Johnston, R.L., Lutzky, J., Chodhry, A., & Barkin, J.S. (2009). Cytotoxic T-lymphocyte-associated antigen 4 antibody-induced colitis and its management with infliximab. Digestive Diseases and Sciences, 54, 2538–2540. 

To review the use of corticosteroids and infliximab in the treatment of patients with immune-mediated colitis secondary to anti-CTLA-4 antibody treatment

Five patients in a phase III trial for malignant melanoma treatment who developed diarrhea after receiving anti-CTLA-4 antibody treatment were evaluated. Four patients received tremelimumab, and one received ipilimumab. All five patients presented with acute diarrhea within a median of 35 days (range 10–53) after the last anti-CTLA-4 dose. Diarrhea was defined as loose or watery, nonbloody, and occurring four to eight times daily. Laboratory results were benign, and infection diarrhea was ruled out. Each patient underwent flexible sigmoidoscopy that revealed edema, erythema, ulcerations, and fibrinopurulent exudates. All five patients were treated with high-dose corticosteroids (prednisone 40–60 mg by mouth daily) for one week. Patients with continued, relapsed, or partial response beyond one week of treatment were treated with infliximab 5 mg/kg.

• N = 5   
• AGE = 50–78 years
• MALES: 2, FEMALES: 3
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: Malignant melanoma
• OTHER KEY SAMPLE CHARACTERISTICS: No previous history of unexplained diarrhea or inflammatory bowel disease, acute diarrhea after receiving anti-CTLA-4

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Miami, FL

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care 

Prospective, observational trial

Case series report

Treatment with infliximab resulted in a resolution of symptoms within two to three days in all patients. Resolution was defined as a return to baseline bowel habits of one to two solid bowel movements per day. One patient had recurrence of symptoms within three weeks and was given a second treatment with infliximab with success. All patients had a four- to six-week follow-up to ensure resolution. None had a repeat sigmoidoscopy. The authors concluded that, to their knowledge, no untoward side effects to inflixamab have occurred, including infection. The discussion refers to this regimen as based on one article (Beck et al.). The discussion also raises concerning issues about the affect of infliximab on tumor response. The current authors further state that the drug could affect other immune suppressant properties, predisposing patients to serious infection and cancer progression.

Infliximab was effective in resolving immunotherapy-related diarrhea in this small group of patients.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Selective outcomes reporting
• Measurement/methods not well described
• Findings not generalizable

Anti-CTLA-4 antibody treatment can cause immune-mediated colitis. Nurses must be knowledgeable about advances in the treatment of immune-related adverse reactions, such as colitis.