BIOLOGIC AGENTS Infliximab Infliximab (Remicade? Centocor, Malvern PA) is a chimeric (75% mouse/25% human) anti-TNF�� monoclonal antibody; TNF�� mediates multiple newsletter subscribe pro-inflammatory processes central to the pathogenesis of IBD. The first study that defined efficacy of infliximab in the treatment of active CD randomized patients with moderate-severe, medically-refractory, disease to receive a single infusion of placebo or 5, 10 or 20 mg/kg of infliximab. Seventeen percent, 81%, 50% and 64% of patients respectively had a response (CDAI decrease �� 70 points) at wk 4 (P < 0.001 for all infliximab patients vs placebo). Overall, 33% of all infliximab patients compared to 4% of placebo achieved remission at wk 4 (P = 0.005). While significantly more infliximab patients maintained a response at 12 wk, 37% had relapsed, suggesting that a single dose was insufficient[95].

Those patients who had an initial response to the single infusion were subsequently randomized to receive continued dosing with 10 mg/kg every 8 wk or placebo. After 44 wk, 53% of the infliximab group were in remission compared to 20% of the placebo group (P = 0.013)[96]. The ACCENT I study expanded on the potential maintenance benefits of infliximab after an initial response. In the trial, 573 patients received a 5 mg/kg intravenous (IV) infusion of infliximab at wk 0, after which they were assessed for clinical response by CDAI (decrease in score �� 70 and a 25% reduction in total score).

Three hundred and thirty five patients (58%) met this criterion and were randomized to one of three treatment groups: placebo at wk 2 and 6 and then every 8 wk (group I ), infliximab 5 mg/kg on the same schedule (group II) or 5 mg/kg at wk 2 and 6 followed by 10 mg/kg every 8 wk (group III). Treatment was continued for 46 wk. At wk 14 or later, patients in all groups who initially had response and then worsened were allowed GSK-3 to cross over to active episodic retreatment (infliximab 5, 10 or 15 mg respectively for groups I , II, and III given on an ��as needed�� basis). At wk 30, 21% of patients in groupI, 39% in group II (P = 0.003) and 45% in group III (P = 0.0002) respectively were in remission, while median time to loss of response was reported as 19, 38 (P = 0.002) and more than 54 wk (P = 0.0002) respectively. Significantly more patients in groups II and III combined (29%) compared with group I (9%) had discontinued steroids at wk 54, and fewer hospitalizations and surgeries related to CD occurred in the maintenance therapy groups. There were no differences in serious adverse events between the three groups[97].