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Study shows drug can heal, reduce recurrence
of fistulas in Crohn's disease
BOSTON - February 25, 2004 - An international study has found
that maintenance therapy with the drug infliximab, a monoclonal
antibody used to treat Crohn's disease, can prevent or delay the
recurrence of fistulas, a common complication of that inflammatory
bowel disorder. As reported in the February 26 New England Journal
of Medicine, patients receiving infliximab on a regular basis
were twice as likely to avoid fistula recurrence than were patients
receiving a placebo.
The study was largely supported by the pharmaceutical firm Centocor,
a subsidiary of Johnson & Johnson, which markets infliximab
under the brand name Remicade.
Crohn's disease is a chronic inflammatory disorder of the digestive
tract that affects about half a million people in the U.S. Patients
with more severe symptoms may develop fistulas - openings from affected
areas of the intestine into other organs or onto the skin, often
around the anus. The presence of fistulas can seriously impact patients'
quality of life and increases the likelihood of surgical treatment,
which may not have satisfactory results. Infliximab, which targets
the inflammatory protein tumor necrosis factor, has been shown in
previous research to reduce symptoms in patients without this complication
and to heal fistulas over a limited period of time.
"Fistulas can be a devastating complication of Crohn's disease,"
says Bruce Sands, MD, of the Massachusetts General Hospital (MGH)
Gastroenterology
Unit, lead author of the report. "While neither medical
nor surgical therapy is perfect in treating this complication, our
study has shown that maintenance treatment with infliximab can produce
durable closure of fistulas in many patients."
The current study - carried out at 45 sites in North America, Europe
and Israel - enrolled adult patients with fistulizing Crohn's disease
not previously treated with infliximab. Almost 300 participants
completed a preliminary phase of treatment, receiving three intravenous
doses of infliximab over six weeks. They were evaluated several
weeks later to determine whether they responded to the infliximab
treatment - defined as a 50 percent or greater reduction in the
number of draining fistulas - and subsequently randomized into groups
receiving either continuing infliximab doses every eight weeks or
placebo infusions. Neither participants nor the researchers knew
to which groups patients were assigned.
Among participants who initially showed a response to infliximab,
fistulas recurred much less frequently among those receiving continuing
treatment than in the placebo group. At the end of the 54-week study,
almost half those receiving infliximab still showed some response,
with more than one-third remaining free of fistulas. Less than 20
percent of the placebo group stayed fistula-free during the same
time period.
"The benefits of infliximab in this patient population go beyond
closing of fistulas," Sands explains. "These patients
also have a reduction in other symptoms and demonstrable improvement
in their quality of life. While infliximab is not effective for
all patients, the impact can be remarkable for those who do respond."
Sands is an assistant professor of Medicine at Harvard Medical School.
The researchers also note that continuing treatment at fixed intervals
appears superior to waiting until symptoms recur to reinstate therapy.
Patients in the placebo group who redeveloped fistulas during the
study could resume infliximab treatment, but although many experienced
a renewed response to the medication, they all had to deal with
worsening symptoms. Since infliximab does suppress part of the immune
response, patients on sustained therapy should be followed closely
for evidence of infection or other serious side effects.
Additional authors of the NEJM paper include senior author Sander
van Deventer, MD, PhD, of Academisch Medisch Centrum, Amsterdam;
Frank Anderson, MD, Vancouver Hospital; Charles Bernstein, MD, University
of Manitoba; William Chey, MD, D.Sc., Rochester Institute for Digestive
Diseases and Sciences; Brain Feagan, MD, University of Western Ontario;
Richard Fedorak, MD, University of Alberta; Michael Kamm, MD, St.
Mark's Hospital, London; Joshua Korzenik, MD, Washington University
School of Medicine; Bret Lashner, MD, Cleveland Clinic Foundation;
Jane Onken, MD, Duke University; Daniel Rachmilewitz, MD, Tel Aviv
Sourasky Medical Center; Paul Rutgeerts, MD, PhD, University Hospital
Leuven, Belgium; Gary Wild, MD, PhD, Montreal General Hospital;
and Douglas Wolf, MD, Atlanta Gastroenteroloy Associates. Co-authors
from Centocor are Paul Masters, Susan Travers, MD, and Marion Blank,
PhD.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $350 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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