Clinical Gastroenterology and Hepatology
Volume 7, Issue 11 , Page 1257, November 2009

Reply

  • Sarah Caspersen, MD

      Affiliations

    • Department of Medical Gastroenterology, University of Copenhagen, Herlev, Denmark
    • ,
  • Christian Mortensen, MD

      Affiliations

    • Department of Medical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark
    • ,
  • Lene Riis, MD

      Affiliations

    • Department of Medical Gastroenterology, University of Copenhagen, Herlev, Denmark
    • ,
  • Tine Jess, MD

      Affiliations

    • Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark
    • ,
  • Flemming Bendtsen

      Affiliations

    • Department of Medical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark

published online 23 September 2009.

Article Outline

 

The following reply refers to a letter to the editor (de Vries HE, Van Oijen MGH, de Jong DJ. Safety of infliximab in inflammatory bowel disease needs to be debated. Clin Gastroenterol Hepatol 2009;7:603–604) published in the May 2009 issue of Clinical Gastroenterology and Hepatology.

We thank you for the opportunity to respond to the letter by de Vries et al regarding our results on long-term safety of infliximab treatment in Denmark.1

We fully agree with de Vries et al that the continued vigilance of the safety of anti–tumor necrosis factor (TNF)–α therapy in IBD is warranted and welcome the discussion of interpretation of long-term safety data.

As pointed out by de Vries et al, we concluded that infliximab was generally well-tolerated, despite the occurrence of adverse events in a high proportion of patients. As in the interesting study published by de Vries et al,2 our design does not include a control group, and we were unable to accurately distinguish between background symptoms, adverse events related to concomitant therapy, and symptoms related to infliximab infusions. Accordingly, we chose to report any adverse event possibly related to infliximab, including events that did not cause clinical intervention or hospitalization, without doing retrospective evaluations of causality. We respectfully acknowledge the opinion that even more adverse events would have been registered if this had been a clinical trial, and we would like to add that we have seen very high rates of adverse events in placebo-treated groups in clinical trials as well. Tolerability of a therapy, in our opinion, is dependent mainly on the risk of severe adverse events that might have clinical consequences such as hospitalization, hence leading to cessation of the therapy. The number of patients (14.6%) experiencing what we defined as severe adverse events during infliximab treatment in our study is considerable and certainly of interest for clinicians and patients for whom infliximab treatment is planned. However, the risk of even serious adverse events must be weighed against the potential therapeutic benefit of any drug.

Regarding the cancer rate in the Danish cohort, which is lower than the rates reported in the mentioned studies,2, 3, 4 the variations are most likely solely due to differences in follow-up time, but only longer observation of our cohort can reveal whether additional cancers were under development.

We compared our patients' cancer and mortality risk with the risk of the Danish background population, finding no excess risk of cancer and, as expected, a slightly increased mortality in patients with Crohn's disease. We would certainly have preferred a control group of well-matched infliximab-untreated IBD patients for comparison, as mentioned in our study's discussion and as presented in the impressive study by Fidder et al,3 and this will be the aim of future studies from our group as well.

Back to Article Outline

References 

  1. Caspersen S, Elkjaer M, Riis L, et al. Infliximab for inflammatory bowel disease in Denmark 1999–2005: clinical outcome and follow-up evaluation of malignancy and mortality. Clin Gastroenterol Hepatol. 2008;6:1212–1217
  2. de Vries HS, van Oijen MG, de Jong DJ. Serious events with infliximab in patients with inflammatory bowel disease: a 9-year cohort study in the Netherlands. Drug Saf. 2008;31:1135–1144
  3. Fidder HH, Schnitzler F, Ferrante M, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single center cohort study. Gut. 2009;58:501–508
  4. Lees CW, Ali AI, Thompson AI, et al. The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years, follow-up. Aliment Pharmacol Ther. 2009;29:286–297

 Conflicts of interest The authors disclose the following: Dr Caspersen has received travel grants and payment for oral presentations from Schering-Plough, Denmark. Dr Bendtsen is a member of an advisory board for Schering-Plough, Denmark. The remaining authors disclose no conflicts.

PII: S1542-3565(09)00909-4

doi:10.1016/j.cgh.2009.09.016

Refers to article:

  • Safety of Infliximab in Inflammatory Bowel Disease Needs to Be Debated , 29 December 2008

    Hilbert S. de Vries, Martijn G.H. Van Oijen, Dirk J. de Jong
    Clinical Gastroenterology and Hepatology May 2009 (Vol. 7, Issue 5, Pages 603-604)

Clinical Gastroenterology and Hepatology
Volume 7, Issue 11 , Page 1257, November 2009