Original articles—alimentary tractRisk of Lymphoma Associated With Combination Anti–Tumor Necrosis Factor and Immunomodulator Therapy for the Treatment of Crohn's Disease: A Meta-Analysis
Section snippets
Data Sources and Searches
A literature search was conducted by using the databases MEDLINE via Ovid (1950–October 2007), EMBASE (1974–2007), and Cochrane Reviews/CENTRAL (1990–2007), and meeting abstracts were searched via Web of Science (1996–2007). The search terms included “Crohn's” and related terms “Infliximab,” “Adalimumab,” “Certolizumab pegol,” and related pharmaceutical names. There were no limits used in our search strategy.
Results of search
Our initial electronic search of MEDLINE identified 644 potentially relevant publications. After eligibility screening by abstract and title, 55 articles were obtained for more detailed review, of which 35 were excluded for reasons shown in Figure 1. A search of Web of Science identified 6 additional abstracts. If meeting abstracts were identified that included more recent and updated information than a previously published article, data from the meeting abstract replaced those of the full
Discussion
Anti-TNF drugs for the treatment of CD appear to be associated with an increased risk of NHL. Although the increased risk is statistically significant when compared with the general population, the absolute risk remains small (6.1 per 10,000 patient-years). When compared with CD patients taking immunomodulators alone, there is a nonstatistically significant increased rate of NHL for those exposed to anti-TNF agents.
The baseline risk of NHL increases with age and is male-predominant.41
Acknowledgments
The authors thank Dr H. Gilbert Welch and Thomas Mead for statistical and search support (Dartmouth Institute for Health Policy and Clinical Practice) and the pharmaceutical companies (Abbott, Centocor, and UCB) and individual authors (L. Biancone, R. Cohen, J. Doumit, S. Hanauer, M. Lemann, V. Pacault, C. Petruzziello, L. Peyrin-Biroulet, L. Rodrigo, B. Sandborn, B. Sands, and O. Schroeder) who supplemented the existing published data to provide further details of their patients.
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Conflicts of interest The authors disclose the following: Dr Siegel has served as a consultant or on a scientific advisory board for Abbott, Elan, and UCB; has received honoraria for speaking from Abbott, P&G, and UCB; and has received grant support from P&G. Dr Sands has served as a consultant or on a scientific advisory board for Abbott, Biogen/IDEC, Bristol-Myers Squibb, Centocor, Elan, Millenium Pharmaceuticals, Novartis Pharmaceuticals, Otsuka America Pharmaceuticals Inc, and UCB; has received honoraria for speaking from Abbott, Schering-Plough, and UCB; and has received grant support from Abbott, Bristol-Myers Squibb, Centocor, Elan, Millenium Pharmaceutical, Novartis Pharmaceuticals and Otsuka America Pharmaceutical Inc. The remaining authors disclose no conflicts.
Funding Dr Siegel is supported by a CCFA career development award and by grant number K23DK078678 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and dose not necessarily represent the official views of the National Institute of Diabetes And Digestive and Kidney Diseases or the National Institute of Health.