Original article—alimentary tract
Infliximab for Inflammatory Bowel Disease in Denmark 1999–2005: Clinical Outcome and Follow-Up Evaluation of Malignancy and Mortality

https://doi.org/10.1016/j.cgh.2008.05.010Get rights and content

Background & Aims

Data on safety and long-term follow-up evaluation of population-based cohorts of inflammatory bowel disease (IBD) patients treated with infliximab are sparse. The aim of this article is to describe the use of infliximab in a national Danish population-based IBD cohort during 1999–2005.

Methods

Medical records of all infliximab-treated IBD patients were scrutinized to abstract information on patient demographics, treatment efficacy, and adverse events.

Results

A total of 651 patients (619 with Crohn's disease, 15 with ulcerative colitis, and 17 with colonic IBD type unclassified) received infliximab during 1999–2005. A total of 3351 infusions were administered, with a median of 3 infusions per patient. A positive clinical response was observed in 82.7% (95% confidence interval, 79.9–85.5) of patients. Infusion reactions were observed after 146 of 3351 infusions (4.4%). Significantly fewer infusion reactions were seen in patients also receiving azathioprine or methotrexate (63 of 2079; 3.0%), compared with patients not receiving azathioprine or methotrexate (83 of 1272; 6.5%) (P < .0001). Severe adverse events were observed after 112 of 3351 infusions (3.3%) in a total of 95 patients (14.6%). Four patients developed cancer versus 5.9 expected (standardized incidence ratio, 0.7; 95 confidence interval, 0.2–1.7) and 13 patients died versus 6.9 expected (standardized mortality ratio, 1.9; 95% confidence interval, 1.0–3.2). Two deaths caused by infections were possibly related to infliximab.

Conclusions

Infliximab seemed effective in IBD and generally was well tolerated. However, rare but severe adverse events occurred, and patients receiving infliximab therefore should be selected carefully and monitored closely. No lymphomas and no increased risk of cancer were observed.

Section snippets

Patient and Background Population

In Denmark, infliximab is administered only to hospitalized patients or in hospital-based outpatient settings in accordance with the National Board of Health. To identify all IBD patients treated with infliximab in Denmark between January 1, 1999, and January 1, 2005, we contacted all Gastroenterology Departments. The combination of free hospital care in Denmark, administration of infliximab limited to few Gastroenterology Departments nationwide, close research collaboration between these

Patient Characteristics

In all, 23 departments reported the use of infliximab in patients with IBD during 1999–2005. Medical records were available for 651 of 670 (97.2%) IBD patients (619 with CD, 15 with UC, and 17 with colonic IBD type unclassified (IBDU). A total of 385 patients (59%) were females and 64 (10%) were children younger than 18 years of age, and 23 (4%) were younger than age 15. The median age at first infusion was 31.6 years (range, 9.7–92.4 y). Disease duration before the first infusion was a median

Discussion

In this population-based national cohort study of patients with IBD, infliximab was used both for induction, maintenance treatment, and on-demand treatment. Efficacy was higher in CD and UC than in IBDU. The frequency of infusion reactions was reduced significantly by concomitant treatment with azathioprine/methotrexate, but not by treatment with steroids/paracetamol/antihistamine. The frequency of severe adverse events (such as pneumonia, sepsis, and demyelinization) was 3.3%. No increased

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    Dr Bendtsen and Dr Munkholm are members of an advisory board for Schering-Plough, Denmark, and Dr Wewer and Dr Caspersen have received travel grants and payment for oral presentations from Schering-Plough. The present study has received an unrestricted grant from Schering-Plough, Denmark, as well as financial support from the Vibeke Binder & Poul Riis' Foundation and the Pia Munkholm's Foundation.

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