There are three phenotypes, or categories of disease presentation in Crohn's disease: stricturing disease (which causes narrowing of the bowel), penetrating disease (which causes fistulae or abnormal connections of the bowel), and inflammatory disease (which causes primarily inflammation).
Fistulizing disease
Infliximab was first used for closure of fistulae in Crohn's disease in 1999. In a 94-patient phase II clinical trial, the researchers showed that Infliximab was effective in closing fistulae between the skin and bowel in 56-68% of patients. A large 296-patient Phase III clinical trial called the ACCENT 2 trial, showed that infliximab was additionally beneficial in maintaining closure of fistulae, with almost two-thirds of all patients treated with the 3 initial doses infliximab (Remicade) having a fistula response after 14 weeks, and 36% of patients maintaining closure of fistulae after a year, compared with 19% who received placebo therapy. This final trial resulted in the FDA approval of the drug to treat fistulizing disease.
Inflammatory disease
Infliximab has also been used in order to induce and maintain remission in inflammatory Crohn's disease. The ACCENT 1 trial was a large multicentre trial that showed that 39 to 45% of patients treated with infliximab who had an initial response to it, maintained remission after 30 weeks, compared with 21% who received placebo treatment. It also showed a mean maintenance of remission from 38 to 54 weeks compared with 21 weeks for patients who received placebo treatment.
Crohn's patients have flares of their disease between periods of disease quiescence. Severe flares are usually treated with steroid medications to obtain remission, but steroids have many undesirable side effects, and therefore some gastroenterologists are now advocating for the use of infliximab as the first drug to try to get patients into remission. This has been called the ''top-down'' approach to treatment.
Further Reading
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