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INTRODUCTION: Previous studies have shown that ustekinumab (UST) is an effective induction and maintenance therapy for patients with moderate to severe Crohn's Disease (CD). We sought to examine the real-world efficacy and safety of UST and whether UST dose escalation helps to recapture clinical response. METHODS: All patients who received the initial weight-based UST infusion between 4/2017 and 4/2018 were identified through a query of the EMR. Patients were followed from the time they initiated UST through 5/2019 or their date of UST discontinuation, whichever came first. Specifically, patients who lost response to UST 90 mg injection every 8 wk dosing and were then dose escalated to either every 4 or 6 wk dosing were identified. Recaptured clinical response to dose escalation was determined by reviewing clinical documentation and assessing for a reduction of ≥3 in the modified Harvey Bradshaw index (mHBI) after ≥8 wks following dose escalation. RESULTS: We included 27 patients with CD [median age 40 (range 24-61); 56% male; 96% tumor necrosis factor (TNF)-antagonist exposed]. Table 1 compares characteristics and outcomes of patients who underwent dose escalation vs. those who remained on regular dosing. Of the 11 dose escalated patients, 9 were switched to an every 4 wk regimen while the other 2 were switched to an every 6 wk regimen. Patients who underwent dose escalation were more likely to be a smoker (18% vs. 13%), have a history of perianal disease (73% vs. 38%), have previously tried a greater number of biologics (2.7 vs. 1.9), and be exposed to concomitant steroid (55% vs. 25%). Moreover, patients who underwent dose escalation were less likely to achieve steroid discontinuation within the first 8 wks compared to those who remained on regular dosing (9% vs. 50%). The only adverse event in the dose escalation group was one case of pneumonia. Table 2 further examines those patients that underwent dose escalation. The median mHBI improved from 9 to 7 following dose escalation. Recaptured clinical response occurred at a rate of 6/11 (55%) based on clinical documentation and 3/11 (27%) based on mHBI. CONCLUSION: UST dose escalation from 90 mg every 8 wks to either every 4 or 6 wk dosing allowed for recaptured clinical response in ∼25-50% of CD patients. There were minimal adverse events in patients who were dose escalated. Given its safety profile, dose escalation should be considered in patients with moderate to severe CD who have incomplete response to UST.

INTRODUCTION: Clostridium difficile enteritis (CDE) is rare, but is increasingly diagnosed among those who have undergone colectomy. After colectomy, colonic-type bacterial flora including Clostridium difficile are able to colonize, and under the right circumstances, infect the small bowel. The reported mortality of CDE is high, likely due in part to the emergence of a virulent strain of Clostridium difficile, NAP1/BI/027. Physicians should have a high index of suspicion for CDE, particularly among patients with antibiotic exposure after colectomy. CASE DESCRIPTION/METHODS: A 50-year-old-woman with a previous history of Clostridium difficile infection (CDI) and colonic inertia status post total abdominal colectomy with ileorectal anastomosis three months prior presented with waves of left lower quadrant abdominal pain, abdominal distention, nausea, and vomiting. In the three weeks prior to admission, she completed courses of Amoxicillin and Trimethoprim-sulfamethoxazole for UTI. CT abdomen/pelvis with contrast showed 20 cm of circumferential thickening of the distal small bowel with associated free fluid and mesenteric inflammation proximal to unaffected ileorectal anastomosis. Laboratory evaluation was notable only for mild leukocytosis (12,000 cells/µL) with no bands. On admission, the patient had a nasogastric (NG) tube placed for abdominal decompression. A Bisacodyl suppository was prescribed, and the patient had a bowel movement that resulted positive for Clostridium difficile toxin DNA PCR. The patient was diagnosed with CDE. She was initially started on NG Vancomycin 150 mg every 6 hours for a first recurrence of CDI, which was then escalated to 500 mg every 6 hours with the addition of IV Metronidazole. This resulted in resolution of symptoms and ileus. DISCUSSION: Our patient had several CDE risk factors including a prior history of colectomy and recent antibiotic exposure. In addition to CDE risk factors, our patient also had two CDI risk factors - chronic acid suppression and previous history of CDI. Additional research is needed to determine if other typical CDI risk factors also play a role in the development of CDE. In patients with altered gastrointestinal anatomy or obstruction, it may be challenging to confirm the diagnosis using stool-based PCR toxin studies. Abdominal CT scan may be helpful in making the diagnosis. Much like our patient, previous studies have demonstrated circumferential edema and mesenteric stranding of the small bowel as common radiologic features of CDE.

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