Marjolijn Duijvestein1,2,3, Robert Battat1,2, Niels Vande Casteele1,2, Geert R D'Haens3,4, William J Sandborn2, Reena Khanna5,6, Vipul Jairath7,8, Brian G Feagan5,6,9. 1. Robarts Clinical Trials, San Diego, CA, USA. 2. Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. 3. Academic Medical Center, Amsterdam, Netherlands. 4. Robarts Clinical Trials, Amsterdam, Netherlands. 5. Robarts Clinical Trials, London, Canada. 6. Department of Medicine, University of Western Ontario, London, ON, Canada. 7. Robarts Clinical Trials, London, Canada. vipul.jairath@robartsinc.com. 8. Department of Medicine, University of Western Ontario, London, ON, Canada. vipul.jairath@robartsinc.com. 9. Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada.
Abstract
PURPOSE OF REVIEW: This article reviews current treatment options and strategies and provides an update on the status of drug development programs of new therapeutic agents for inflammatory bowel diseases (IBD). RECENT FINDINGS: In the past two decades, tumor necrosis factor antagonist therapy has given clinicians better treatment options. However, not all patients respond to induction therapy with these agents, and of those initially responding, up to 40% ultimately lose response due to suboptimal drug exposure (e.g., caused by immunogenicity), side effects, or other poorly characterized mechanisms. Recently, additional therapies, such as vedolizumab, an integrin blocker that prevents T cell trafficking to the gut, and ustekinumab, an antibody blocking the common p40 subunit of interleukin (IL)-12 and 23, were introduced to the market. In addition, other agents including novel anti-trafficking therapies (e.g., anti-β7 and sphingosine-1-phosphate receptor modulators), antibodies against p19 (unique to IL-23), and small molecules including Janus kinase inhibitors are under investigation in phase II and III trials. Furthermore, the management of IBD has evolved from targeting control of symptoms to suppression of mucosal inflammation. This shift in thinking has been accompanied by the early use of highly effective therapy in poor prognosis patients, accelerated treatment escalation and utilization of a treat to target paradigm approach, and adoption of therapeutic drug monitoring. The treatment landscape for IBD is rapidly evolving with the recent approval of novel biologics as well as several other agents in late phase of clinical development. Moreover, we have started to use agents more intelligently with a focus on risk stratification and early use of highly effective therapy in high-risk patients, treat to target using patient-reported outcomes (PROs), biomarkers, endoscopy, and therapeutic drug monitoring.
PURPOSE OF REVIEW: This article reviews current treatment options and strategies and provides an update on the status of drug development programs of new therapeutic agents for inflammatory bowel diseases (IBD). RECENT FINDINGS: In the past two decades, tumor necrosis factor antagonist therapy has given clinicians better treatment options. However, not all patients respond to induction therapy with these agents, and of those initially responding, up to 40% ultimately lose response due to suboptimal drug exposure (e.g., caused by immunogenicity), side effects, or other poorly characterized mechanisms. Recently, additional therapies, such as vedolizumab, an integrin blocker that prevents T cell trafficking to the gut, and ustekinumab, an antibody blocking the common p40 subunit of interleukin (IL)-12 and 23, were introduced to the market. In addition, other agents including novel anti-trafficking therapies (e.g., anti-β7 and sphingosine-1-phosphate receptor modulators), antibodies against p19 (unique to IL-23), and small molecules including Janus kinase inhibitors are under investigation in phase II and III trials. Furthermore, the management of IBD has evolved from targeting control of symptoms to suppression of mucosal inflammation. This shift in thinking has been accompanied by the early use of highly effective therapy in poor prognosis patients, accelerated treatment escalation and utilization of a treat to target paradigm approach, and adoption of therapeutic drug monitoring. The treatment landscape for IBD is rapidly evolving with the recent approval of novel biologics as well as several other agents in late phase of clinical development. Moreover, we have started to use agents more intelligently with a focus on risk stratification and early use of highly effective therapy in high-risk patients, treat to target using patient-reported outcomes (PROs), biomarkers, endoscopy, and therapeutic drug monitoring.
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