November 2, 2009 (San Diego, California) — Patients with moderate to severe ulcerative colitis (UC) who fail or cannot tolerate infliximab (Remicade) therapy can be switched to adalimumab (Humira, Abbott Laboratories), but response to this second-line therapy might not be durable. Many of these patients undergo colectomy within 2 years, according to results of an observational retrospective study presented in a poster here at the American College of Gastroenterology (ACG) 2009 Annual Scientific Meeting.
Adalimumab has established efficacy for patients with Crohn's disease, rheumatoid arthritis, and psoriasis. Until recently, it was not known whether it was effective in UC patients; it was used off-label in this study.
The study used data from the Colitis and Crohn's Disease Center at the University of California at San Francisco, which involved 17 patients (8 men and 9 women) diagnosed with moderate to severe UC receiving adalimumab therapy. Those in the study group had previously received infliximab but went off the drug because symptoms returned (n = 12; 71%); because of adverse events (n =2;12%), because of a lack of efficacy and drug-induced lupus (n = 2), or because of a diagnosis of breast cancer (n = 1).
Although adalimumab was well tolerated, with an initial response in 13 of the 17 (76%) and complete remission in 6 (35%), symptom relief was relatively short-lived for most of the group. The median time of treatment was 7 months (range, 1 to 24 months). The study defined clinical remission as a partial Mayo score of 2 points or less with no individual score of more than 1 point; and a partial response as a decrease from baseline in partial Mayo score of more than 30% and a decrease of 2 points or more.
Within 2 years, 8 of the 13 (62%) initial responders to adalimumab deteriorated to the point where they required or their treating physician recommended colectomy.
"This is the nature of UC — [patients] stop responding to therapy because we don't have the best medications. There are no 100% cures, although some people would consider surgery a cure," Eugene Yen, MD, presenter and coinvestigator, told Medscape Gastroenterology.
Dr. Yen is now clinical director of the Center for Crohn's and Colitis at NorthShore University HealthSystem Faculty Group Practice at the University of Chicago Medical Center, in Illinois. At the time of the study, Dr. Yen was at the University of California at San Francisco.
Dr. Yen noted that among the study's limitations was that it was an observational retrospective study with a small population, although he thought it was representative. The researchers hope to follow the group in a prospective manner.
Dr. Yen said that "adalimumab is a wonderful drug for Crohn's disease, but we're just getting information on its appropriateness as the initial biologic agent for the treatment of ulcerative colitis. Meanwhile, we're still trying to find the perfect drug for severe ulcerative colitis."
Commenting on the study for Medscape Gastroenterology was Jean-Paul Achkar, MD, FACG, from the Department of Gastroenterology of the Digestive Disease Center at The Cleveland Clinic in Ohio, and chair of the educational affairs committee of the ACG. He said that he thought "it was reasonable in someone who has lost response to infliximab to try another anti-TNF [tumor necrosis factor]-alpha agent. . . . This trial points out that the ratio of benefits are short-lived," he said, adding: "What we know from Crohn's disease is that if you lose response from the first anti-TNF-alpha agent, there is a proportion of patients that will have a response to a second anti-TNF-alpha agent, but further studies are warranted before we can make any definitive conclusion."
The study received no commercial support. Dr. Yen and Dr. Achkar report have disclosed no relevant financial relationships.
American College of Gastroenterology (ACG) 2009 Annual Scientific Meeting: Abstract 307. Presented October 25, 2009.
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Cite this: Adalimumab Initially Effective in Infliximab-Resistant Ulcerative Colitis, But Effects Are Not Durable - Medscape - Nov 02, 2009.