Serious events with infliximab in patients with inflammatory bowel disease: a 9-year cohort study in the Netherlands.

BACKGROUND: The tumour necrosis factor-alpha inhibitor infliximab is incorporated in the treatment guidelines for patients with inflammatory bowel disease (IBD). However, concerns about serious adverse events such as infections, malignancies and death do exist.

OBJECTIVE: To evaluate the occurrence of serious events of infliximab during 9 years in a single-centre cohort of patients with IBD.

METHODS: Consecutive patients (>18 years) with a proven diagnosis of IBD who started treatment for IBD with infliximab at our referral centre in the Netherlands, from June 1999 to October 2007, were included. Infusion data were collected prospectively and medical records were reviewed retrospectively. All serious events were recorded and scored in the following categories: events leading to hospitalization, infections, malignancies and death. Severity and relationship to the use of infliximab were assessed for every serious event.

RESULTS: 147 patients (33% male, mean age at first infusion 38 years, standard deviation = 12) received a total number of 1924 infusions (median per patient = 10, range 1-70). A total of 89 patients (61%) were hospitalized during follow-up, involving a total of 300 hospitalizations. Of these, 60 hospitalizations (20%) were considered at least possibly related to the use of infliximab. In 21 hospitalizations, the occurrence of a serious infection was considered at least possibly related to infliximab. Of all hospitalized patients, 70 patients (79%) underwent 139 surgical procedures, of which 70 surgeries (50%) were gastrointestinal related. Nine patients (6%) developed malignancies during follow-up: four colorectal carcinomas, one carcinoid tumour with another primary signet-ring cell carcinoma of the small bowel, one breast cancer, two skin cancers and one superficial melanoma. During follow-up, eight patients (5%) died: six as a result of malignancies, one patient as a result of a complication of short bowel syndrome and one patient due to unknown reasons. Patients who developed malignancies tended to have a longer disease duration than those who did not.

CONCLUSION: Clinicians prescribing biological therapies should be aware of the development of serious events in their patients. Thorough follow-up of all patients during treatment with infliximab is warranted. If infliximab is considered in patients with IBD not responding to conventional treatment, efforts to exclude other possible underlying causes for worsening of symptoms should be made. Careful prescribing and monitoring during follow-up remains necessary.