Serious infections, neoplasms and mortality in association with therapies for Crohn's
disease: preliminary results from the ENCORE registry
D.W. Hommes1, J. Panés2, J.F. Colombel3, G. D'Haens4, P. Rutgeerts5, A. Ekbom6,
U. Barai7, H. van Hoogstraten7, M. Wiekowski7, C. Antoni7.
1
Leids Universitair Medisch Centrum, Leiden, Netherlands; 2Hospital Clinic
Provincial, Barcelona, Spain; 3CHRU Lille, Service d'Hépato-Gastroentérologie,
Cedex, Lille, France; 4Imeldaziekenhuis, Gastro-enterologie, Bonheiden, Belgium;
5
University of Leuven, Division of Gastroenterology, Leuven, Belgium; 6Karolinska
Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm,
Sweden; 7Schering-Plough Research Institute, Kenilworth, NJ, United States
Aim: To collect long-term safety data on patients with Crohn' s disease treated with
Infliximab (IFX) or Non-Biologic Therapy (NBT). Methods: This is a post-marketing,
observational, non-randomized, parallelgroup, safety surveillance registry of CD
patients treated with IFX or NBT. The incidence of treatment-emergent adverse
events was determined. As of May 2007, a total of 2008 subjects were enrolled: 1166
patients receiving IFX treatment (63% female; mean age 36.4±12.89 years); 842
patients receiving NBT (61% female; mean age 37.5±12.67 years). The median length
of follow-up was 13.2 months in the IFX group and 12.7 months in the NBT group. A
multivariate Cox's proportional Hazard model was fitted to time to first serious
infection, with treatment and prognostic variables based on demographics and disease
characteristics in the model. In order to limit the number of variables, prognostic
variables were selected based on univariate models (p=0.10). Univariate models
included age (continuous), gender, smoking status, draining fistula, disease severity,
disease duration, involvement of ileum, and prednisone. Results: At baseline, IFXtreated patients, when compared to the NBT group, had a more severe disease activity
index (mean Harvey- Bradshaw index of 8.4±5.55 vs. 6.3±5.16), a higher incidence of
draining fistulae (23.3% compared to 9.4%), a longer disease duration (mean time
since initial diagnosis 9.1±8.97 vs. 8.0±8.62 years) and increased medical
hospitalizations in the 6 months prior to their baseline evaluation (42.8% vs. 37.9%).
In addition, more patients in the IFX group were taking narcotic analgesics (8.7% vs.
5.8%), antibiotics (21.5% vs. 13.2%), azathioprine (57.1% vs. 50.4%), 6mercaptopurine (5.5% vs. 4.0%), and methotrexate (10.9% vs. 5.0%) when compared
to the NBT group. Conversely, patients in the IFX group received less corticosteroid
treatment at baseline (60% IFX vs. 66% NBT). The multivariate model, which
adjusted treatment effect for selected prognostic variables, showed treatment with IFX
or NBT was not an independent predictor of serious infection (p=0.30). Factors that
were independently associated with serious infection included age (p=0.026), disease
severity (p=0.024) and prednisone use (p=0.009).
Conclusions: A Safety Analysis of IFX in CD confirms that corticosteroids, but not
IFX, pose an increased risk for serious infection. Additionally, age and severity of
disease were associated with occurrence of serious infections.