Available online 28 March 2024, 151398

Author links open overlay panelAbstract

Management of inflammatory bowel disease, both Crohn's disease (CD) and ulcerative colitis (UC), has seen a seismic shift over the past decade. Over the past five years, there has been the introduction of many new therapies with differing mechanisms of action and a goal of achieving mucosal healing, as well as clinical and biochemical remission (1,2). In addition, management is aimed at restoring normal growth and normalizing quality of life. The ultimate goal is to individualize medical management and determine the right drug for the right patient by identifying which inflammatory pathway is predominant and avoiding unwarranted lack of efficacy or side effects through biomarkers and risk prognostication. Patient's age, location of disease, behavior (inflammatory vs. penetrating/structuring), severity and growth delay all play into deciding on the best treatment approach. Ultimately, early intervention is key in preventing complications. The therapeutic approaches to management can be broken down to nutritional therapy, biologic agents, immunomodulators (including corticosteroids), aminosalicylates and antibiotics. There are numerous other therapies, such as small molecule agents recently approved in adults, which are garnering a great deal of interest.

Section snippetsEnteral Nutrition

Nutritional therapy can be broken down to exclusive enteral nutrition (EEN), partial enteral nutrition (PEN) or dietary modification. These approaches are utilized and effective in CD, but studies are lacking in UC.

Anti-Tumor Necrosis Factor (Anti-TNF)

Anti-TNF agents target a pro-inflammatory cytokine upregulated in the lamina propria of patients with IBD17. There are various agents within this class, including infliximab, adalimumab, golimumab and certolizumab. They are effective at both inducing and maintaining remission, as well as mucosal healing1, 18, 19, 20, 21. Early utilization during the inflammatory phase of disease is associated with better long-term response22,23. The European Society of Pediatric Gastroenterology, Hepatology and

Corticosteroids

Corticosteroids may be utilized to induce remission rapidly and short term, but one must consider the plethora of adverse effects (infection, abscess, weight gain, cushingoid appearance, osteoporosis, cataracts)63, 64, 65. It should be considered in CD when EEN is not tolerated or ineffective66. It is also effective for moderate-to-severe UC and acute severe colitis67,68. Prednisone and Solumedrol dosing is typically 1-2mg/kg with a max of 40mg/day. This must be tapered once remission is

Aminosalicylates (5-ASA)

These are very effective agents for the induction and maintenance of remission in mild to moderate pediatric UC. ESPGHAN recommends ASAs as first line therapy for mild-moderate UC73. It induces remission in 35-55% of patients with clinical responses noted by week 299,100. There are no pediatric maintenance studies. Distal disease (proctitis) often responds well to rectal therapy, while more extended disease requires an oral preparation. There is evidence in adults that a combination of rectal

Antibiotics

A Cochrane review in adults did not find benefit with antibiotics for induction or maintenance of disease104. Ciprofloxacin or metronidazole may be used as an adjuvant for perianal fistulizing Crohn's disease, showing better outcomes than anti-TNF alone105. The dose of metronidazole is 30 mg/kg/day divided into two to three doses and ciprofloxacin is 20 mg/kg/day divided twice a day.

There is literature supporting their use in acute severe colitis as rescue therapy, but it is limited, thus not

On the Horizon

Pediatric FDA approval typically lags adult approval by 7-10 years109. Recently, there have been agents approved in adults with promising data and adverse effect profiles. These include the small molecule agents, as well as anti-IL23 therapy.

Small molecule agents have low molecular weight (especially compared to biologics), short half-lives, and are administered orally. These agents target different pathways and currently approved therapies include the janus kinase (JAK) inhibitors and

Conclusion

Through significant advances in our understanding of the underlying immune mechanisms involved in the pathophysiology of IBD, the treatment armamentarium has significantly improved. We now have multiple mechanisms of action to target with various modes of administration available. Oral agents being approved in adults and currently under investigation in pediatrics fulfill that unmet need of easier administration. There are reports and studies underway investigating combination therapy with

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