From the Guidelines
The best next step for this 40-year-old woman with severe ulcerative colitis who has failed to respond to IV methylprednisolone is to initiate rescue therapy with infliximab, a TNF-alpha inhibitor, at a dose of 5-10 mg/kg intravenously at weeks 0,2, and 6 for induction, followed by maintenance therapy every 8 weeks. Alternatively, cyclosporine at 2 mg/kg/day as a continuous IV infusion could be considered. The patient's presentation with tachycardia, abdominal tenderness, decreased appetite, anemia, and leukocytosis indicates severe disease activity with systemic involvement. Failure to respond to IV corticosteroids after 3-5 days is considered steroid-refractory disease, which carries a high risk of complications including toxic megacolon and perforation, as noted in the study by De Simone et al. 1. Infliximab works by blocking tumor necrosis factor-alpha, a key inflammatory cytokine in ulcerative colitis, while cyclosporine inhibits T-cell activation. These medications can induce remission in approximately 60-70% of steroid-refractory cases, potentially avoiding emergency colectomy, as supported by the WSES-AAST guidelines 1 and the review article by Alimentary Pharmacology and Therapeutics 1. Close monitoring for infection, particularly opportunistic infections, is essential during treatment due to the immunosuppressive effects of these medications. Surgical consultation should be obtained concurrently for possible colectomy if medical therapy fails, as emphasized in the third European evidence-based consensus on diagnosis and management of ulcerative colitis 1. Key considerations in management include:
- Early assessment and decision-making for rescue therapy or surgery
- Use of infliximab or cyclosporine as rescue therapy for steroid-refractory disease
- Importance of monitoring for complications and adjusting treatment accordingly
- Role of surgical consultation in cases where medical therapy is unlikely to be effective or has failed. The most recent and highest quality study, the WSES-AAST guidelines 1, prioritizes a tailored approach to the patient with acute severe colitis, including initial conservative management and early consideration of rescue therapy or surgery. This approach is supported by the other studies, including the review article by Alimentary Pharmacology and Therapeutics 1 and the third European evidence-based consensus on diagnosis and management of ulcerative colitis 1. Overall, the best next step for this patient is to initiate rescue therapy with infliximab or cyclosporine, with concurrent surgical consultation, as supported by the most recent and highest quality evidence 1.
From the FDA Drug Label
The recommended dose of RENFLEXIS is 5 mg/kg given as an intravenous induction regimen at 0,2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adult patients with moderately to severely active ulcerative colitis. In Study UC I, this effect was maintained through Week 54 (21% in infliximab treatment groups vs. 9% in placebo group). The infliximab-associated response was generally similar in the 5 mg/kg and 10 mg/kg dose groups
The best next step for a 40-year-old woman with severe ulcerative colitis who has not improved with intravenous (IV) methylprednisone (corticosteroids) is to initiate infliximab.
- Key points:
- Infliximab has been shown to be effective in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis.
- The recommended dose is 5 mg/kg given as an intravenous induction regimen at 0,2, and 6 weeks, followed by a maintenance regimen of 5 mg/kg every 8 weeks.
- The patient's lack of response to corticosteroids and severe symptoms suggest the need for a more aggressive treatment approach, such as biologic therapy with infliximab 2, 2.
From the Research
Patient Assessment
The patient is a 40-year-old woman with severe ulcerative colitis, presenting with symptoms of bloody diarrhea, crampy abdominal pain, tachycardia, abdominal tenderness, decreased appetite, anemia, and leukocytosis. Despite treatment with intravenous methylprednisone, she has not shown significant improvement.
Treatment Options
Considering the patient's condition and lack of response to corticosteroids, the following options are available:
- Initiate azathioprine: This option may not be the best next step, as the patient has already shown a poor response to intravenous methylprednisone, and azathioprine may take several weeks to become effective 3.
- Initiate broad-spectrum antibiotics: There is no clear indication of an infectious cause for the patient's symptoms, and the Clostridium difficile toxin stool test was negative.
- Initiate infliximab: This option is a viable rescue therapy for patients with steroid-refractory severe ulcerative colitis, as shown in a study where 76% of patients were discharged without colectomy after receiving infliximab 4.
- Consult General surgery for colectomy: This option may be considered if the patient's condition does not improve with further medical treatment, as unresponsiveness to intravenous steroid therapy, anemia, and the need for blood transfusion are major predictors for colectomy 5.
Best Next Step
Based on the available evidence, the best next step for this patient would be to:
- Initiate infliximab, as it has been shown to be effective in inducing and maintaining remission in patients with refractory ulcerative colitis 6, 4. Key points to consider:
- The patient's lack of response to intravenous methylprednisone indicates a need for alternative treatment options.
- Infliximab has been shown to be effective in reducing symptoms and inducing remission in patients with severe ulcerative colitis.
- The patient's anemia, leukocytosis, and abdominal tenderness suggest a severe disease course, which may require more aggressive treatment.