Inflammatory bowel diseases (IBD) and their treatments, particularly immunosuppressive drugs, increase risk of infections and cancers. However, by promoting mucosal healing, these agents reduce risks of infections related to intestinal lesions, malnutrition, intravenous devices, and IBD surgeries and reduce risk of cancers associated with chronic mucosal inflammation. Laurent Beaugerie and Julien Kirchgesner discuss the risks and benefits of IBD therapies in a review article in the February issue of Clinical Gastroenterology and Hepatology.
Corticosteroids increase the risk of vascular thromboembolic events, yet other immunosuppressive drugs that induce remission in patients with IBD could decrease the incidence of cardiovascular events attributable to systemic inflammation and IBD-related hospitalizations and/or surgeries, the authors state.
The nature and magnitude of the risks of infections and cancers vary with immunosuppressive drug class and patient sex and age. For example, thiopurines increase risk of viral infections that might be fatal in young patients, whereas tumor necrosis factor antagonists increase risk of bacterial and intracellular infections that can be fatal in patients of any age, but particularly in older patients.
Patients with IBD exposed to thiopurines have an increased risk of nonmelanoma skin cancers, and patients exposed to anti-TNF agents are at increased risk of melanoma. Patients with IBD without chronic intestinal inflammation have no increase in risk of colorectal cancer, anal cancer, or cholangiocarcinoma compared with matched individuals in the general population. In contrast, risk of digestive tract cancers, including oral cancer, is increased when digestive organs are chronically inflamed.
Population-based studies revealed up to a 3-fold increase risk for venous thromboembolism (VTE) in patients with IBD compared with non-IBD control subjects, with the highest risks reported in patients with IBD flare, outside the hospital and without thromboprophylaxis. Patients with IBD exposed to systemic corticosteroids also have an increased risk of VTE , but a meta-analysis found a 70% decrease in risk of VTE in patients with IBD treated with anti-TNF agents compared with corticosteroids. IBDs also increase the risk of death from cardiovascular disease—particularly in women. Anti-TNF agents and thiopurine have been found to reduce the incidence of acute arterial events in patients with IBD.
Beaugerie and Kirchgesner understand that it is difficult for clinicians to assess the benefits and risks of IBD immunosuppressive therapies. Treatment benefits are reported in randomized controlled trials, and treatment risks or indirect treatment benefits (such as chemoprevention, cardiovascular protection) are reported in observational studies. However, clinical decision models, such as the Markov model, are used to evaluate risk vs benefits of treatments for IBD. The authors discuss special situations that require specific assessments of this balance, such as older age, pregnancy, or previous cancers.
Beaugerie and Kirchgesner state that models to assess the benefit to risk ratio of long-term use of immunosuppressive drugs for patients with IBD should be adapted based on patients’ age, sex, and IBD phenotype, to properly guide patient management. The decision-making process should begin with a clear explanation of treatment risks and then integrate the patient’s emotional perception of risks.
The authors conclude that for patients with severely active IBD, the risks of IBD complications are greater than the risks of complications from IBD drugs, on a short-term basis. In contrast, in patients with sustained deep remission thanks to immunosuppressive therapy, the long-term cumulative risks of IBD drugs may outweigh the risks associated with disease relapse. Long-term risks of immunosuppressive drugs are also age- and sex-dependent. Personalized assessment of the benefit to risk balance of immunosuppressive IBD drugs is required to select the best treatment strategy for each patient with IBD.