Management of moderate to severe ileocolonic Crohn disease in children and adolescents

6-MP: 6-mercaptopurine; AZA: azathioprine; CD: Crohn disease; CRP: C-reactive protein; EEN: exclusive enteral nutrition; ESR: erythrocyte sedimentation rate; IV: intravenous; MTX: methotrexate; PEN: partial enteral nutrition; TNF: tumor necrosis factor.

* Preliminary studies suggest that PEN with a specific exclusion diet may be as effective and better accepted by patients compared with EEN^[4].

¶ For more severe disease, glucocorticoids are typically started IV, then transitioned to oral if the patient responds well. For patients with isolated rectal CD, glucocorticoid enemas/suppositories may be used in conjunction with EEN. In patients with severe disease, glucocorticoids may be used in combination with EEN to achieve a more rapid response.

Δ Many clinicians prefer to avoid thiopurines (6-MP/AZA) because of the slight increase in absolute risk for lymphoma and nonmelanoma skin cancers. The debate continues on the benefit-to-risk ratio of thiopurines. MTX or early use of anti-TNF therapies are increasingly being utilized as alternatives.

◊ Aminosalicylates (eg, mesalamine, sulfasalazine) are attractive because of low toxicity, but it is unclear if these drugs are superior to placebo in preventing relapse. As a result, immunomodulators (6-MP/AZA or MTX) or anti-TNF antibodies are generally used for maintenance therapy for patients with moderate or severe disease.

§ Dietary therapies that are sometimes used for maintenance in CD with variable success include partial enteral nutrition or CD exclusion diet.

¥ Anti-TNF medications include infliximab, adalimumab, and biosimilars. For optimal effect, anti-TNF drug dosing should be adjusted using therapeutic drug monitoring.

‡ Relapse may include clinical symptoms of Crohn disease or other evidence of persistent disease activity including laboratory evidence of persistent inflammation (elevated ESR or CRP) or findings from endoscopy or imaging. Very mild relapses could be managed by escalating the maintenance regimen rather than reinduction.

† In general, patients requiring more than 1 course of glucocorticoids within 1 year should be advanced to an anti-TNF medication or different immunomodulator.

** Expert opinion varies about combination therapy with a biologic agent and an immunomodulator. Combination therapy reduces the risk of antibody formation (which can cause loss of response to the biologic agent) and improves remission rates. However, combination therapy (especially with 6-MP or AZA) is also associated with a small risk of lymphoma. For a discussion of the relative risks and benefits, refer to UpToDate topic text on medical therapies for CD in children and adolescents.^[5]