Ustekinumab is effective in biological refractory Crohn's disease patients–regardless of approval study selection criteria

BACKGROUND/AIMS: Ustekinumab is effective in active Crohn's disease. In a retrospective study, we assessed the clinical outcome in nonresponders to anti-tumor necrosis factor therapy, and/or conventional therapy and/or the α4β7-integrin inhibitor vedolizumab. As approval study populations do not always reflect the average “real world” patient cohort, we assessed weather patients who would not have qualified for approval studies show similar outcomes. METHODS: Forty-one patients with mild to severe active Crohn's disease were treated with ustekinumab (intravenous 6 mg per kg/body weight) followed by subcutaneous ustekinumab (90 mg) at week 8. Depending on the clinical response maintenance therapy was chosen every 8 or 12 weeks. Clinical response was defined by Crohn's Disease Activity Index (CDAI) decline, decline of stool frequency or clinical improvement. Inclusion criteria for approval studies were assessed. RESULTS: The 58.5% (24/41) showed clinical response to ustekinumab. The 58.3% of this group (14/24) achieved clinical remission. Clinical response correlated significantly with drop of stool frequency and improvement of CDAI score. The 39 out of 41 patients had no side effects and we observed no serious infections. About a third of our patients would not have met ustekinumab approval study criteria. However, patients who did not meet study criteria showed clinical improvement numerically in the same range compared to patients who would have qualified for approval studies. CONCLUSIONS: Ustekinumab is effective, safe and well tolerated in a highly therapy refractory patient cohort. Even though a reasonable number of patients did not meet ustekinumab approval study criteria, approval study results seem to be representative to the overall patient cohort.

Endoscopic Balloon Dilation for Crohn’s Disease-Associated Strictures

Management of intestinal strictures associated with Crohn's disease (CD) is clinically challenging despite advanced medical therapy directed toward mucosal healing to positively influence the natural course of CD-associated complications. Although medical therapy is available for inflammatory strictures, therapy of fibrostenotic strictures is the domain of surgery and endoscopy. Endoscopic balloon dilation (EBD) has been recognized as a well-established first-line procedure in terms of safety and efficacy. Although surgery is a valuable treatment modality for the management of CD-related strictures, EBD can help prevent multiple surgical interventions, which might in the long-term lead to a risk of short bowel syndrome. In this review we discuss requirements, techniques, safety, short- and long-term outcomes, as well as combinations of this procedure with surgical and medical treatment in CD-associated intestinal strictures.