Volume 7, Issue 8 , Pages 874-881, August 2009
Risk of Lymphoma Associated With Combination Anti–Tumor Necrosis Factor and Immunomodulator Therapy for the Treatment of Crohn's Disease: A Meta-Analysis
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.
Abbreviations used in this paper: ADA, adalimumab, CD, Crohn's disease, CI, confidence interval, CTZ, certolizumab pegol, IFX, infliximab, 6MP, 6-mercaptopurine, NHL, non-Hodgkin's lymphoma, RCT, randomized controlled trial, SD, standard deviation, SEER, Surveillance, Epidemiology & End Results, SIR, standardized incidence ratio, TNF, tumor necrosis factor
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.
PII: S1542-3565(09)00052-4
doi:10.1016/j.cgh.2009.01.004
© 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
Volume 7, Issue 8 , Pages 874-881, August 2009
