Role of Thiopurine and Anti-TNF Therapy in Lymphoma in Inflammatory Bowel Disease

Division of Research, Kaiser Permanente Northern California, Oakland, 94612, USA.
The American Journal of Gastroenterology (Impact Factor: 9.21). 12/2011; 106(12):2146-53. DOI: 10.1038/ajg.2011.283
Source: PubMed

ABSTRACT The objective of this study was to assess inflammatory bowel disease (IBD) medications in relation to lymphoma risk.
Information on IBD and relevant medications and other utilization was obtained from the Kaiser Permanente IBD Registry, 1996-2009. Lymphoma cases were ascertained from the Kaiser Permanente Cancer Registry. Lymphoma incidence was compared between the IBD cohort and the general Kaiser Permanente population.
Of the 16,023 IBD patients without human immunodeficiency virus followed an average 5.8 years, 43 developed lymphoma. IBD patients with and without lymphoma did not differ with respect to past IBD-related visits, procedures, or tests. The standardized incidence rate ratio (SIRR) for lymphoma among IBD patients with no dispensing of thiopurine or anti-tumor necrosis factor (TNF) was 1.0 (95% confidence interval (CI): 0.96-1.1). Of the 21,282 person-years involving exposure to thiopurine or anti-TNF, 81% involved thiopurine alone; 3%, anti-TNF alone; and 16%, combination therapy. Among patients with thiopurine but not anti-TNF dispensings, the SIRR was 0.3 (95% CI: 0.2-0.4) for past use and 1.4 for current use (95% CI: 1.2-2.7). Among patients with dispensing of anti-TNF (with and without thiopurine), the SIRR was 5.5 for past use (95% CI: 4.5-6.6) and 4.4 for current use (95% CI: 3.4-5.4). The most common lymphoma subtypes were diffuse large B-cell lymphoma (44%), follicular lymphoma (14%), and Hodgkin's disease (12%).
Our study provides evidence that IBD alone is not associated with the risk of lymphoma. Use of anti-TNF with thiopurine and current use of thiopurine alone were associated with increased risk, although the effect of disease severity merits further evaluation.

  • Source
    • "NS Vos et al., 2011 22 SIR 1.0 (95% CI 0.96–1.1) NS Herrinton et al., 2011 41 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The lymphoproliferative disorders (LDs) are a heterogeneous group of at least 70 conditions that result from the clonal proliferation of B, T, and NK cells. Inflammatory bowel disease (IBD)‐associated lymphomas are typically B‐cell LD, while T‐cell or Hodgkin's lymphomas are rare.In IBD patients not on immunosuppression, the risk of LD seems to be similar or slightly higher than the background population risk. Thiopurine therapy is associated with an increased risk: the relative risk is increased four‐ to sixfold and the absolute risk varies between 1 in 4000–5000 for those aged 20–29 to 1 in 300–400 in those over 70. It is difficult to quantify the risk of anti‐ tumor necrosis factor (TNF) therapy alone; however, it appears to be less than for thiopurines alone.There is particular concern regarding the development of post‐transplant‐like LD in those with latent epstein‐barr virus (EBV) infection exposed to immunosuppressives, the occurrence of hepatosplenic T cell lymphoma in patients treated with combination anti‐TNF and thiopurine therapy, and the development of hemophagocytic lymphohistiocytosis in those who acquire a primary EBV or other infections while on immunosuppressive medication. There are currently no guidelines for monitoring EBV (or other virus) status in patients on immunosuppression, although it could be used to monitor those who have a prior history of lymphoma and are about to start a thiopurine or anti‐TNF agent.In discussing the risks of lymphoproliferative disorders associated with agents used for the treatment of IBD, patients can often be reassured that the benefits of such therapy still outweigh the small, but real, risks.
    Journal of Gastroenterology and Hepatology 01/2013; 28(1). DOI:10.1111/jgh.12015 · 3.63 Impact Factor
  • Source
    Gastroenterology and Hepatology 01/2012; 8(1):45-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction of biological agents for the treatment of Crohn’s disease (CD) has led to a transformation of the treatment paradigm. Several biological compounds have been approved for patients with CD refractory to conventional treatment: infliximab, adalimumab and certolizumab pegol (and natalizumab in several countries outside the European Union). However, despite the use of biologics for more than a decade, questions still remain about the true efficacy and the best treatment regimens – especially about when to discontinue treatment. Furthermore, a need for optimizing treatment with biologics still exists, as 20–40% of patients with CD (depending on selection criteria) do not have any relevant response to the current biological agents (i.e. primary failures). A better patient selection might maximize the clinical outcome while minimizing the complications associated with this type of therapy. However, the clinical tools capable of identifying such patients are still unavailable, and the trough level strategy may help the clinician to optimize therapy and to avoid loss of response and/or immunogenicity (i.e. a low but measurable antibody level exists just before the periodic administration of the biological agent). On the other hand, peak levels and average levels should not exceed concentrations associated with increased toxicity. Randomized, controlled studies focusing on trough levels and antibodies towards the biological agent in routine clinical situations may add important pieces to the puzzle for a more rational treatment algorithm of CD patients. In some situations, the risks (i.e. immunogenicity, serious infections and the promotion of neoplasia) may, however, not outweigh the benefits of biological treatment.
    Digestive Diseases 01/2012; 30(s3):121-133. DOI:10.1159/000342738 · 1.83 Impact Factor
Show more