What is the next best step in managing a 45-year-old gentleman with chronic bloody diarrhea, abdominal pain, fecal incontinence, and significant weight loss, diagnosed with severe colonic inflammation and stricture, unresponsive to corticosteroids, mesalamine (Mesalamine), and antibiotics, including Cipro (Ciprofloxacin) and Metronidazole?

From the Guidelines

The recommended approach for this patient is surgical resection of the affected areas of the colon, as the patient has severe colonic inflammation and stricture unresponsive to medical therapy, including corticosteroids, mesalamine, and antibiotics, and this approach is supported by the most recent guidelines for the management of inflammatory bowel disease 1.

Key Considerations

• The patient's symptoms, including chronic bloody diarrhea, abdominal pain, fecal incontinence, and significant weight loss, indicate a severe and debilitating condition that requires prompt and effective treatment.
• The patient's failure to respond to medical therapy, including corticosteroids, mesalamine, and antibiotics, suggests that surgical intervention may be necessary to alleviate symptoms and prevent further complications.
• The presence of a stricture in the colon is a significant concern, as it can lead to bowel obstruction, perforation, and other life-threatening complications if left untreated.

Guideline Recommendations

• The WSES-AAST guidelines for the management of inflammatory bowel disease in the emergency setting recommend surgical intervention for patients with severe colonic inflammation and stricture who are unresponsive to medical therapy 1.
• The British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults also recommend considering surgical intervention for patients with incomplete response to treatment or flare 1.
• The guidelines for the management of inflammatory bowel disease in adults published in 2004 recommend close liaison with a surgeon who specializes in the management of patients with UC and consideration of colectomy for patients who have failed to respond to maximal oral treatment 1.

Conclusion Not Applicable - Next Steps

• The patient should be referred to a surgeon who specializes in the management of inflammatory bowel disease for further evaluation and discussion of surgical options.
• The patient should be closely monitored for any signs of complications, such as bowel obstruction or perforation, and should be prepared for the possibility of emergency surgery if necessary.
• The patient's medical therapy should be optimized and adjusted as needed to manage symptoms and prevent further complications until surgical intervention can be performed.

From the FDA Drug Label

RENFLEXIS is a tumor necrosis factor (TNF) blocker indicated for: Crohn's Disease: • reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. Ulcerative Colitis: • reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

The next best step in managing the patient is to consider Infliximab (IV), as the patient has severe colonic inflammation and stricture, and has been unresponsive to corticosteroids, mesalamine, and antibiotics.

• The patient's symptoms, such as chronic bloody diarrhea, abdominal pain, fecal incontinence, and significant weight loss, are consistent with moderately to severely active disease.
• The patient's inadequate response to conventional therapy makes them a candidate for TNF blocker therapy, such as infliximab.
• The recommended dose for Crohn's Disease or Ulcerative Colitis is 5 mg/kg at 0,2 and 6 weeks, then every 8 weeks 2.

From the Research

Management of Severe Colonic Inflammation

The patient's condition, characterized by chronic bloody diarrhea, abdominal pain, fecal incontinence, and significant weight loss, with a diagnosis of severe colonic inflammation and stricture unresponsive to corticosteroids, mesalamine, and antibiotics, suggests a need for alternative therapeutic approaches.

Consideration of Infliximab Therapy

• Infliximab, an anti-tumor necrosis factor (TNF) agent, has been shown to be effective in treating moderate to severe inflammatory bowel disease (IBD) with a good safety profile 3, 4.
• The use of infliximab can reduce hospitalization risk and the need for surgery in patients with IBD, as demonstrated by randomized controlled trials and observational studies 5.
• Therapeutic drug monitoring (TDM) can help guide clinical decisions in patients receiving infliximab, particularly in identifying those who may require dose optimization 6.

Precision Dosing and Combination Therapy

• Recent literature suggests that precision dosing of infliximab, using therapeutic drug monitoring and Bayesian forecasting methodology, can help optimize treatment outcomes in IBD patients 6.
• A post hoc analysis of a randomized clinical trial found that subcutaneous infliximab monotherapy and combination therapy with immunosuppressants had comparable pharmacokinetics, efficacy, and immunogenicity outcomes in biologic-naïve IBD patients 7.

Next Steps in Management

Given the patient's unresponsiveness to conventional therapies, consideration of infliximab therapy, potentially with precision dosing and therapeutic drug monitoring, may be a viable next step in managing the patient's severe colonic inflammation and stricture. Consultation with a gastroenterologist or other specialist in IBD management is recommended to determine the best course of treatment.