Edward V. Loftus Jr, MD, Editor

Drs Ming-Hsi Wang and Michael Picco of Mayo Clinic Florida review what is known about the most common genetic polymorphisms associated with Crohn’s disease, including NOD2, IL-23, and ATG16L1, and what implications these have on the risk, phenotype, and prognosis of this illness. Drs Satimai Aniwan, Sang Hyoung Park, and I of Mayo Clinic Rochester provide an update on the epidemiology and natural history of Crohn’s disease. Clinical and demographic features that are associated with more adverse outcomes are highlighted so that the clinician can target the level of therapy based on perceived risk. Drs Sahil Khanna and Laura Raffals of Mayo Clinic Rochester describe the complex changes in the intestinal microbiome in patients with Crohn’s disease and discuss how this may be addressed with interventions such as prebiotics, probiotics, and fecal microbial transplantation.

Drs Badr Al-Bawardy and his gastroenterologic and radiologic colleagues from Mayo Clinic Rochester review the various endoscopic and radiologic means by which we assess the severity of inflammation and complications in Crohn’s disease, including endoscopic and radiographic scoring systems.

Crohn’s disease can cause complications. Dr Sushil Garg from the University of Minnesota, Dr Fernando Velayos of Kaiser Permanente Northern California, and Dr John Kisiel of Mayo Clinic Rochester provide an update on cancer risks, both intestinal and nonintestinal, in Crohn’s disease patients, and how this relates to chronic intestinal inflammation as well as various medical therapies. Dr Jill Gaidos of Virginia Commonwealth University and Dr Sunanda Kane from Mayo Clinic Rochester review the impact that Crohn’s disease has upon sexuality and fertility in both men and women and the impact of both disease activity and medications on pregnancy outcomes. Drs Amy Lightner, William Faubion, and J.G. Fletcher of Mayo Clinic Rochester describe the complexity of perianal Crohn’s disease and highlight how an interdisciplinary approach (GI, radiology, surgery) can improve outcomes.

One of the particularly frustrating challenges of Crohn’s disease is its tendency to recur after bowel resection. Dr Siddharth Singh of University of California–San Diego and Dr Geoff Nguyen of Mount Sinai Hospital (Toronto) review the evidence for efficacy of medications in the postoperative setting for preventing or at least decreasing the risk of recurrence and provide a management strategy for (it is hoped) earlier detection of endoscopic recurrence.

Drs Guilherme Piovezani Ramos, Faubion, and Konstantinos Papadakis of Mayo Clinic Rochester review immunologic alterations in Crohn’s disease and highlight which receptors or molecules have been targeted in drug development. Dr Raina Shivashankar from the University of Pennsylvania and Dr Darrell Pardi of Mayo Clinic Rochester provide a succinct review of the evidence of efficacy and safety of anti-TNF agents and anti-integrins in Crohn’s disease and compare and contrast the two drug classes. Dr Parakkal Deepak of Washington University in Saint Louis and Dr William Sandborn of University of California–San Diego review the evidence for efficacy and safety of ustekinumab in Crohn’s disease and highlight an upcoming class of drugs, the anti-IL-23 agents (brazikumab and risankizumab), currently in development. Dr Brigid Boland of University of California–San Diego and Prof Severine Vermeire of University Hospitals Leuven provide an update on various oral small molecules such as the selective Janus kinase 1 inhibitors (eg, filgotinib and upadacitinib), Smad 7 inhibitors (eg, mongersen), and sphingosine-1 phosphate 1 receptor modulators (eg, ozanimod).

The protein-based biologic agents are “tricky” drugs to use due to their immunogenicity and extreme variation in pharmacokinetics. Drs Valerie Heron and Waqqas Afif of McGill University Health Center review the recent literature on the utility of therapeutic drug monitoring of biologics in Crohn’s disease. In the final article, Drs Reena Khanna, Vipul Jairath, and Brian Feagan of the University of Western Ontario emphasize that it is neither disease assessment nor therapies alone that will alter the natural history of Crohn’s disease, but the combination of these two in a “treat to target” approach may get us there.

It is gratifying to look back and see the advances in assessment and management of Crohn’s disease over the past 25 years, but we need to press forward, build upon these gains, and continue to work toward a goal of abolition of intestinal complications and ultimately cure of this enigmatic condition.