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Meta-Analysis
. 2009 Aug;7(8):874-81.
doi: 10.1016/j.cgh.2009.01.004. Epub 2009 Jan 24.

Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis

Corey A Siegel  1 , Sadie M Marden, Sarah M Persing, Robin J Larson, Bruce E Sands
Affiliations
Meta-Analysis

Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis

Corey A Siegel et al. Clin Gastroenterol Hepatol. 2009 Aug.

Abstract

Background & aims: Although anti-tumor necrosis factor (TNF) therapy can effectively treat Crohn's disease (CD), there is concern that it might increase the risk of non-Hodgkin's lymphoma (NHL). A meta-analysis was performed to determine the rate of NHL in adult CD patients who have received anti-TNF therapy and to compare this rate with that of a population-based registry and a population of CD patients treated with immunomodulators.

Methods: MEDLINE, EMBASE, Cochrane Collaboration, and Web of Science were searched. Inclusion criteria included randomized controlled trials, cohort studies, or case series reporting on anti-TNF therapy in adult CD patients. Standardized incidence ratios (SIR) were calculated by comparing the pooled rate of NHL with the expected rate of NHL derived from the Surveillance Epidemiology & End Results (SEER) database and a meta-analysis of CD patients treated with immunomodulators.

Results: Twenty-six studies involving 8905 patients and 21,178 patient-years of follow-up were included. Among anti-TNF treated subjects, 13 cases of NHL were reported (6.1 per 10,000 patient-years). The majority of these patients had previous immunomodulator exposure. Compared with the expected rate of NHL in the SEER database (1.9 per 10,000 patient-years), anti-TNF treated subjects had a significantly elevated risk (SIR, 3.23; 95% confidence interval, 1.5-6.9). When compared with the NHL rate in CD patients treated with immunomodulators alone (4 per 10,000 patient-years), the SIR was 1.7 (95% confidence interval, 0.5-7.1).

Conclusions: The use of anti-TNF agents with immunomodulators is associated with an increased risk of NHL in adult CD patients, but the absolute rate of these events remains low and should be weighed against the substantial benefits associated with treatment.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Flow diagram of the studies identified in search, and reasons for study exclusion.
Figure 2
Figure 2
Heterogeneity among the studies. The relative risk of NHL (compared with SEER) is plotted against the absolute rate per 10,000 patient-years for each study. Twenty of the 26 studies did not have any reported cases of lymphoma. The outlier study with the highest rate is Ljung et al.
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