A smaller cohort published by Baert showed that in patients receiving 5 mg/kg infliximab for induction, 61% developed antibodies. with 26% of placebo patients reached the primary end point of a 50% reduction in draining fistulas from baseline. Fistula closure was seen in 46% of all infliximab patients compared with 13% of placebo-treated patients. Time to response was a mean of 2 weeks with mean response duration of 86 days . This was the first clear evidence that infliximab was efficacious in the treatment of fistulizing CD. With advances in imaging, the true definition of fistulae healing has come into question. Recent studies using endoscopic ultrasound and magnetic resonance have documented active inflammation prior to treatment with anti-TNFs; 46% of these patients had cessation of drainage, a common end point in trials, but only 28% showed complete healing on magnetic resonance imaging . In the future, studies will need to address the small sample size and investigators will need to determine how to best assess for fistulae healing C clinically or radiographically . A smaller cohort study of 26 patients with perianal fistulizing disease showed 50% complete remission after infliximab treatment. Factors associated with remission included the absence of active intestinal disease and active proctitis . A subsequent study of 99 patients with perianal CD also showed promise: 42.5% with ulcers, 18.2% with strictures and 32.3% with fistula had a complete response (closure of all fistulae) with infliximab . For longer term outcomes, the ACCENT II study followed fistulizing patients who had an initial response to infliximab at 14 weeks. In this randomized placebo-controlled trial, 36% of patients in the infliximab group (5 mg/kg every 8 weeks) compared with 19% in the placebo group had the absence of draining fistula at the end of the study . More recently, a small study assessed the role of infliximab in postoperative recurrence in CD patients undergoing an ileocolic resection (n = 24) who received either inflixmab or placebo induction followed by an every 8-week infusion. There was endoscopic recurrence in 9.1% of infliximab patients compared with 84.6% in the placebo group. Clinically, 0% in the infliximab group versus 38.5% in the placebo group had a recurrence as measured by CDAI . While the numbers of patients in this study were small, these findings provided evidence that anti-TNF- mAb therapy has a place in post-operative management for CD alongside immunomodulator treatments. Adalimumab Adalimumab (Humira?, Abbott Labs [IL, USA]) is a fully human anti-TNF mAb (Tables 1 & 2). This drug is given subcutaneously, thus avoiding the need for infusions that are required with infliximab administration. In addition, it is a fully human antibody, which has been proposed to decrease its immunogenicity, avoiding the production of anti-mAbs that have been reported Ruboxistaurin (LY333531) with infliximab. Itgam However, it has become clear that any of these agents, including adalimumab, can induce antibody formation that can be associated with local or systemic reactions. The CLASSIC-I trial, a 4-week, double-blind, placebo-controlled, randomized trial, demonstrated that adalimumab can be used for the induction of remission in patients with moderate-to-severe CD. In patients receiving doses of 80 mg of adalimumab Ruboxistaurin (LY333531) or greater at week 0 and 40 mg of adalimumab or greater at week 2, there was a statistically significant difference in patients achieving remission compared with placebo (24% with 80 mg/40 mg, 36% with 160 mg/80 mg and 12% with placebo, respectively). CDAI, IBD quality of life assessment (IBDQ) and C-reactive protein (CRP) values were also improved in the adalimumab-treated groups. From this trial, the authors concluded that a 160-mg induction dose followed by 80 mg at week 2 was effective in inducing Ruboxistaurin (LY333531) remission . The CLASSIC II study followed patients who achieved remission in the first trial and randomized them to either placebo, or adalimumab 40 mg weekly or every other week. Adalimumab treatment was superior to placebo at 56 weeks (79% remission every other week, 83% weekly) in maintaining a response measured as a 100-point decrease in the CDAI. In addition, most patients were able to discontinue steroids by the end of the trial. In the open-label study of those who did not respond by week 4 in the CLASSIC I trial, only 46% of patients were in remission, suggesting that an early response may predict the likelihood of a sustained response at 56 weeks . Short-term response and remission to adalimumab were documented in the CARE study, which was a large (n = 945) Phase III trial that evaluated the.