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) Gastrointestinal 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.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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