The study found that a significantly higher proportion of patients taking the drug, cyclophosphamide, showed improvement in lung function compared with those taking a placebo. Patients taking the drug also had significant reductions in breathlessness and reported feeling more energetic and in better health.
"Until now, there has been no proven therapy for scleroderma, and 60-70% of patients die within 10 years," said Donald Tashkin, M.D., Professor of Medicine at the David Geffen School of Medicine at the University of California, Los Angeles, one of the authors of the new study on the drug.
Although previous studies have suggested that cyclophosphamide may benefit people suffering from scleroderma, this study, known as the Scleroderma Lung Study, is the first large, randomized, controlled trial to study the drug's effectiveness against scleroderma lung disease. The study, sponsored by the National Institutes of Health, was conducted at 13 centers throughout the United States.
Scleroderma is a progressive disease that leads to the hardening and tightening of the skin and connective tissues-the fibers that provide the framework and support for the body. The disease can affect the blood vessels and internal organs, and about 80% of patients also have a problem with their lungs that leads to scarring (fibrosis). This scarring is caused by inflammation, in which an abnormal number of white blood cells accumulate in the lungs. The inflammation and scarring make breathing more difficult. More than half of scleroderma deaths are due to lung-related problems, Dr. Tashkin said.
About 150,000 Americans have scleroderma. Three to four times more women than men develop scleroderma. While it can develop at any age, it most commonly begins between the ages of 25 to 55, according to the Scleroderma Foundation. The cause of scleroderma is still unknown.
Cyclophosphamide is sometimes used as a treatment for leukemia, lymphoma and other types of cancer. The study included 162 patients whose scleroderma had caused significant impairment of their lung function as well as shortness of breath. Patients had scleroderma for an average of three years before entering the study. The patients were only admitted to the study if testing showed they had active inflammation in the lung, since these patients were most likely to respond to an anti-inflammatory drug.
The patients were divided into two groups: one half received cyclophosphamide for a year and the other half received a placebo. Dr. Tashkin noted that the lung function of 5 patients receiving placebo dropped so much during the course of the study that they started receiving cyclophosphamide instead.
The study found that a significantly higher proportion of patients on cyclophosphamide showed improvement in lung function compared with those taking the placebo. Patients taking the drug also had significantly more improvement and significantly less worsening of breathlessness than those in the placebo group.
Patients taking cyclophosphamide also reported better functional ability than the placebo group; and they reported having more energy and pep while taking the drug.
The researchers reported more serious adverse events in the cyclophosphamide group compared with the placebo group, such as five cases of pneumonia in the treatment group compared with one in the placebo group. The number of deaths in each group was the same-2 patients each. "Nobody died of toxicity from the drug," Dr. Tashkin said. "We know cyclophosphamide has toxic effects, but you have to balance the efficacy of the drug against its toxicity. It's a desperate disease, and nothing else has proven effective. We feel the benefits outweigh the risks."
Next, Dr. Tashkin and his co-investigators hope to study a combination of cyclophosphamide and another drug that will fight the effects of scleroderma's lung scarring. "We found favorable effects with cyclophosphamide, but we want to do better," he said.