Original Article
Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease

https://doi.org/10.1016/j.gie.2005.08.011Get rights and content

Background

The endoscopic substudy of the ACCENT I (A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen) Crohn's disease trial examined the effects of infliximab on mucosal inflammation and mucosal healing, and assessed their impact on outcomes.

Design

ACCENT I was a randomized, double-blind, parallel group study.

Setting

This study took place at multiple centers in North America, Europe, and Israel.

Main Outcome Measurements

Ileocolonoscopic examinations were performed at weeks 0, 10, and 54. Complete mucosal healing was defined as the absence of all mucosal ulcerations. The end point of principal interest was the proportion of patients randomized as responders with mucosal healing at week 10. The proportion of responders who demonstrated mucosal healing at week 54 or at both weeks 10 and 54 is also summarized. Changes in Crohn's disease endoscopic index of severity (CDEIS) scores from baseline to week 10 and 54 were calculated for all patients in this substudy.

Results

Complete mucosal healing by week 10 occurred in significantly more week 2 responders who had received 3 doses of infliximab compared with a single dose (31% vs. 0%, p = 0.010). A significantly higher proportion of week 2 responders in the combined scheduled maintenance group had complete mucosal healing at week 54 compared with the episodic group (50% vs. 7%, p = 0.007). The results for all patients are consistent with those for week 2 responders only. Significantly greater improvement in the CDEIS occurred with scheduled maintenance compared with episodic treatment at week 10 (p ≤ 0.001) and week 54 (p = 0.026). Notably, no strong relationship between clinical remission and complete mucosal healing was found. Overall, mucosal healing appeared to correlate with fewer hospitalizations, although these results were not statistically significant.

Conclusions

Scheduled infliximab maintenance therapy resulted in more improvement in mucosal ulceration and in higher rates of mucosal healing. There was a numerical trend for patients with better mucosal healing to have a lower rate of Crohn's disease-related hospitalizations.

Section snippets

Patients

The ACCENT I study was a multicenter, randomized, double-blind study conducted at 55 sites in North America, Europe, and Israel. A total of 100 consecutive patients at selected study sites in North America and Europe had the opportunity to participate in this endoscopic substudy. The institutional review boards at the participating sites approved both the primary and endoscopy substudy protocols. Participation in the endoscopic substudy required written patient informed consent.

Eligible

Patient disposition, baseline characteristics

A summary of patient disposition for those evaluated for mucosal healing is provided in Figure 1. As shown, 99 patients were randomized and underwent endoscopic examination at week 0. Seventeen patients did not have confirmed ulceration in their colon or terminal ileum at baseline, and one patient withdrew consent. Therefore, 81 of 99 patients (82%) who were randomized demonstrated mucosal ulceration at baseline. Six patients (3 episodic and infliximab maintenance therapy, each) did not have

Discussion

The results of this study demonstrated that scheduled maintenance therapy with infliximab was significantly more likely than episodic treatment to induce complete mucosal healing and decrease endoscopic evidence of inflammation. By week 10, patients who received scheduled maintenance treatment had more than twice the improvement in CDEIS as that exhibited by patients in the episodic group. The greater benefit of scheduled treatment was maintained through week 54, with patients in the combined

Acknowledgments

The authors wish to thank Marion A. Blank, PhD, for her critical review of this manuscript and Mary Ann Thomas, RN, BSN, and Mary Whitman, PhD, for their writing and editorial assistance.

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