Original article
Serious Infections and Mortality in Association With Therapies for Crohn’s Disease: TREAT Registry

https://doi.org/10.1016/j.cgh.2006.03.002Get rights and content

Background & Aims: Long-term safety data for infliximab and other therapies in Crohn’s disease (CD) are needed. Methods: We prospectively evaluated patients for prespecified safety-related outcomes. Results: As of August 2004, 6290 patients were enrolled; 3179 received infliximab (5519 patient-years), 87% of whom received at least 2 infusions, and 3111 received other therapies (6123 patient-years). The mean length of follow-up evaluation was 1.9 years. More infliximab-treated patients had moderate-to-severe (30.8% vs 10.3%) or severe-fulminant (2.5% vs .6%) CD, and had surgical (17.5% vs 13.8%) or medical (14.4% vs 9.1%) hospitalizations in the previous year. More patients were taking prednisone (27.4% vs 16.1%), immunomodulators (49.4% vs 32.2%), or narcotic analgesics (9.8% vs 5.4%) when compared with those receiving other therapies (P < .001, all comparisons). The mortality rates were similar for infliximab- and non–infliximab-treated patients (.53 per 100 patient-years vs .43; relative risk, 1.24; 95% confidence interval [CI], .73–2.10). In multivariate logistic regression analysis, only prednisone was associated with an increased mortality risk (odds ratio [OR], 2.10; 95% CI, 1.15–3.83; P = .016). Although the unadjusted analysis showed an increased risk for infection with infliximab use, multivariate logistic regression analysis suggested that infliximab was not an independent predictor of serious infections (OR, .99; 95% CI, .64–1.54). Factors independently associated with serious infections included prednisone use (OR, 2.21; 95% CI, 1.46–3.34; P < .001), narcotic analgesic use (OR, 2.38; 95% CI, 1.56–3.63; P < .001), and moderate-to-severe disease activity (OR, 2.11; 95% CI, 1.10–4.05; P = .024). Conclusions: Mortality rates were similar between infliximab- and non–infliximab-treated patients. The increased risk for serious infection observed with infliximab likely was owing to disease severity and prednisone use.

Section snippets

Study Design

The TREAT Registry is a prospective, observational, multicenter, long-term registry of North American patients with CD. The registry was initiated in 1999 to evaluate the clinical safety outcomes of various treatment regimens, including infliximab, in the management of CD. Approximately 350 gastroenterologists from both community-based and academic practice settings were each to enroll up to 150 patients for a target enrollment of at least 5000 patients. Most physicians were identified from the

Results

Through August 2004, 6290 CD patients from 212 centers were enrolled from both community (82%) and academic (18%) centers. Most patients were female (58%) and Caucasian (89%), with an average age of 43 ± 14.7 years. The population was distributed almost equally between those who had been treated with infliximab (N = 3179, 50.5%) and those who had not. More than 85% of patients treated with infliximab had received at least 2 infusions. Among patients who received infliximab, a median of 5

Discussion

This is the first report from the TREAT Registry, a large, prospective, observational research program designed to address the long-term safety of medications, including infliximab, for the treatment of CD. After adjustment for confounding factors including disease severity and the use of other medications, the risk for serious infection or death with infliximab use was similar to that observed with the use of conventional immunomodulators, and was not higher than the overall incidence of

Conclusions

Because CD is a chronic, potentially debilitating disease requiring ongoing treatment, physicians must consider the benefit/risk profiles of all therapies. Data from the TREAT Registry indicate that the risks for serious infection and death associated with infliximab are similar to those of conventional immunomodulators over 2 years of follow-up evaluation. Possible factors implicated with a significantly increased risk for serious infections include the use of prednisone, the use of narcotic

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1

Gary R. Lichtenstein has received honorarium and research funding from Centocor, the manufacturers of infliximab; honorarium from Prometheus; honorarium from Salix, the manufacturers of azathioprine; and honorarium from Astra Zeneca, the manufacturers of Budesonide.

2

Michelle L. Pritchard is employed by Ovatich Research Group, a company that receives funding from Centocor Inc.

3

William J. Sandler has received research support and is a Consultant for Centocor, and has participated in CME events indirectly sponsored by Centocor.

4

Bruce A. Salzberg is on the Speakers Bureau for Centocor.

5

Robert H. Diamond is employed by Centocor.

6

Donny M. Chen is a Consultant for Centocor.

7

Russell D. Cohen has received research grants and is a consultant for Centocor, and is a stockholder in Johnson Johnson.

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