Meserve, Joseph

ABSTRACTBackground and AimsWe aimed to assess the impact of setons on perianal fistula outcomes in patients with perianal fistulising Crohn's disease (PFCD) treated with anti‐TNF therapy.MethodsWe included patients treated with their first anti‐TNF therapy for PFCD after undergoing a pelvic MRI between 2005 and 2022 from 6 North American centres. Our exposure was one or more setons at the time of anti‐TNF therapy. Our primary outcome was major adverse fistula outcome (MAFO), a composite of repeat local surgical intervention, hospitalisation, or faecal diversion for PFCD, and our secondary outcome was fistula remission defined clinically. We used 1:1 cardinality matching and propensity score weighting to control for fistula severity based on centrally read MRIs, luminal characteristics, and concomitant therapies.ResultsOur analysis included 221 patients: 81 with setons and 140 without setons. After cardinality matching, our cohorts were balanced (standardised difference < 0.1 for all covariates). Patients with setons had similar rates of MAFO (HR 1.23; 95% CI, 0.68–2.21) and fistula remission at 6 months (OR, 0.81; 95% CI, 0.41–1.59) and 12 months (OR, 0.63; 95% CI, 0.31–1.27) compared to patients without setons. Our results remained stable when analysed by propensity score weighting and in a sensitivity analysis of patients who underwent an exam under anaesthesia. In patients with abscesses, there were lower rates of MAFO (HR, 0.49; 95% CI, 0.19–1.25) but not statistically significant in patients with setons.ConclusionsIn this multicentre, setons were not associated with improved fistula outcomes. Future prospective controlled studies are warranted.

Abstract Background Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. Methods We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. Results A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. Conclusion Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.

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.