A human antibody taken intravenously can reduce or eliminate prednisone treatment for a rare blood syndrome, sparing patients the serious side effects that come with taking prednisone, according to an international study on which a University of Utah dermatology professor is senior author.
Prednisone is a corticosteroid commonly prescribed for Hypereosinophilic Syndrome, a potentially debilitating group of diseases that occurs when the body produces too many eosinophils, a white blood cell whose natural role is to defend against parasites. Untreated, the syndrome can result in damage to various human organs and systems. Prednisone can control the syndrome, but also causes a range of potentially serious side-effects, including bone loss, weight gain, skin thinning with bleeding, cataracts, hallucinations, and numerous others.
Until now, corticosteroids such as Prednisone have been the primary treatment for the syndrome, according to Gerald J. Gleich, M.D., University of Utah research professor of dermatology and the study's senior author.
In the March 20 New England Journal of Medicine, Gleich and researchers from the United States and Europe report that 84 percent of study patients who received the antibody mepolizumab significantly reduced or stopped their prednisone dosage during a 36-week trial. At the same time only 43 percent of trial patients who received a placebo were able to reduce their prednisone dosage a similar amount. Mepolizumab worked only, however, in patients who lack a particular gene. This gene, FIP1L1-PDGFRA, is present in some patients and causes an increase in eosinophils that resembles leukemia. Mepolimuzab neutralizes a factor, called interleukin 5, that causes production of eosinophils by the bone marrow.
Mepolimuzab is made by GlaxoSmithKline, and the company sponsored the study. The results of the trial have significant implications for treating the hypereosinophilic syndrome in people who can take mepolizumab, according to Gleich.
"The discovery that mepolizumab enables patients to reduce or stop prednisone shows that we have found a new treatment for the hypereosinophilic syndrome that is well-tolerated," Gleich said. "Many patients who suffer from this syndrome may be able to use this drug and avoid the side effects of steroids.
Marc E. Rothenberg, M.D., Ph.D., from the Cincinnati Children's Hospital Medical Center, University of Cincinnati, is the study's first author.
Hypereosinophilic syndrome is defined as a blood eosinophil count of more than 1,500 cells per microliter. One survey showed that from 1971-1982, a total of 50 cases of the syndrome were diagnosed at the National Institutes of Health. Survival rates vary from months to years, depending on how advanced the syndrome is at diagnosis.
The study, which was double-blind (neither the patients nor investigators knew who was taking the drug or the placebo), randomized, and placebo-controlled, took place in 26 sites in the United States, Canada, Belgium, France, Germany, Italy, and Australia. A total of 85 patients, ages 18-85, with hypereosinophilic syndrome participated. Forty-three patients received mepolizumab and 42 were given a placebo every four weeks for 36 weeks. Each group of patients also received prednisone, which was slowly reduced in dosage during the trial. The goal was to reduce the prednisone dosage to 10 milligrams or less a day for eight consecutive weeks.
At the end of 36 weeks, 95 percent of the patients receiving mepolizumab had a blood eosinophil count of less than 600 cells per microliter. Only 45 percent of patients receiving placebo had an equivalent eosinophil blood count. Half of the patients receiving mepolizumab were able to discontinue prednisone during the trial.
Mepolizumab might also benefit patients taking steroids for other diseases as well, according to Gleich.
"Steroids are also useful in many eosinophil-associated diseases, but they cause so many side effects that one goal of the therapy is to find agents that allow the doctor to reduce or stop them," Gleich said. "Mepolizumab looks like such an agent, and future studies will test if it is beneficial in common eosinophil–associated diseases such as skin and allergic problems."