Loftus, Edward V.

Background: Vedolizumab (VDZ) is a gut-specific α4-β7 integrin antagonist that has demonstrated efficacy in Crohn’s disease (CD) and ulcerative colitis (UC). The safety of VDZ in the perioperative period remains unclear. The aim of this study was to evaluate postoperative complications and perioperative safety in VDZ-treated patients undergoing nonintestinal operations. Methods: A case-matched study was performed at two inflammatory bowel disease (IBD) referral centers. Adult patients with CD and UC who underwent a nonintestinal surgical procedure during treatment with VDZ were included. Patients who had their last VDZ infusion up to 12 weeks before the procedure were considered exposed and were matched in a 1:1 ratio to patients without VDZ therapy, according to type of surgical procedure, age, and sex. The primary outcome was overall risk of early postoperative infectious complications (up to 30 days after surgery), readmissions, reoperations, surgical site infections, and other infections. The VDZ and control groups were subsequently compared using the Pearson χ2 test and Wilcoxon rank sum. Results: We identified 34 patients treated with VDZ who underwent 36 nonintestinal surgical procedures. These patients were matched with 36 control procedures. Postoperative complications were not different between the VDZ-treated and control cohorts for all outcomes analyzed: infectious complications occurred in 14% versus 8% ( p = 0.45), superficial surgical site infections 6% versus 0% ( p = 0.15), reoperations 6% versus 3% ( p = 0.56) and readmissions 11% versus 6% ( p = 0.37). Conclusions: VDZ-treated patients with IBD undergoing nonintestinal procedures did not have an increased risk of overall postoperative infections or other complications compared with matched controls.

SummaryBackgroundPrimary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure.AimTo evaluate the effect of biological therapies on PSC progression in IBD patients.MethodsWe performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017. Hepatic biochemistries were compared using the paired t‐test (patients served as their own controls) ≤3 months before and 6‐8 and 12‐14 months after biological initiation. Radiographic information of biliary stenosis and liver fibrosis were obtained via abdominal ultrasound, abdominal magnetic resonance imaging and magnetic resonance elastography.ResultsUse of adalimumab was associated with a significant decrease in alkaline phosphatase (ALP) after 6‐8 months (P = 0.03; mean change −70 U/L, standard deviation [SD] 88 U/L) compared to vedolizumab (mean change +50 U/L, SD 142 U/L) or infliximab (mean change +37 U/L, SD 183 U/L) but the change was not significant after 12‐14 months (P = 0.24). No significant decreases were observed with AST, ALT, total or direct bilirubin, elastography score or radiographic imaging of biliary tree dilation/strictures with any biological therapy after 6‐8 or 12‐14 months.ConclusionsCurrent evidence suggests that biological therapies used for the treatment of IBD are not effective treatments for PSC. Further study is needed to elucidate any potential beneficial effect of adalimumab on PSC.

Abstract Background We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR. Methods Retrospective review (May 2014–December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan-Meier estimates were used to determine rates of LOR to VDZ . Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (>50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified. Results Cumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohn’s disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25–2.97] in all patients. For Crohn’s disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01–1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients. Conclusions LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening.