Algorithm for management of refractory Crohn disease in children

6-MP: 6-mercaptopurine; AZA: azathioprine; MTX: methotrexate; anti-TNF: anti-tumor necrosis factor; PCDAI: pediatric ulcerative colitis activity index; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; MRE: magnetic resonance enterography; IV: intravenous.
* Early use of an anti-TNF antibody is an option for selected patients with moderate to severe disease, especially those with risk factors for complicated disease; risk factors include severe perianal disease, steroid unresponsiveness, deep colonic fissuring, extensive disease involving the mid-small bowel, or severe growth failure in late puberty.
¶ Surgical resection also may be appropriate in some patients with growth failure and whose disease is limited to a discrete area of the intestine.
Δ The choice between infliximab and adalimumab typically depends on clinician and patient preferences, such as a preference for subcutaneous administration (adalimumab) versus infusions (infliximab).
◊ Expert opinion varies about how long to continue combination therapy after starting infliximab or adalimumab. Infliximab with low-dose MTX is increasingly used for combination therapy, primarily due to concerns about malignancy risk with 6-MP/AZA. Some clinicians elect to use anti-TNF monotherapy with careful monitoring of therapeutic drug levels instead of combination treatment. For a discussion of the relative risks and benefits, refer to the text of the topic on management of Crohn disease in children and adolescents.
§ Severe adverse effects that warrant discontinuation of infliximab or adalimumab include a severe infusion reaction, refractory psoriasis, drug-induced lupus, or serum sickness. In case a drug is stopped because of an opportunistic infection, it is reasonable to consider resuming the original drug once the infection is cleared.
¥ A good response is suggested by improvement in clinical symptoms within 4 to 8 weeks or a sustained decrease in PCDAI score by 12.5 or more points, ideally confirmed within 3 to 6 months by objective data (eg, improvements in ESR, CRP, repeat imaging with MRE, or colonoscopy).
‡ Infliximab dosing starts at 5 mg/kg per dose IV. If the response to standard dosing is incomplete, the treatment may be escalated by increasing the dose to 10 mg/kg and/or by increasing the frequency of infusions. Adalimumab treatment is typically escalated by increasing the frequency of administration from once every 2 weeks to once a week. Dose escalation is generally attempted before changing to a different drug, but therapeutic drug monitoring of levels and antibodies is suggested to help determine whether dose escalation or changing medications is warranted. For example, patients who have active disease, low levels of infliximab, and low or no levels of antibodies to infliximab may benefit from dose escalation. In contrast, patients with low infliximab concentrations and high titers of antibodies to infliximab will most likely need a different agent. Refer to UpToDate topic for further information about adjustment of the doses and dosing interval.