Background and aims Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option for inflammatory bowel diseases (IBD). While publications describing FMT as therapy for IBD have more than doubled since 2012, research that investigates FMT treatment efficacy has been scarce. We conducted a systematic review and meta-analysis to evaluate the efficacy of FMT as treatment for patients with IBD. Methods A systematic literature search was performed through May 2014. Inclusion criteria required FMT as primary therapeutic agent. Clinical remission (CR) and/or mucosal healing were defined as primary outcomes. Studies were excluded if they did not report clinical outcomes or included patients with infections. Results Eighteen studies (9 cohort studies, 8 case studies and 1 randomized controlled trial) were included in the analysis. 122 patients were described (79 ulcerative colitis (UC); 39 Crohn's disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow up. Among cohort studies, the pooled proportion of patients that achieved CR was 36.2% (95% CI 17.4%-60.4%), with a moderate risk of heterogeneity (Cochran's Q, P=0.011; I2 = 37%). Subgroup analyses demonstrated a pooled estimate of clinical remission of 22% (95% CI 10.4%-40.8%) for UC (Cochran's Q, P=0.37; I2 =0%) and 60.5% (95% CI 28.4%-85.6%) for CD (Cochran's Q, P=0.05; I2 = 37%). Six studies performed microbiota analysis. Conclusions This analysis suggests that FMT is a safe, but variably efficacious treatment for IBD. More randomized controlled trials are needed and should investigate frequency of FMT administration, donor selection and standardization of microbiome analysis.

Standard-of-care infliximab dosing regimens were developed prior to the routine use of therapeutic drug monitoring and identification of target concentrations. Not surprisingly, subtherapeutic infliximab concentrations in pediatric Crohn's disease (CD) are common. The primary aim was to conduct a real-world pharmacokinetic (PK) evaluation to discover blood biomarkers of rapid clearance, identify exposure targets, and a secondary aim to translate PK modeling to the clinic. In a multicenter observational study, 671 peak and trough infliximab concentrations from 78 patients with CD were analyzed with a drug-tolerant assay (Esoterix; LabCorp, Calabasas, CA). Individual area under the curve (AUC) estimates were generated as a measure of drug exposure over time. Population PK modeling (nonlinear mixed-effect modeling) identified serum albumin, antibody to infliximab, erythrocyte sedimentation rate (ESR), and neutrophil CD64 as biomarkers for drug clearance. Week 14 and week 52 biochemical remitters (fecal calprotectin < 250 µg/g) had higher infliximab exposure (AUC) throughout induction. The optimal infliximab AUC target during induction for week 14 biochemical remission was 79,348 µg*h/mL (area under the receiver operating characteristic curve (AUROC) 0.77, [0.63-0.90], 85.7% sensitive, and 64.3% specific) with those exceeding the AUC target more likely to achieve a surgery-free week 52 biochemical remission (OR 4.3,). Pretreatment predictors for subtherapeutic week 14 AUC included neutrophil CD64 > 6 (OR 4.5,), ESR > 30 mm/h (OR 3.8,), age < 10 years old (OR 4.2,), and weight < 30 kg (OR 6.6,). We created a decisionsupport PK dashboard with an iterative process and embedded the modeling program within the electronic health record. Model-informed precision dosing guided by real-world PKs is now available at the bedside in real-time.

Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow-up evaluation. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted.

Our data indicate strong agreement between PUCAI scores obtained directly from patients and those completed by physicians. Hence, a patient-based PUCAI could complement existing instruments in both clinical and research settings.

Background/AimsUlcerative colitis (UC) patients are at greater risk for the development of colorectal neoplasia. Several individual studies have demonstrated associations between severity of histologic inflammation and colorectal neoplasia. However, a comprehensive systematic review has not been completed. We performed a systematic review and meta-analysis to explore the relationship between histologic inflammation and risk for neoplasia among available observational studies.MethodsThree databases (EMBASE, MEDLINE and the Cochrane Library) were systematically searched. Studies were included if they included UC patients who underwent colonoscopic assessment and when histologic inflammation and colorectal neoplasia were both reported. Colorectal neoplasia rates were compared. Quantitative meta-analysis was attempted.ResultsFour of 1,422 records found were eligible. Results from 2 case-control studies reported a 3.5-fold increased risk for colorectal neoplasia associated with a single point increase in histologic inflammation. This result was further corroborated by one cohort study that demonstrated increased hazard ratios. The second cohort study reported outcomes for patients with normal gross endoscopy, but had increased histological inflammation when neoplasia was assessed. Finally, this study reported increased risk for neoplastic progression by histological inflammation among patients who were normal by gross endoscopic evaluation. Quantitative meta-analysis was unsuccessful due to heterogeneity between study measures.ConclusionsThere is strong evidence that histologic inflammation among patients with UC increases the risk of colorectal neoplasia. The depth and nature of assessment of additional clinical variables was varied and may have resulted in greater outcome discrepancy. Additional study related to mechanisms of inflammation-related neoplasia and therapeutic modification is needed.

In this real-world study, vedolizumab demonstrated similar efficacy and safety seen in pivotal trials, with sustained clinical response in the majority of patients. Similar rates of response were seen in UC and CD patients. 10.1093/ibd/izx067_video1izx067_Video5754037470001.

Background The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations. Methods We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn’s disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP &lt;250 µg/g, with clinical response defined as a weighted Pediatric Crohn’s Disease Activity Index &lt;12.5 or Δ&gt;17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs). Results Among 56 CD patients, ROC analysis identified an infusion 4 LCT &lt;8.06 (area under the receiver operator characteristics [AUROC], 0.934, P &lt; 0.001) and nCD64 &lt;6.12 (AUROC, 0.76, P = 0.02) as the ideal cut points for week-14 FCP biomarker remission. End of induction IFX-trough of &gt;9.4 µg/mL (AUROC, 0.799, P = 0.002) and &gt;11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP &lt;250 and FCP &lt;100, respectively. We found patients achieving end of induction trough &gt;5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels &lt;5 µg/mL (P = 0.024) with a similar median reduction in nCD64 (48% vs 20%, P = 0.031). Conclusions This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.

Background Anti-drug antibodies (ADAs) to anti-tumor necrosis factor alpha (anti-TNF) drugs are associated with increased drug clearance and loss of response. We aimed to assess the effectiveness of starting an immunomodulator (IM) drug in patients with newly detected ADAs on anti-TNF monotherapy. Methods We reviewed the medical records of pediatric patients with inflammatory bowel disease on infliximab or adalimumab monotherapy with first-time detection of significant ADAs between 2014 and 2018. Patients who started an IM within 3 months of ADA detection were compared with those who did not (No-IM). Outcomes included steroid-free clinical and biochemical remission on the same anti-TNF , anti-TNF durability, and ADA reversal. Results We identified 89 patients with ADAs: 30 IM patients and 59 No-IM patients. The initial anti-TNF was stopped shortly after ADA detection in 36% of the No-IM patients vs none of the IM patients, driving longer survival on the initial anti-TNF in the IM group (P = 0.005). At 12 months, steroid-free clinical and biochemical remission on the same anti-TNF occurred in 53.9% of the IM group vs 26.8% in the No-IM group (P = 0.025). Drug levels rose higher (P = 0.003) and ADA levels fell farther (P = 0.037) in the IM group than in the No-IM group. Baseline ADA level predicted ADA reversal in the No-IM patients with an area under the receiver operating characteristic of 0.79 (P = 0.006). An ADA level &lt;329 ng/mL had a 76.2% sensitivity and an 83.3% specificity for ADA reversal without IM. Conclusions Pediatric patients with inflammatory bowel disease on anti-TNF monotherapy who started an IM for significant ADA levels exhibited longer anti-TNF durability and a higher likelihood of steroid-free clinical and biochemical remission on the same anti-TNF. Patients not treated with an IM were unlikely to reverse ADAs &gt;329 ng/mL.