Biologic agents should not be used as first-line therapy for inflammatory bowel disease (IBD), according to the recommendations of a consensus development conference convened by the AGA Institute.
While certain biologic therapies have demonstrated efficacy in some patients with Crohn's disease and ulcerative colitis, especially patients with refractory or fistulizing disease, there is also evidence of serious, potentially fatal side effects, wrote Dr. Paul Rutgeerts and Dr. Steven Hanauer, co-chairs of the consensus conference, as well as the other members of the AGA Institute IBD Biologics Conference panel.
Thus, despite emerging evidence that the early use of biologics may modify the course of IBD, there is insufficient data so far to support their routine use as first-line agents, according to the group's findings, which are reported the July 2007 issue of Gastroenterology.
Biologic therapy can be considered prior to steroid use in some patients with IBD, including those for whom other therapies have failed or in whom steroids are contraindicated, the panel wrote. Additionally, use of biologic agents may be warranted in specific subgroups of patients with IBD, such as those with complex fistulas for whom conventional therapies are relatively ineffective.
The majority of available data regarding the use of biologic agents in IBD relates to anti-tumor necrosis factor (anti-TNF) drugs. In comparing the results of clinical trials of currently available anti-TNF agents approved for Crohn's disease (infliximab and adalimumab) and for ulcerative colitis (infliximab), as well as certolizumab pegol, for which approval is pending for Crohn's disease, the panel determined that the drugs, “when optimally dosed, are similarly effective in their ability to induce response and remission.”
In terms of other biologic agents, the drug etanercept, in doses that are effective in rheumatoid arthritis, “is not effective in Crohn's disease,” while the human monoclonal antibody natalizumab appears to have similar maintenance benefits to those of the anti-TNFs, “although there [are fewer] high-quality data to evaluate pertaining to induction of remission,” the authors wrote.
The degree and duration of therapeutic response to biologic agents can be affected by the development of antibodies to the drugs, which is a common occurrence, the panel stated. High-dose induction accompanied by scheduled maintenance regimens can reduce this immune response, as can immune suppression that has been initiated in advance of the biologic therapy in order to assure adequate immunomodulatory effects, they said.
The use of immune suppression with anti-TNF agents and natalizumab, however, appears to increase the risk of serious infections and neoplasia. For example, natalizumab use with concomitant immune suppression has been associated with progressive multifocal leukoencephalopathy (PML), while infliximab combined with azathioprine has been associated with neoplasia, such as hepatosplenic T-cell lymphomas. “These uncommon but serious risks require additional risk-benefit evaluations for individual patients,” the authors stated.
Despite evidence that biologics modify the course of IBD, there is insufficient data to support their routine use. DR. HANAUER