Explore the vast range of titles available.

ObjectiveEvaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn’s disease failing conventional therapy.DesignA multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn’s disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty.ResultsIn total, 143 patients were randomised. Mean Crohn’s disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference €−8931; 95% CI €−12 087 to €−5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference €−5729, 95% CI €−10 606 to €172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of €20 000/QALY gained and 0.99 at a WTP of €500/point of improvement in IBDQ Score.ConclusionLaparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab.Clinical trial registration numberDutch Trial Registry NTR1150; EudraCT number 2007-005042-20 (closed on 14 October 2015).

Abstract Background Crohn’s disease is a chronic inflammatory bowel disease that affects the gastrointestinal tract. Common biologic families used to treat Crohn’s are tumor necrosis factor (TNF)-α blockers (infliximab and adalimumab) and immune cell adhesion blockers (vedolizumab). Given their differing mechanisms of action, the ability to monitor response and predict treatment efficacy via easy-to-obtain blood draws remains an unmet need. Methods To investigate these gaps in knowledge, we leveraged 2 prospective cohorts (LOVE-CD, TAILORIX) and profiled their serum using high-dimensional isobaric-labeled proteomics before treatment and 6 weeks after treatment initiation with either vedolizumab or infliximab. Results The proportion of patients endoscopically responding to treatment was comparable among infliximab and vedolizumab cohorts; however, the impact of vedolizumab on patient sera was negligible. In contrast, infliximab treatment induced a robust response including increased blood-gas regulatory response proteins, and concomitant decreases in inflammation-related proteins. Further analysis comparing infliximab responders and nonresponders revealed a lingering innate immune enrichments in nonresponders and a unique protease regulation signature related to clotting cascades in responders. Lastly, using samples prior to infliximab treatment, we highlight serum protein biomarkers that potentially predict a positive response to infliximab treatment. Conclusions These results will positively impact the determination of appropriate patient treatment and inform the selection of clinical trial outcome metrics.

Abstract Background and Aims Point-of-care tests (POCT) enable immediate measurement of anti-TNF blood concentrations. This study examined the association between loss of response (LOR) to infliximab (IFX) or adalimumab (ADL) and serum concentrations measured with POCT and enzyme-linked immunosorbent assay (ELISA) in inflammatory bowel disease (IBD) patients. Methods Patients with IBD with stored IFX or ADL serum samples were recruited. POCT was conducted, agreement with ELISA was evaluated using Bland–Altman plots. The primary endpoint was LOR defined as change in therapy, IBD-related surgery, new actively draining fistula, and/or endoscopic deterioration. ROC curves and quartile analysis assessed the association between concentrations and LOR. Results A total of 176 patients were included (92 IFX/84 ADL, 154 Crohn’s disease, and 22 ulcerative colitis). Median follow-up time was 20 months (interquartile range 9-38). LOR occurred in 37/84 (44%) ADL users and 55/92 (60%) IFX users. Median serum concentrations were significantly lower in LOR patients compared with sustained response, measured by both techniques for ADL (POCT: 6.45 vs 13.48 µg/mL, P <.001; ELISA: 4.80 vs 8.80 µg/mL, P <.001) and IFX (POCT: 2.39 vs 6.50 µg/mL, P <.001; ELISA: 1.70 vs 4.40 µg/mL, P <.001). Quartile analysis revealed that higher serum concentrations were associated with maintained response. ROC curve analysis demonstrated good or excellent discrimination for POCT and ELISA in association with LOR (AUC IFX: POCT = 0.82, ELISA = 0.76; AUC ADL: POCT = 0.82, ELISA = 0.81; all P <.0001). An overestimation of serum concentrations with POCT was observed. Conclusions Serum ADL and IFX POCT concentrations are comparable to ELISA and associated with LOR, indicating its clinical utility. Lay Summary This study assessed the association between loss of response (LOR) and infliximab or adalimumab serum concentrations measured by point-of-care testing and ELISA in inflammatory bowel disease patients. POCT correlated well with LOR, supporting its utility in therapeutic drug monitoring.

Background and Aims Previous literature suggests that faecal calprotectin (FC) discriminates Crohn's disease perianal fistulas from cryptoglandular fistulas, irrespective of luminal disease. This study aims to prospectively validate this and analyse if increased local fistula calprotectin levels are associated with fistula characteristics. Methods In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anaesthesia were included. Faecal and fistula tract scraping calprotectin levels were determined. The primary objective was to analyse whether FC levels could be used to differentiate between Crohn's disease and cryptoglandular perianal fistulas. Secondary outcome parameters were the levels of local calprotectin in fistula scrapings and their correlation with fistula characteristics. Results Sixty‐three patients were included in this study (perianal Crohn's disease; 45, cryptoglandular; 18). Faecal calprotectin levels were significantly higher in Crohn's disease patients compared with cryptoglandular fistula (354.3 [58.8–1076.3] vs. 47.3 [14.6–233.6] μg/g, p = 0.003). Faecal calprotectin could accurately discriminate Crohn's disease patients with active luminal disease from patients without luminal disease (median [interquartile range]) (1167.0 [557.0–2806.3] vs. 93.0 [47.5–571.6] μg/g, p = 0.001). Faecal calprotectin was not related to calprotectin levels in fistula scrapings. No fistula characteristic was found to be correlated to scraping calprotectin, but a correlation was found with the TOpCLASS classification system, which stratifies fistulas according to disease severity and outcome: class 2a (amenable for repair), class 2b (symptom control) and class 2c (gradually debilitating disease): 140[31.0–149.0]) μg/g versus 706[198.5–1936] μg/g versus 4000[1337–5894] μg/g, p < 0.001). Scraping calprotectin was also related to pronounced hyperintensity of the fistula tract on MRI in Crohn's disease patients: (69.0[30.0–821.0] vs. 1284.0[204.3–4185.5]; p = 0.01)) and cryptoglandular patients: (30.0[13.5–80.5] vs. 3012.0 [923.8–5021.0]; p = 0.002). Conclusion Crohn's disease and cryptoglandular perianal fistulas differ in FC levels. Local fistula calprotectin production did not explain this difference, implying FC reflects the luminal condition. A correlation exists between scraping calprotectin levels and Crohn's disease fistula severity, which could be clinically relevant for prognostic cohorts and tailored treatment.

Introduction: Evidence suggests an association between histological inflammation and clinical relapse in ulcerative colitis (UC). Fecal calprotectin (FC) values accurately correlate with endoscopically visible inflammation. However, the diagnostic accuracy of FC for the presence of histological inflammation is unclear. We aimed to assess the relationship between FC values and endoscopic and histological outcomes in UC. Methods: The phase IV MOMENTUM trial (ClinicalTrials.gov Identifier: NCT01124149) evaluated the efficacy of multimatrix mesalamine in adult patients with mild-to-moderate UC. Patients who responded at week 8 (W8; induction) entered a maintenance treatment phase. Endoscopic and histological outcomes were assessed at W8 and week 52 (W52). Mucosal healing was defined as an endoscopic score ≤ 1. Biopsies were assessed by 2 blinded pathologists. In this post-hoc analysis we transformed the Geboes histopathology index to an ordinal score (0-13 points), excluding parameters related to chronicinflammation (ie, Geboes values ≥ 2B were used). Histological remission was defined as a Geboes score < 2B.1 (a drop in the ordinal score from > 0 to 0). Results: Data were available for 604 (94.5%) patients at W8 and 355 (95.2%) at W52. The correlation coefficients between FC and the ordinal Geboes score were 0.510 at W8 and 0.533 at W52. W8 and W52 median FC values (µg/g) were numerically lower in patients with mucosal healing (W8: 82.0 vs 412.0; W52: 43.0 vs 493.0) and histological remission (W8: 32.0 vs 219.5; W52: 24.5 vs 244.0). Area-under-the-curve (AUC) values for FC receiver operating characteristic statistics were 0.77 (W8) and 0.79 (W52) for mucosal healing. AUC values were 0.76 (W8) and 0.80 (W52) for histological remission. Optimal FC cut-off predicting mucosal healing were 250µg/g at W8 and 100µg/g at W52. Optimal FC cut-offs for histological remission were 75µg/g at W8 and 100µg/g at W52. When the analysis was limited to patients with mucosal healing, FC was still numerically higher in the presence of histological inflammation compared to histological remission at both W8 (164.0 vs. 33.0) and W52 (199.0 vs. 24.5). Conclusion: FC correlates with histological inflammation in UC, even in the absence of mucosal lesions. The optimal cut-off value for histological remission appears to be between 75 and 100µg/g.