Clinical Gastroenterology and Hepatology
Volume 7, Issue 10 , Page 1139, October 2009

Insufficient Evidence to Conclude Whether Anti–Tumor Necrosis Factor Therapy Increases the Risk of Lymphoma in Crohn's Disease

  • Laurent Peyrin–Biroulet, MD, PhD

      Affiliations

    • Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
    • ,
  • Jean–Frederic Colombel, MD

      Affiliations

    • Hopital Claude Huriez, Chu Lille, Lille, France
    • ,
  • William J. Sandborn, MD

      Affiliations

    • Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota

published online 25 May 2009.

Article Outline

 

Dear Editor:

Siegel et al1 reported an increased risk of lymphoma in Crohn's disease patients receiving combination therapy with anti–tumor necrosis factor (TNF) agents and immunomodulators. We believe that no definite conclusions can be drawn from this meta-analysis for the following reasons.

First, only studies with a minimum follow-up of 48 weeks were included.1 Lymphoma might occur during the first year of treatment. Twelve weeks might be a more reasonable inclusion criterion.2 A sensitivity analysis could be performed that excludes short-term trials.

Second, only anti-TNF agents proven effective for Crohn's disease were included. Three other anti-TNF agents (etanercept, onercept, CDP571) have been studied in Crohn's disease.3 Data from these studies should be included to increase statistical power for this rare event.2, 3

Third, lymphoma risk associated with combination therapy with anti-TNF agents and immunomodulators did not differ from that reported with immunomodulators alone, and 10 of 13 patients who developed lymphoma were receiving immunomodulators.1 Because the authors collected patient level data, the influence of immunomodulator use on lymphoma risk should be analyzed.

We found no increased risk of malignancies with anti-TNF therapy in 5356 patients with Crohn's disease.3 Siegel et al1 stated that the major limitation to our study was the lack of true placebo because some patients received induction therapy with an anti-TNF agent. Exclusion of these 6 maintenance trials did not change our results.3

Overall, these 2 meta-analyses do not allow definitive conclusions to be drawn regarding the risk of lymphoma in patients with Crohn's disease receiving anti-TNF therapy.1, 3

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References 

  1. Siegel CA, Marden SM, Persing SH, et al. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis. Clin Gastroenterol Hepatol. 2009;(in press)
  2. Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275–2285
  3. Peyrin-Biroulet L, Deltenre P, de Suray N, et al. Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008;6:644–653

 Conflicts of interest The authors disclose no conflicts.

PII: S1542-3565(09)00451-0

doi:10.1016/j.cgh.2009.05.012

Refers to article:

  • PodcastLinking Article with Gastroenterology Risk of Lymphoma Associated With Combination Anti–Tumor Necrosis Factor and Immunomodulator Therapy for the Treatment of Crohn's Disease: A Meta-Analysis , 27 January 2009

    Corey A. Siegel, Sadie M. Marden, Sarah M. Persing, Robin J. Larson, Bruce E. Sands
    Clinical Gastroenterology and Hepatology August 2009 (Vol. 7, Issue 8, Pages 874-881)

Clinical Gastroenterology and Hepatology
Volume 7, Issue 10 , Page 1139, October 2009