Drug Therapies and the Risk of Malignancy in Crohn's Disease: Results From the TREAT™ Registry

The American Journal of Gastroenterology (Impact Factor: 10.76). 01/2014; 109(2). DOI: 10.1038/ajg.2013.441
Source: PubMed


We assessed potential associations between malignancy and antitumor necrosis factor therapy in patients with Crohn's disease (CD), as this relationship is currently poorly defined.

Utilizing data from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT™) Registry, a prospective cohort study examining long-term outcomes of CD treatments in community and academic settings, influences of baseline patient/disease characteristics and medications were assessed by survival analysis and multivariate models. Standardized incidence ratios and exact 95 % confidence intervals were determined as the ratio of events observed (TREAT) vs. expected (general population of USA).

As of 23 February 2010, 6,273 CD patients (infliximab during registry=3,420 (during or within 1 year before registry=3,764); other-treatments-only: 2,509), were enrolled and, on average, had been followed for 5.2/7.6 years, respectively, for all/currently active patients. Crude cancer incidences were similar between infliximab- and other-treatments-only-exposed patients. Multivariate Cox regression analysis demonstrated that baseline age (hazard ratio (HR)=1.59/10 years; P<0.001), disease duration (HR=1.64/10 years; P=0.012), and smoking (HR=1.38; P=0.045) but neither immunosuppressive therapy alone (HR=1.43; P=0.11), infliximab therapy alone (HR=0.59; P=0.16), nor their combination (HR=1.22, P=0.34) were independently associated with the risk of malignancy. When compared with the general population, no significant increase in incidence was observed in any malignancy category. In an exposure-based analysis, use of immunosuppressants alone (odds ratio=4.19) or in combination with infliximab (3.33) seemed to be associated with a numerically, but not significantly, greater risk of malignancy than did treatment with infliximab alone (1.96) relative to treatment with neither.

In the TREAT Registry, age, disease duration, and smoking were independently associated with increased risk of malignancy. Although results for immunosuppressant use were equivocal, no significant association between malignancy and infliximab was observed.

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    ABSTRACT: Crohn's disease is a chronic, progressive and disabling condition. New therapeutic goals have emerged in Crohn's disease such as the need to look beyond symptoms by achieving mucosal healing that is known to be associated with better outcomes. Anti-TNF (Tumor Necrosis Factor) therapy is the most potent drug class to induce and maintain mucosal healing in Crohn's disease. Recent evidence indicates that the efficacy profile of thiopurines has been overestimated while the increased risk of malignancies (lymphoma, non-melanoma skin cancers, myeloid disorders) has been underestimated. Methotrexate is well-tolerated, but its potential for disease modification is unknown. Achieving mucosal healing in patients with early Crohn's disease might be the best way to change disease course and patients' life. In 2014, anti-TNF treatment should be the first-line therapy in patients with Crohn's disease who suffer from severe and/or complicated disease and in those with poor prognostic factors. In the remaining patients, a rapid step-up approach based on a tight monitoring is recommended.
    No preview · Article · Jun 2014 · Baillière&#x027 s Best Practice and Research in Clinical Gastroenterology
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    ABSTRACT: Background Therapeutic objectives are currently evolving in inflammatory bowel diseases (IBD) from control of symptoms towards improvement of long-term disease outcomes. In patients achieving remission, safety concerns – infections or neoplasia – and economic issues are prompting de-escalation strategies.AimTo give a complete overview of studies on de-escalating therapy in IBD.MethodsA structured search in Pubmed, the Cochrane Library and EMBASE was performed using defined key words (inflammatory bowel diseases, Crohn's disease, ulcerative colitis, immunosuppressants, azathioprine, methotrexate, anti-TNF, infliximab, adalimumab, de-escalation, dose reduction, cessation, stopping, withdrawal), including full text articles and abstracts in English language.ResultsEleven studies were identified, investigating cessation of immunosuppressants (IS) and/or anti-TNF treatments. Patients exposed to a combination of IS and anti-TNF have an increased risk for infections, especially due to opportunistic agent, without any clear signal for associated cancers when compared to those receiving single therapy. In patients receiving IS alone, relapse rate at 12 months following IS cessation is close to 20% and 30% in Crohn's disease (CD) and ulcerative colitis (UC) respectively. There is no study specifically evaluating anti-TNF treatment withdrawal in case of scheduled anti-TNF monotherapy in IBD. In patients receiving combination therapy with IS and infliximab (IFX) for at least 6 months, relapse rate of IFX failure following IS cessation is near to 20% at 24 months and seems to be similar in patients who maintained combination therapy. In case of anti-TNF therapy, cessation in CD patients in combo-therapy proportion of relapse is high, close to 40% and 50% over 1 year and 2 years respectively. Regarding higher risk of adverse events, some special situations – young males, pregnancy and elderly – should be managed specifically and de-escalating treatment considered.Conclusions De-escalating treatment strategy should be mainly considered in patients with high risk of severe adverse events and low relapse risk (patients in deep remission) after drug withdrawal. For these reasons, cessation of anti-TNF treatment and/or immunosuppressants should be a case by case decision in highly selected patients.
    Preview · Article · Jun 2014 · Alimentary Pharmacology & Therapeutics
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