47th Annual Gastroenterology Update: Rationale for Combination Therapy in Inflammatory Bowel Disease

NOVEMBER 18, 2011
Chris Washburn, PhD
Cleveland, OH—“Over the past 10 years, our lexicon in inflammatory bowel disease (IBD) treatment has significantly changed. Instead of speaking in terms of response to therapy, we are using terms such as combination therapy, mucosal healing, and altering disease course,” said Jean-Paul Achkar, MD at the Cleveland Clinic. During his presentation, Dr. Achkar outlined the rationale for combination therapy for patients with IBD during his presentation to a packed auditorium at the Cleveland Clinic’s 47th Annual Gastroenterology Update meeting.
“We have learned several lessons with regard to anti-TNFα therapy over the past decade,” said Achkar. Although the initial response rate for anti-TNFα agents range from 64% to 58% following 2 to 6 weeks of therapy, the percentage of patients with disease remission drops to approximately 40% after 26 weeks of treatment with infliximab, adalimumab, or certolizumab pegol. When a patient no longer responds to one anti-TNFα agent, results from the WELCOME trial showed there is very little benefit to switching to a second anti-TNFα agent.
Achkar showed a graph which compared the response rates and remission rates at week 26 from the PRECiSE 2 and WELCOME trial. While certolizumab pegol may be an effective treatment option for patients failing on first-line infliximab therapy, response and remission rates are approximately 20% higher for patients who have not been exposed to an anti-TNFα agent.
As physicians aim to achieve a durable response with IBD therapy, physicians need to learn how to deal with immunogenicity as well as the loss of response to anti-TNFα treatment, said Achkar. “All 3 anti-TNFα agents are immunogenic—this is not something unique to infliximab,” he cautioned. However, results from anti-TNFα clinical trials suggest the likelihood of a patient developing an antibody to treatment with one of the biologic recombinant agents is small, he said.
Patients with shorter of IBD duration are more likely to respond to early anti-TNFα therapy, said Achkar. He showed data from subgroup analyses where patients with disease duration shorter than two years are more likely to respond to anti-TNFα treatment than those with a longer duration of disease.
In conclusion, Achker said there is room for improvement of response rates with current treatment approaches.  “There may be a limited window of time to maximize anti-TNFα therapy, as evidenced by the observed loss of response over time, the need to increase the dose of anti-TNFα therapy, and immunogenicity,” he said.

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