Overall and comparative safety of biologic and immunosuppressive therapy in inflammatory bowel diseases

ABSTRACT

Introduction: Efficacy and safety are key aspects when choosing therapies for patients with inflammatory bowel diseases (IBD). While several randomized trials and indirect comparisons have informed the comparative efficacy of medications, there has been a limited synthesis of safety of different agents.

Areas covered: We focus on the overall and comparative risk of serious and opportunistic infections and malignancy of biologic and immunosuppressive therapy in IBD, based on randomized trials, open-label extension and registry studies, and real-world comparative observational studies.

Expert opinion: TNFα antagonists may be more immunosuppressive than non-TNF-targeted biologic agents and increase the risk of systemic infections. Most consistent risk factors for serious infections include use of combination therapy with immunosuppressive agents and/or corticosteroids, moderate to severe disease activity, and older age. TNFα antagonists may also be associated with an increased risk of lymphoma, especially when combined with thiopurines. Real-world comparative safety studies, especially with newer biologic agents, are warranted to inform decision-making. Comparative safety of pharmacotherapy for IBD should be viewed in conjunction with efficacy and in the context of treatment strategies/approach, rather than in the context of specific agents used.

KEYWORDS:

• Cancer
• infection
• lymphoma
• immunosuppression
• ulcerative colitis
• Crohn’s disease

Article Highlights

• Currently approved biologic medications including TNFα antagonists, vedolizumab, ustekinumab, as well as targeted small molecules like tofacitinib may be associated with an increased risk of serious infections. Risk of serious infections may be higher with TNFα antagonists than others, especially gut-selective vedolizumab.

• Most consistent risk factors for serious infections include the use of combination therapy with immunosuppressive agents and/or corticosteroids, moderate to severe disease activity, and older age.

• TNFα antagonists may also be associated with an increased risk of lymphoma, particularly when used in combination with thiopurines. There are limited data on the risk of malignancy with newer non-TNF-targeting biologics including vedolizumab and ustekinumab or targeted small molecules such as tofacitinib, in patients with IBD.

• Comparative safety of pharmacotherapy for IBD should be viewed in conjunction with efficacy and in the context of treatment strategies/approach, rather than in the context of specific agents used.

• Well-designed comparative real-world studies are warranted to optimally inform risks associated with newer non-TNF-targeting biologics, especially over longer-term horizons which are not captured within the confines of clinical trials.

• This box summarizes key points contained in the article

Declaration of interest

S Singh has been supported by the NIDDK K23DK117058, the American College of Gastroenterology Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award (#404614). Research grant support from AbbVie; Consulting fees from AbbVie, Takeda, AMAG Pharmaceuticals; Honorarium from Pfizer for grant review. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases K23DK117058 to Siddharth Singh. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.