Review article: managing the adverse events caused by anti‐TNF therapy in inflammatory bowel disease

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 includedwere "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.

Identification of a Distal Locus Enhancer Element That Controls Cell Type–Specific TNF and LTA Gene Expression in Human T Cells

“…Currently, several Food and Drug Administration-approved biological inhibitors that broadly inhibit TNF activity across all cell types are in clinical use for the treatment of diverse autoimmune disorders (59). Although of great clinical value, these agents are also complicated by serious adverse events in some patients because of their broad mode of action (60,61). The ability to selectively inhibit TNFR signaling by inhibiting TNF in a celland/or inducer-specific manner, and to inhibit LT-a expression in T cells that are relevant to specific disease pathologies would be a major advance.…”

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

“…The most significant breakthrough thus far in treating IBD, and is perhaps the classic example of suppressing a pro-inflammatory cytokine, is anti-TNF treatment. However, neutralizing TNF by no means helps all patients, as 30% of patients do not respond 1 year after treatment (332). Moreover, most of strategies targeting single effector cytokines in IBD have been disappointing in clinical trials (333), reinforcing the complexity and heterogeneity of IBD.…”

Management of the Elderly Inflammatory Bowel Disease Patient

“…The most prominent adverse events due to anti TNFα therapy include infusion reactions, abdominal discomfort, infections (including bacterial, viral, fungal, and opportunistic infections) as well as rare occurrence of autoimmune, dermatological disorders, cardiac, and neurological conditions [75]. Cottone et al [73] reported a 12% risk of serious infection in the elderly on anti-TNF agents, including pneumonia and sepsis.…”