Crohn disease is a chronic idiopathic inflammatory bowel disease condition characterized by skip lesions and transmural inflammation that can affect the entire gastrointestinal tract from the mouth to the anus. For this review article, we performed a review of articles in PubMed through February 1, 2017, by using the following Medical Subject Heading terms: crohns disease, crohn's disease, crohn disease, inflammatory bowel disease, and inflammatory bowel diseases. Presenting symptoms are often variable and may include diarrhea, abdominal pain, weight loss, nausea, vomiting, and in certain cases fevers or chills. There are 3 main disease phenotypes: inflammatory, structuring, and penetrating. In addition to the underlying disease phenotype, up to a third of patients will develop perianal involvement of their disease. In addition, in some cases, extraintestinal manifestations may develop. The diagnosis is typically made with endoscopic and/or radiologic findings. Disease management is usually with pharmacologic therapy, which is determined on the basis of disease severity and underlying disease phenotype. Although the goal of management is to control the inflammation and induce a clinical remission with pharmacologic therapy, most patients will eventually require surgery for their disease. Unfortunately, surgery is not curative and patients still require ongoing therapy even after surgery for disease recurrence. Importantly, given the risks of complications from both Crohn disease and the medications used to treat the disease process, primary care physicians play an important role in optimizing the preventative care management to reduce the risk of complications.

Crohn’s disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of non-synonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2,066 CD cases and 3,633 healthy controls. We detected association signals in the LRRK2 gene that conferred CD risk (N2081D variant, P=9.5×10−10) or protection (N551K variant, tagging R1398H-associated haplotype, P=3.3×10−8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson’s disease (PD), and healthy controls revealed extensive pleiotropy, with similar genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant is associated with increased kinase activity, whereas neither N551K nor R1398H on the protective haplotype altered kinase activity. R1398H, but not N551K, increased GTPase activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.

BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD. METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 [ strongly disagree and 10 [ strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score ‡7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting. RESULTS: The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios. CONCLUSION: Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.

Infliximab infusions were accompanied by acute reactions in approximately 5% of infusions. These reactions did not seem to be true IgE-mediated type I hypersensitivity events. Using appropriate treatment protocols, these reactions were effectively treated and prevented upon retreatment in nearly all patients. Delayed reactions were rare, occurring in <1% of infusions.

OBJECTIVES Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). This has important implications for patient management and development of novel biologic therapies. The objective of this study was to perform a systematic review and meta-analysis of studies that reported clinical outcomes and IFX levels according to patients’ ATI status. METHODS MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE were searched for eligible studies. Quality assessment was undertaken using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Raw data from studies meeting inclusion criteria was pooled for meta-analysis of effect estimates. Sensitivity analysis was performed for all outcomes. Funnel plot was performed to assess for publication bias. RESULTS Thirteen studies met the inclusion criteria, and reported results in 1,378 patients with IBD. All included studies had a high risk of bias in at least one quality domain. The pooled risk ratio (RR) of loss of clinical response to IFX in patients with IBD who had ATIs was 3.2 (95 % confidence interval (CI): 2.0–4.9, P < 0.0001), when compared with patients without ATIs. This effect estimate was predominantly based on data from patients (N = 494) with Crohn’s disease (RR: 3.2, 95 % CI: 1.9–5.5, P < 0.0001). Data only from patients with ulcerative colitis (n = 86) exhibited a non-significant RR of loss of response of 2.2 (95 % CI: 0.5–9.0, P = 0.3) in those with ATIs. Heterogeneity existed between studies, in both methods of ATI detection, and clinical outcomes reported. Three studies (n = 243) reported trough serum IFX levels according to ATI status; the standardized mean difference in trough serum IFX levels between groups was −0.8 (95 % CI −1.2, −0.4, P < 0.0001). A funnel plot suggested the presence of publication bias. CONCLUSIONS The presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. Published studies on this topic lack uniform reporting of outcomes. High risk of bias was present in all the included studies.

Capsule retention occurred in 13% (95% CI 5.6%-28%) of patients with known CD, but only in 1.6% (95% CI 0.2%-10%) with suspected Crohn's. A retained capsule may indicate unsuspected strictures in Crohn's that may require an unexpected, but therapeutic, surgical intervention. Patients and physicians should be aware of these potential risks when using CE in CD.

SUMMARY Background

Background Infliximab (IFX) is effective in the treatment of inflammatory bowel disease; however, the effect is often not durable. It is unknown if proactive therapeutic concentration monitoring (TCM) of IFX improves outcomes. Methods This is a retrospective observational study examining the use of proactive TCM and titration of IFX to a target concentration for patients with inflammatory bowel disease in clinical remission at a tertiary care center. The primary aim was to describe the clinical course of patients who had proactive TCM. A secondary analysis was done to assess if this strategy was superior to the standard of care. Results Forty-eight patients were identified as having proactive TCM. Fifteen percent had an initial undetectable trough concentration. Twenty-five percent (12 of 48) of patients escalated IFX after the first proactive TCM while 15% (7 of 48) of patients de-escalated IFX therapy over the study period. A control group of 78 patients was identified. Patients who had proactive TCM had a greater probability of remaining on IFX than controls (hazard ratio, 0.3; 95% confidence interval, 0.1–0.6; log rank test; P = 0.0006). The probability of remaining on IFX was greatest for patients who achieved a trough concentration >5 μg/mL (hazard ratio, 0.03; 95% confidence interval, 0.01–0.1; P < 0.0001 versus trough <5 μg/mL). Fewer patients in the proactive TCM group stopped IFX (10% versus 31%, P = 0.009). Conclusions In this pilot observational study, proactive TCM of IFX frequently identified patients with low or undetectable trough concentrations and resulted in a greater probability of remaining on IFX.