|
ROCHESTER, NY -- September 16, 2004 -- Rituximab, a drug now used
to treat a type of cancer, appears to be very effective at treating
lupus, with just one injection easing symptoms in several patients
for a year or more. The results of the clinical trial involving
17 patients are in the August issue of Arthritis and Rheumatism.
The finding has its roots in a hypothesis put forth by the team
of physicians at the University of Rochester Medical Center who
did the study. They suspected that because lupus involves the same
immune cells as lymphoma, a drug successful at treating lymphoma
might also help lupus patients. So doctors tested the medication
rituximab, approved in 1997 to treat lymphoma, in patients with
the chronic inflammatory disease where the immune system mistakenly
attacks a person's own tissues.
The results bear out the hypothesis. Eleven of the 17 patients
had a significant drop in immune cells known as B cells, and the
health of those patients improved significantly, an improvement
that was evident for the 12 months that the study lasted. Several
were able to reduce or go off their traditional lupus medications.
"In most patients, their lupus improved significantly,"
says rheumatologist R. John Looney, M.D., who led the study. "Since
lupus differs a great deal from person to person, the ways that
patients improved varied. Some had less joint pain; some had fewer
skin rashes. But everyone who had fewer B cells had significantly
improved health.
"These patients were treated for a very brief period of time,
and some of them are still doing just great, several years later."
The benefit wasn't as marked for everyone, including patients who
did not receive the full dose of the medicine in the "dose-escalation"
study, as well as African-American patients. Scientists are investigating
the differences.
Unlike many autoimmune diseases that target a specific system or
organ, lupus can affect a person's joints, skin, blood, kidneys,
and even organs like the lungs and brain. Fatigue, arthritic joints,
and infections are among the most common symptoms. Many patients
live a normal life while taking medicine and working with a doctor
to keep tabs on the disease, perhaps feeling some joint pain or
having a rash occasionally, while others are debilitated by the
illness and have severe infections or organ failure. Women are about
10 times as likely as men to be diagnosed with lupus. Doctors estimate
that anywhere from about half a million to 1.5 million people in
the United States have the disease.
"Some patients don't need much treatment, while others need
all you can offer and more," says rheumatologist Ignacio Sanz,
M.D., an author of the paper and a lupus expert.
Besides the drug's success in treating the disease, scientists
noted the lack of significant side effects with rituximab. Some
patients had a reaction to the infusion of the medicine, but in
the study, it occurred far less often than it does with cancer patients
taking the drug.
Current lupus treatments, in contrast, are laden with severe side
effects. The anti-inflammatory drugs used to dampen the immune system
leave patients vulnerable to infection, while steroids at high levels
can cause an array of problems, everything from thinning bones,
weight gain, weak muscles, and heart disease to glaucoma and depression.
The difference in side effects is a result of the precision, or
lack thereof, of the medicines. Current lupus treatments affect
nearly all the cells of the body, including healthy and vital cells.
In contrast, rituximab targets only B cells and is aimed at lowering
their numbers. That's why the drug is available to lymphoma patients:
Most have too many B cells, which make antibodies that flag down
and kill microbes and other invaders in the body.
Lupus is also a problem with B cells: They're found in the wrong
proportion in the body's blood and tissue, and they're often misguided,
making too many antibodies that mistakenly attack the body itself.
The infighting clogs up the body with cellular debris, causing a
variety of symptoms; then when the immune system detects the problem,
it tries to ease up, leaving the patient open to infection.
"Lupus patients tend to have fewer B cells than normal, but
their B cells are hyperactive and function in a very abnormal way,"
says Sanz. "The immune system is hyperactive but disorganized;
it's over-reacting to some things but not enough to other things."
It was Looney's idea to target B cells to treat lupus. A great
deal lot of traditional research had pointed to other immune cells
known as T cells as the major culprit. But Looney and his team uncovered
a more complicated process than had been imagined, where cooperation
between B and T cells is at the core of the disease. The success
with rituximab opens up a whole new vista - targeting B cells, reducing
their numbers, and ridding the body of errant B cells - for treating
the disease.
The Rochester team is now helping to design a much larger study
of patients that may begin within the next year or so at multiple
sites around the country, including Rochester.
"Our basic knowledge of lupus has been increasing exponentially
during the past few years, but there have been few new treatments,"
says Sanz, who heads the University's NIH-funded Autoimmunity Center
of Excellence, where lupus is one of three diseases studied by two
dozen researchers. "Prognosis has improved because of better
support therapies like blood pressure control, anti-cholesterol
drugs, dialysis and antibiotics, but this is the first really new
and targeted therapy to come along in a long time."
The medication for the study was supplied by Genentech, Biogen Idec,
and Roche, which make and market Rituxan, the brand name for rituximab.
The study was also funded in part by the National Institute of Arthritis
and Musculoskeletal and Skin Diseases and the Lupus Foundation of
America.
In addition to Looney, Sanz, and Anolik, other authors of the paper
are nurse Debbie Campbell; Raymond Felgar, M.D., Ph.D.; Faith Young,
M.D.; Lois Arend, M.D., Ph.D., and James Sloand, M.D., all of the
University of Rochester; and Joseph Rosenblatt, M.D., of the University
of Miami, formerly of Rochester.
|
Message
Boards
