What is the next step in managing stricturing Crohn's disease with antibodies to infliximab (Infliximab is a brand name, generic name is Chimeric monoclonal antibody against Tumor Necrosis Factor-alpha, TNF-alpha)?

From the Guidelines

For stricturing Crohn's disease with infliximab antibodies, the next step should be switching to a different biologic agent, preferably one from a different class, such as ustekinumab (Stelara) with an initial IV infusion based on weight, followed by 90 mg subcutaneous injections every 8 weeks, as recommended by the most recent guidelines 1. This approach is supported by the AGA clinical practice guidelines on the medical management of moderate to severe luminal and perianal fistulizing Crohn's disease, which suggests the use of ustekinumab over no treatment for the induction and maintenance of remission in adult outpatients with moderate to severe CD 1. The development of antibodies to infliximab indicates immunogenicity, which reduces drug efficacy and increases risk of infusion reactions, as noted in the british society of gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults 1. Measuring drug levels and antibodies can confirm this situation, and the patient should be evaluated for stricture severity with imaging and possibly endoscopy to determine if endoscopic balloon dilation or surgical intervention is needed for the stricturing component, as biologics alone may not resolve established fibrotic strictures. Additionally, nutritional support and anti-inflammatory diet modifications should also be implemented to reduce symptoms while transitioning therapies. Key considerations in this decision include the patient's previous response to anti-TNF therapy, the presence of high-titre antibodies, and the potential benefits and risks of switching to a different biologic agent, as discussed in the ECCO guidelines on therapeutics in Crohn's disease: medical treatment 1. The most recent and highest quality study, the AGA clinical practice guidelines 1, provides the strongest evidence for this recommendation, and should be prioritized in guiding clinical decision-making. Some studies suggest that combination therapy with an immunomodulator may reduce immunogenicity and improve treatment outcomes, but the evidence for this approach is not as strong as the evidence for switching to a different biologic agent 1. Overall, the best course of action is to switch to a different biologic agent, such as ustekinumab, and to consider combination therapy with an immunomodulator on a case-by-case basis.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Managing Stricture in Crohn's Disease

The management of stricturing Crohn's disease, especially in patients who have developed antibodies to infliximab, involves several strategies.

• The use of alternative anti-TNF agents such as adalimumab or certolizumab pegol may be considered, as these drugs have shown efficacy in patients who have lost response to infliximab 2, 3, 4, 5.
• Adalimumab, in particular, has been shown to be effective in inducing and maintaining remission in Crohn's disease, with a similar efficacy profile to infliximab 5.
• Endoscopic balloon dilation is also an effective strategy for managing strictures, particularly for de novo and anastomotic strictures ≤ 5 cm in length 6.
• The combination of anti-TNF drug therapy and endoscopic balloon dilation may provide greater benefit than individual therapies, although further evaluation is needed 6.

Treatment Options

Treatment options for stricturing Crohn's disease include:

• Anti-TNF therapy, such as infliximab, adalimumab, or certolizumab pegol, which can help reduce inflammation and prevent stricture formation 2, 3, 4, 5.
• Endoscopic therapy, including balloon dilation, needle knife stricturotomy, and stent insertion, which can help relieve obstruction and improve symptoms 6.
• Optimization of current drug and endoscopic therapy, as well as the incorporation of newer therapies, is needed to improve outcomes for patients with stricturing Crohn's disease 6.

Considerations

When considering treatment options for stricturing Crohn's disease, several factors should be taken into account, including:

• The presence of antibodies to infliximab, which may impact the efficacy of anti-TNF therapy 2, 4.
• The length and location of the stricture, which may influence the choice of endoscopic therapy 6.
• The patient's overall health status and medical history, which may impact the risk of adverse events associated with treatment 3, 5.