A. Hillary Steinhart

Host - microbiome interactions are central to Crohn'sdisease (CD) pathogenesis; yet the early metabolic alterations that precededisease onset remain poorly defined. To explore preclinical metabolicsignatures of CD, we analyzed baseline serum metabolomic profiles in a nestedcase-control study within the Crohn's and Colitis Canada - Genetics, Environment, Microbiome (CCC-GEM) Project, a prospective cohort of 5,122 healthyfirst-degree relatives (FDRs) of CD patients. We included 78 individuals wholater developed CD and 311 matched FDRs who remained disease-free. In an untargetedassessment of metabolomic data, we identified 63 metabolites significantlyassociated with future CD risk. Integrative analyses further identifiedmultiple associations between CD-related metabolites and proteomic markers, gutmicrobiome composition, antimicrobial antibody, fecal calprotectin andC-reactive protein. Quinolinate, a tryptophan catabolite, was elevated inindividuals who later developed CD and showed strong positive correlations withC-reactive protein, fecal calprotectin, and C-X-C motif chemokine ligand 9 (CXCL9).In contrast, higher levels of ascorbate and isocitrate were associated withreduced CD risk and were negatively correlated with C-reactive protein and CD-associated proteins.These findings identify several distinct molecular pathways that contribute toCD pathogenesis.

Tumor necrosis factor-α inhibitors, adalimumab and infliximab, are at the forefront of biologic therapy for the management of moderate-to-severe hidradenitis suppurativa, with adalimumab as currently the only approved medication for this condition. In treating patients, primary or secondary lack of response (also termed suboptimal response) is a major burden for both patients and healthcare systems and is a challenge with biologics in part owing to the development of anti-drug antibodies following treatment. To overcome this, therapeutic drug monitoring may be conducted proactively or reactively to a patient’s suboptimal response guided by measurements of trough serum drug concentrations and levels of anti-drug antibodies. While strong evidence to support the utility of therapeutic drug monitoring exists in patients with inflammatory bowel disease, current information is limited in the context of hidradenitis suppurativa. We sought to summarize the available evidence and to present the role of therapeutic drug monitoring and other dose optimization strategies in improving clinical response in patients with hidradenitis suppurativa treated with tumor necrosis factor-α inhibitors.

Golimumab is approved for the treatment of moderate-to-severely active ulcerative colitis. However, there have been no formal trials to date to assess its utility in Crohn’s disease (CD). Our aim was to determine the efficacy and safety of golimumab in patients with anti–TNF refractory CD. Patients with CD treated with golimumab between 2010 and 2017 were included in a retrospective observational study. The vast majority of patients failed 2 anti-TNFs agents. Clinical response was defined as a significant reduction in symptoms and biochemical markers of CD, and no requirement for surgery or introduction of immune-suppressants. Forty-five patients were included, with a median follow-up of 22 months (interquartile range 12–34) following initiation of golimumab. Induction and maintenance regimens were generally higher than standard dosing with first month cumulative doses of 400 mg and above in 75% of the patients. Monthly maintenance doses 200 mg was administered in 52% of patients. Clinical response at 3 months was achieved in 35/45 (77.7%) patients. The cumulative probabilities that patients with an initial response maintained their clinical response for 12 and 36 months after introduction of golimumab were 81% and 64%, respectively. Endoscopic improvement and mucosal healing at 12 months was achieved in 73% and 47% of patients, respectively. This study demonstrates the efficacy of golimumab in anti-TNF refractory CD patients. Further studies should be performed in CD to formally assess the efficacy of golimumab in a randomized controlled trial and to establish the optimal dosing regimen.

Current clinical practice guidelines suggest that patients with ulcerative colitis (UC) hospitalized because of a disease flare should be offered a normal diet, unless such a diet is not tolerated. Studies of hospitalized patients have demonstrated iatrogenic malnutrition from unjustified or inappropriate nil per os (NPO) or clear liquid diet (CLD) orders. In this study, we aim to characterize the burden of this problem in hospitalized patients with UC. We conducted a retrospective cohort study of all patients with UC admitted to the gastroenterology service or the general internal medicine service at a tertiary, academic hospital between January 2009 and December 2014, with a length of stay between 2 and 30 days. The frequency and duration of bowel rest and CLD orders was recorded, and the number of meals missed because of these orders was assessed. NPO or CLD diet orders were considered justified if the patient had intractable nausea or vomiting, pancreatitis, bowel obstruction, toxic megacolon or were awaiting endoscopy, or if alternative enteral nutrition was provided. Clinical and demographic factors associated with unjustified underfeeding were identified. A total of 187 admissions among 158 patients with UC were identified during the study period and included in the final analysis. Most admissions were to the gastroenterology service (148/187, 79.1%). The mean age at admission was 35.0 years (SD = 15), and 83/158 (52.5%) were female. The median length of stay was 8 days (interquartile range = 4–12). Registered dietician consultation was obtained in only 32 admissions (17.1%), and admission weight was recorded in only 68 (36.4%) admissions. A total of 252 NPO or CLD dietary orders were encountered in 142 admissions (75.9%). Of those, 112 orders were unjustified (44%). On average, patients with unjustified NPO or CLD orders spent 3 days on an NPO or CLD diet, which corresponded to a mean of 10 missed meals. Characteristics associated with unnecessary fasting included female gender, less frequent endoscopic disease staging, less frequent escalation of therapy to prednisone and/or biologics, and admission to a non-gastroenterology service. There is a high burden of unjustified underfeeding among hospitalized patients with UC, particularly in patients admitted without evidence of objective disease flare. This may lead to nutritional compromise in an at-risk population, and further studies are needed to assess the nutritional impact of unjustified bowel rest on patients with UC. Our findings also suggest that targeted quality improvement interventions are needed to decrease the frequency of inappropriate bowel rest among hospitalized patients with UC.