Article

Risk of Lymphoma Associated With Combination Anti-Tumor Necrosis Factor and Immunomodulator Therapy for the Treatment of Crohn's Disease: A Meta-Analysis

Dartmouth-Hitchcock IBD Center and Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, Massachusetts, USA.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association (Impact Factor: 6.53). 08/2009; 7(8):874-81. DOI: 10.1016/j.cgh.2009.01.004
Source: PubMed

ABSTRACT 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.
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.
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).
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.

1 Follower
 · 
108 Views
  • Source
    • "Author manuscript; available in PMC 2013 January 01. $watermark-text $watermark-text $watermark-text $watermark-text $watermark-text $watermark-text Table 1 Model Input Estimates (Base Case) for Event Probabilities Event Monotherapy Combination therapy Source Remission 0.38 0.47 SONIC week 50 a,4 Response b 0.036 0.030 SONIC week 50 a,4 SAE c 0.24 0.15 SONIC week 54 4 Serious infection d 0.049 0.039 SONIC week 54 4 Lymphoma d 0.0004 0.0006 Kandiel et al, 7 2005; Siegel et al, 5 2009 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The Study of Biologic and Immunomodulator-Naïve Patients With Crohn's Disease (SONIC) showed that combination therapy with infliximab and azathioprine (IFX/AZA) is more effective than treatment with IFX alone. Numbers and types of adverse events were roughly equivalent among groups, although enrollment was limited, so it was not clear how rare adverse events might affect overall outcomes in practice. We sought to define the frequency at which a rare adverse event would have to occur for the risks of combination therapy to outweigh the benefits of treatment. We constructed a decision model to compare the risks and benefits of IFX/AZA with IFX monotherapy. Model parameters were taken from SONIC and other published literature. The base-case analysis was patients with active Crohn's disease who are naïve to both medications (similar to those in SONIC) who were treated for 1 year. We used sensitivity analyses to determine the thresholds at which the risks of side effects from IFX/AZA outweigh its benefits. During 1 year, the benefits of IFX/AZA would outweigh the risks, unless serious infections occurred in 20% or more of the population or lymphoma in 3.9% or more. These thresholds are 5-fold and 65-fold higher than base-case estimates, respectively. On the basis of data from 1 year of SONIC, the combination of IFX/AZA was more effective than IFX alone in patients with Crohn's disease who are naïve to either drug. For the risks of combination therapy to outweigh the benefits in this time frame, the incidence of serious adverse events would have to be higher than seems clinically realistic.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2011; 10(1):46-51. DOI:10.1016/j.cgh.2011.09.017 · 6.53 Impact Factor
  • Source
    • "The risk associated with methotrexate seems lower, although the data are scarce and come from settings other than IBD. Likewise, anti-TNFa agents are usually combined with thiopurines in IBD, meaning that their possible role is difficult to individualize [8]. The recently identified risk of hepatosplenic T cell lymphoma in young male IBD patients co-treated with anti- TNFa and thiopurines is low and does not appear as associated with EBV infection [9]. "
    Journal of Crohn s and Colitis Supplements 04/2010; 4(1):14-15. DOI:10.1016/S1873-9954(10)70023-9
  • Radiographics 33(7):1863. · 2.73 Impact Factor
Show more

Preview

Download
0 Downloads
Available from