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DOP099. Five-year safety results from the ENCORE registry: Malignancies in patients with Crohn's disease treated with infliximab, standard therapy, or switched from standard therapy to infliximab

G. D'Haens1, W. Reinisch2, J.-F. Colombel3, J. Panes4, S. Ghosh5, C. Prantera6, S. Lindgren7, D.W. Hommes8, Z. Huang9, S. Huyck10, D.K. Chitkara11, 1Academic Medical Center, Inflammatory Bowel Disease Centre, Amsterdam, Netherlands, 2Medical University, Department of Internal Medicine III, Vienna, Austria, 3Icahn School of Medicine at Mount Sinai, Department of Gastroenterology, New York, United States, 4Hospital Clinic I Provincial, Department of Inflammatory Disease, Barcelona, Spain, 5University of Calgary, Department of Medicine, Calgary, Canada, 6AO San Camillo Forlianini, Gastroenterology Operative Unit, Rome, Italy, 7University Hospital MAS, Department of Gastroenterology, Malmö, Sweden, 8University of California Los Angeles, Center for Inflammatory Bowel Diseases, Los Angeles, United States, 9Merck Sharp & Dohme, Department of Epidemiology, Kenilworth, United States, 10Merck Sharp & Dohme, Department of Statistics, Merck Research Laboratories, Kenilworth, United States, 11Merck Sharp & Dohme, Department of Clinical Research, Kenilworth, United States

Background

The risk of malignancy associated with treatments can only be evaluated in large cohorts of patients with long-term follow-up, as available in prospective registries of patients in typical clinical practice. This analysis assessed the risk of lymphoproliferative disorders/malignancies (LPD/M) in patients with Crohn's disease (CD) who received infliximab (IFX) vs standard therapy as part of a 5-year registry.

Methods

The European National Crohn's Observational Registry (ENCORE; NCT00705614) is a prospective, observational safety surveillance registry of patients with CD receiving standard nonbiologic therapy (STD) or IFX or who switched from STD to IFX after enrolment (S2IFX). Enrollment from clinical practices in 9 EU countries occurred from 2003 to 2008; patients were to be followed for 5 years. The incidence of LPD/M was compared among the 3 treatment groups. A multivariate analysis of time to first LPD/M event was conducted to adjust for potential confounders.

Results

Of 2662 patients enrolled, 1121 patients were in the STD group, 1541 in the IFX group, and 298 in the S2IFX group. Follow-up patient-years in these groups were 3750, 6417, and 972, respectively. The incidence of any LPD/M or serious LPD/M was similar in the IFX, STD, and S2IFX groups (Table).

The most common LPD/Ms were basal cell carcinoma (STD, 6 patients [0.5%]; IFX, 5 patients [0.3%]; S2IFX, 0 patients) and breast cancer (STD, 3 patients [0.3%]; IFX, 5 patients [0.3%]; S2IFX, 0 patients). In a multivariate analysis of time to first LPD/M event, adjusting for age and disease duration, IFX was not associated with a significantly increased risk (hazard ratio [HR] for IFX vs STD, 1.44 [95% CI, 0.86–2.42]). Age (continuous) and disease duration (≥6 vs <6 years) were associated with significantly increased risks (HR = 1.05, 95% CI 1.03–1.06 and HR = 2.09, 95% CI 1.22–3.56, respectively). A sensitivity analysis taking into account the timing of the last IFX dose in relation to adverse event onset produced a similar result.

Table: Incidence of selected adverse event (AE) categories by treatment group
 Standard therapy (N = 1121)IFX (N = 1541)Switched to IFX (N = 298)
Any AE, n (%) 724 (64.6) 1300 (84.4) 226 (75.8)
 Events per 1000 person-years (95% CI) 193.1 (179.2, 207.6) 202.6 (191.7, 213.9) 232.6 (203.3, 265.0)
Any serious AE, n (%) 391 (34.9) 792 (51.4) 136 (45.6)
 Events per 1000 person-years (95% CI) 104.3 (94.2, 115.1) 123.4 (115.0, 132.3) 140.0 (117.4, 165.6)
Any LPD/Ms, n (%) 21 (1.9) 49 (3.2) 8 (2.7)
 Events per 1000 person-years (95% CI) 5.6 (3.5, 8.6) 7.6 (5.6, 10.1) 8.2 (3.6, 16.2)
Serious LPD/Ms, n (%) 15 (1.3) 44 (2.9) 6 (2.0)
 Events per 1000 person-years (95% CI) 4.0 (2.2, 6.6) 6.9 (5.0, 9.2) 6.2 (2.3, 13.4)

Conclusion

During 5 years of follow-up in the ENCORE registry, the crude incidence of LPD/M was numerically greater for the IFX group than the STD group. After adjusting for potential confounders, the IFX group did not have a significantly increased risk of LPD/M. The observed differences may be due to differences in disease duration and severity between the groups. Further analyses will be conducted. This study was funded by Merck & Co.