Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

Abstract

The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs. New and emerging treatments such as anti-attractants, anti-interleukins, and Janus kinase (JAK) inhibitors will also be discussed.

Anti-TNF Therapy in Crohn’s Disease

“…Anti-TNF treatment currently represents a central treatment modality in Crohn’s disease and can be improved by rapid dose escalation and the use of combination therapy [102]. However, two decades on from their introduction, questions still remain about their use including timing, dosing, monitoring and issues surrounding loss of response such as risk factors, biomarkers, mechanism and strategies for prevention and treatment [79]. These will undoubtedly form the basis of research in the future.…”

“…There is, however, contrasting data from an Irish cohort [74,77] that compared two groups of patients treated with infliximab originator or biosimilars, showing an increased surgery rate, less steroid-free remission rates, and less normalization of inflammatory marker CRP. Further appropriately designed observational studies and efficient pharmacovigilance programmes that improve biosimilars’ safety profile are warranted [79] to address implications of these new drugs and whether existing techniques of drug monitoring, efficacy and safety application. Furthermore, head-to-head trials to assess best treatment pathways [26], as well as close cooperation of regulatory authorities, scientific societies and the pharmaceutical industry would serve to improve knowledge and clinical practice guidelines to standardize the use of biosimilars [76,80].…”

“…Up to 30% of patients do not respond to anti-TNF therapy (primary non-responders) and almost half of the patients who experience a benefit with these drugs will lose clinical benefits within the first year, requiring dose escalation or therapy change [55,81,82], termed “secondary loss of response”. Several studies have demonstrated benefits in empiric switching to a different anti-TNF agent following loss of response; however, short-term remission rates were modest [79,83,84]. …”

“…Analysis of patients from the ACCENT 1 study also demonstrated that those who failed to respond to therapy had lower serum infliximab concentration than those with a sustained response [46]. Early therapeutic drug monitoring (TDM) could be used to prevent loss of response rather than to reverse it (although further research is required to corroborate this [79]), as well as to optimize treatment with anti-TNF antibodies based on actual exposure to the drug rather than according to a standard dosing regimen. …”

“…Long-term therapeutic use of anti-TNF carries with it safety issues which include potential for development of skin lesions, immune reactions, peri-operative complications, infections, cancers and decreased fertility/adverse effects on pregnancy [79,110]. …”