Rare Blood Vessel Disease Could Have New Treatment Option
Posted Jul 14 2010 10:00am
Rituximab could be first new therapy in 40 years against specific forms of vasculitis, researchers say.
By Amanda Gardner HealthDay Reporter
WEDNESDAY, July 14 (HealthDay News) -- A drug already used to treat lymphoma and rheumatoid arthritis shows promise as an option to treat rare forms of vasculitis, a disease affecting the blood vessels, according to two new studies.
The drug, rituximab, appeared to be as effective as the current standard, cyclophosphamide, in treating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
Rituximab may even be superior to cyclophosphamide in treating disease recurrences, the researchers found.
This is the first time in 40 years that a new drug has emerged to treat these conditions, according to the authors of the studies, both appearing in the July 15 issue of the New England Journal of Medicine.
"This trial has demonstrated for the first time there is an effective alternative to cyclophosphamide for remission induction, and there are a variety of results that make us think that rituximab should be the treatment of choice for remission induction," said Dr. John H. Stone, director of clinical rheumatology at Massachusetts General Hospital in Boston, referring to one of the studies, of which he was first author.
"I think these are two very important pivotal studies that bring hope to patients with ANCA vasculitis. And despite the fact that they are relatively small studies, they are proof of principle that this medicine has the ability to get rid of the group of cells that produce the [antibody]," added Dr. Ronald J. Falk, director of the University of North Carolina Kidney Center at Chapel Hill, and author of an accompanying editorial. "These antibodies are actually causing the disease, so by getting rid of them, one is really now attacking the disease cause rather than just disease symptoms."
"ANCA-associated vasculitis consists of two primary diseases, Wegener's granulomatosis and microscopic polyangitis," explained Stone.
The conditions are characterized by the presence of specific antibodies, which are made by plasma cells derived from B cells. These antibodies attack immune cells, leading to inflammation of the blood vessels that eventually affects the organs.
Rituximab targets B cells.
"Until the late 60s, early 70s, these were fatal diseases. We had no effective treatments at all," Stone said.
But at that time, the drug cyclophosphamide was shown to get the diseases under control, albeit at considerable cost, namely an increased risk of cancer, damage to the bladder, infections and infertility.
Since then, no other drug has emerged as a contender to cyclophosphamide, and so no head-to-head comparisons have been conducted.
"It was considered unethical up until now to perform such a trial," said Stone.
Stone and his team randomly assigned 197 patients with severe Wegener's granulomatosis or severe microscopic polyangitis to receive either rituximab or cyclophosphamide. Both groups were also taking glucocorticoids.
After six months, 64 percent of those in the rituximab arm and 53 percent in the cyclophosphamide were in remission and no longer needed steroids.
In patients who had relapsed, 67 percent of those receiving rituximab were in remission versus only 42 percent in the control group.
The trial was partially funded by Genentech, which makes rituximab.
The second research team, led by Dr. Rachel Jones of Addenbrooke's Hospital, Cambridge, U.K., randomly assigned 44 patients with newly diagnosed ANCA-associated vasculitis and kidney problems to rituximab or cyclophosphamide. Patients in both groups also took glucocorticoids.
Remission rates were similar in both arms: 76 percent of those taking rituximab and 82 percent of those taking cyclophosphamide.
But there was also a high rate of side effects in both groups (42 percent for rituximab and 36 percent for cyclophosphamide). Eighteen percent of patients in each group died.
Those results are sobering, Falk said. "Both studies had greater side effects than previously anticipated with rituximab. We would have hoped for far less deaths, so we need to proceed with caution," he said.
Both sets of study authors pointed out that larger and longer trials are needed to see how the drugs compare over the long haul.
(SOURCES: John H. Stone, M.D., director, clinical rheumatology, Massachusetts General Hospital, Boston; Ronald J. Falk, M.D., director, University of North Carolina Kidney Center, Chapel Hill; July 15, 2010 New England Journal of Medicine)