug would be long term," added Bonds.
The new study also has important implications for significantly decreasing health care costs, said Bonds. Patients with more severe forms of the disease are seen in the emergency room and are hospitalized more frequently than patients who are less severely affected.
According to lead investigator Dr. Martin Steinberg, who is Director of the Center of Excellence in Sickle Cell Disease at Boston University School of Medicine, the latest research has important implications for the treatment of sickle cell anemia. "Presently only a minority of eligible patients are taking hydroxyurea. Our study strongly suggests that adults with sickle cell anemia and clinically significant complications of their disease, like frequent painful episodes and the common pneumonia-like events, should take hydroxyurea under the supervision of a knowledgeable physician," Steinberg said.
"Most people who take this medication will feel better; we now know they will live longer," Steinberg added.
Patients in the study will be followed for an additional 5 years, noted Bonds, who also added that hydroxyurea studies in children are planned.
Sickle cell anemia is an inherited disease that is most common among people whose ancestors come from Africa, the Middle East, the Mediterranean basin, and India. In the U.S., it affects primarily African Americans, about 72,000 of whom have the disease. One in 12 African Americans carries the sickle cell trait.
In patients with the disease, molecules of sickle hemoglobin stick to one another, forming long rods inside red blood cells and causing these cells to take on a sickle shape and become rigid. The sickled red cells are unable to squeeze through tiny blood vessels, depriving tissue of an adequate blood supply and causing painful episodes.
To interview Dr. Bonds, contact the NHLBI Communications Office at 301- 496-4236; to interview Dr. Steinberg, call Gina DiGravio at Boston Medical Center at 617-638-8491.