Review Article

Managing the Adverse Events Caused by Anti-TNF Therapy in Inflammatory Bowel Disease

Uday N. Shivaji; Caroline L. Sharratt; Tom Thomas; Samuel C. L. Smith; Marietta Iacucci; Gordon W. Moran; Subrata Ghosh; Neeraj Bhala

Disclosures

Aliment Pharmacol Ther. 2019;49(6):664-680. 

In This Article

Abstract and Introduction

Abstract

Background: Biological therapy is currently widely used to treat IBD. Infliximab, adalimumab and golimumab are currently licensed anti-TNF therapies. Biosimilar anti-TNF monoclonal antibodies are increasingly used. Anti-TNF therapies are widely used and their adverse effects are well characterised, and may cause significant morbidity and mortality in a small proportion of exposed patients. Gastroenterologists need to understand the mechanisms for these effects, recognise these swiftly and manage such events appropriately.

Aim: To cover the range of potential adverse reactions as a result of biologic therapy and specifically management of these events.

Methods: A Medline and Pubmed search was undertaken. Search terms included were "anti-TNF," "infliximab" or "adalimumab" or "golimumab" combined with the keywords "ulcerative colitis" or "Crohn's disease" or "inflammatory bowel disease" and then narrowed to articles containing the keywords "complications," "side effects" or "adverse events" or "safety profile." International guidelines were also reviewed where relevant.

Results: Adverse events discussed in this review include infusion reactions, blood disorders and infections (including bacterial, viral, fungal and opportunistic infections) as well as autoimmune, dermatological disorders, cardiac and neurological conditions. Malignancies including solid organ, haematological and those linked to viral disease are discussed.

Conclusions: Anti-TNF therapy has wide-ranging effects on the immune system resulting in a spectrum of potential adverse events in a small proportion of patients. Research advances are improving the understanding, recognition and management of these adverse events.

Introduction

The use of biologics is currently approved for moderate-to-severe Crohn's disease (CD) and moderate-to-severe ulcerative colitis (UC).[1–9] Infliximab, adalimumab and golimumab are antibodies to tumour necrosis factor-α (TNFα). These drugs work on a common pathway of blocking TNFα, a pro-inflammatory cytokine closely linked to acute phase reaction and systemic inflammation, thereby reducing the degree of damage to tissues. These have been developed using different techniques therefore conferring different degrees of immunogenicity. (Infliximab [human-chimeric], adalimumab [fully human], golimumab [fully human], certolizumab [recombinant pegylated humanised Fab' fragment]).

These medications have transformed medical treatment options for IBD in recent years and are prescribed in increasing numbers. As there are less golimumab exposed patients than the other two anti-TNF monoclonal antibodies, less adverse effects have been reported but generally most adverse effects are class effects. Clinicians need to be aware of and recognise adverse events (AE/AEs) that may result from the use of these drugs and also have clear management strategies in different scenarios. This comprehensive review summarises a range of possible AEs providing evidence based guidance where available and pragmatic guidance for areas where evidence is lacking.

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