Adverse events in IBD: to stop or continue immune suppressant and biologic treatment

Abstract

Crohn’s disease and ulcerative colitis affect an increasing number of patients. A variety of medical options exist for the treatment of these diseases including immune suppressants and biologic therapies. Unfortunately, these agents are associated with adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. This review discusses adverse events associated with azathioprine, mercaptopurine, and methotrexate as well as anti-TNF-α and anti-integrin antibodies. In addition, adverse events associated with combination therapy are discussed as are clinical scenarios in which it may be reasonable to discontinue or de-escalate drug therapy. It is the responsibility of the treating gastroenterologist to effectively communicate the benefits and risks of therapy with patients; this review offers strategies that may assist providers in communicating risk with patients in addition to offering our perspective on whether modification or cessation of therapy can be considered.

Keywords::

• adalimumab
• azathioprine
• certolizumab pegol
• Crohn’s disease
• inflammatory bowel disease
• infliximab
• mercaptopurine
• methotrexate
• natalizumab
• ulcerative colitis

Financial & competing interests disclosure

LP McLean was supported by NIH grant T32 DK-067872. RK Cross was supported by AHRQ grant R01 HS-018975. RK Cross has received educational and research grants from Abbvie and Janssen, has participated in advisory boards and consulting for Abbvie and Janssen and receives honoraria for disease state awareness lectures from both Abbvie and Janssen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Crohn’s disease and ulcerative colitis are chronic inflammatory conditions in which the immune system inappropriately targets the gastrointestinal tract.

• Immune suppressants and biologic therapy are effective treatments for patients with moderate-to-severe Crohn’s disease or ulcerative colitis.

• Thiopurines are associated with an increased risk of infection, myelosuppression, liver toxicity, pancreatitis and malignancy.

• Methotrexate is associated with an increased risk of myelosuppression, pulmonary toxicity, liver toxicity and birth defects.

• Anti-TNF-α agents are associated with an increased risk of infection, autoimmunity, demyelinating disease, congestive heart failure and malignancy.

• Anti-integrin therapy is associated with an increased risk of progressive multifocal leukoencepholopathy.

• Hepatosplenic T-cell lymphoma is associated with thiopurine monotherapy as well as thiopurine therapy in combination with anti-TNF-α therapy.

• Physicians have a responsibility to discuss risks with patients in a manner that is understandable and allows them to appreciate the benefits as well as risks associated with therapy. Physicians should also ensure that patients understand which complications of disease are likely to occur if IBD is inadequately treated.

• Patients may be more risk-tolerant than physicians, particularly in situations where clinical remission may be achieved.

• The decision to initiate, continue or cease therapy should be individualized and based on the severity of disease, likelihood of disease progression in the future and the risk associated with the available therapeutic options.