AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases.

BACKGROUND & AIMS: Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome. METHODS: The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials. CONCLUSIONS: Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.

Effectiveness and Safety of Colonic and Capsule Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infections (rCDIs) nonresponsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients because of medical comorbidities. This study aimed to determine the safety and effectiveness of capsule FMT (cap-FMT) and colonoscopy FMT (colo-FMT) for rCDI using standardized products in a large, multicenter, prospective, real-world cohort. METHODS: Clinical outcomes and adverse events after FMT performed for rCDI at 6 sites were captured in a prospective registry. FMT was performed using 1 of 2 standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. The FMT administration route was determined by the treating physician. The rCDI cure rate was assessed at 1 and 2 months. Safety data were collected within the first 72 hours and at 1 and 2 months. Logistic regression was used to investigate factors associated with FMT failure. RESULTS: A total of 301 FMTs were performed in 269 unique patients. Two-thirds were cap-FMT. CDI cure rates were 86% (95% CI, 82%-90%) at 1 month and 81% (95% CI, 75%-86%) at 2 months. There was no difference in the 1-month or 2-month cure rate between cap-FMT and colo-FMT. Cap-FMT recipients were older and less likely to be immunosuppressed or have inflammatory bowel disease. Patient factors of older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression. In addition, post-FMT antibiotic use was associated with FMT failure at 2 months. One serious adverse event was related to colonoscopy (aspiration pneumonia), otherwise no new safety signals were identified. CONCLUSIONS: Cap-FMT using freeze-dried capsules has a similar safety and effectiveness profile compared with colo-FMT, without the procedural risks of colonoscopy. Although highly effective overall, patient selection is a key factor to optimizing FMT success.

Patients With Inflammatory Bowel Diseases and Higher Visceral Adipose Tissue Burden May Benefit From Higher Infliximab Concentrations to Achieve Remission.

INTRODUCTION: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD. METHODS: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement. RESULTS: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17-0.64], P < 0.001 and odds ratio per µg/mL: 1.11 [95% confidence interval: 1.05-1.19], P < 0.001). DISCUSSION: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission.

Cost-effectiveness of Fecal Microbiota Transplantation for First Recurrent Clostridioides difficile Infection.

BACKGROUND: Both the American College of Gastroenterology and the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America 2021 Clostridioides difficile infection (CDI) guidelines recommend fecal microbiota transplantation (FMT) for persons with multiple recurrent CDI. Emerging data suggest that FMT may have high cure rates when used for first recurrent CDI. The aim of this study was to assess the cost-effectiveness of FMT for first recurrent CDI. METHODS: We developed a Markov model to simulate a cohort of patients presenting with initial CDI infection. The model estimated the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. The model includes stratification by the severity of initial infection, estimates of cure, recurrence, and mortality. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS: When FMT is available for first recurrent CDI, the optimal cost-effective treatment strategy is fidaxomicin for initial nonsevere CDI, vancomycin for initial severe CDI, and FMT for first and subsequent recurrent CDI, with an ICER of $27 135/QALY. In probabilistic sensitivity analysis at a $100 000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrence was cost-effective 90% of the time given parameter uncertainty. CONCLUSIONS: FMT is a cost-effective strategy for first recurrent CDI. Prospective evaluation of FMT for first recurrent CDI is warranted to determine the efficacy and risk of recurrence.

Therapeutic Drug Monitoring in Practice for Inflammatory Bowel Disease.

PURPOSE OF REVIEW: To outline the development, rationale, and practical use of therapeutic drug monitoring in patients with inflammatory bowel disease. RECENT FINDINGS: Therapeutic drug monitoring is traditionally discussed in terms of a proactive or reactive approach. However, these terms are not always consistently defined and can be confusing when translating research to clinical practice. Personalized approaches incorporating clinical context and precision medicine are emerging. Personalized therapeutic drug monitoring combines a structured and proactive strategy for monitoring biologic concentrations as well as identification of antidrug antibody development or subtherapeutic dosing in the setting of loss of response. Optimizing biologic therapy can improve outcomes and avoid loss of response. Why, when, and how we measure drug troughs and anti-drug antibodies is a moving target, though what is known is that the appropriate and evidence-based use of this practice prevents adverse events and improves outcomes in patients with inflammatory bowel disease.

Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.

BACKGROUND & AIMS: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. METHODS: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. RESULTS: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. CONCLUSIONS: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.

Application of optical character recognition with natural language processing for large-scale quality metric data extraction in colonoscopy reports.

BACKGROUND AND AIMS: Colonoscopy is commonly performed for colorectal cancer screening in the United States. Reports are often generated in a non-standardized format and are not always integrated into electronic health records. Thus, this information is not readily available for streamlining quality management, participating in endoscopy registries, or reporting of patient- and center-specific risk factors predictive of outcomes. We aim to demonstrate the use of a new hybrid approach using natural language processing of charts that have been elucidated with optical character recognition processing (OCR/NLP hybrid) to obtain relevant clinical information from scanned colonoscopy and pathology reports, a technology co-developed by Cleveland Clinic and eHealth Technologies (West Henrietta, NY, USA). METHODS: This was a retrospective study conducted at Cleveland Clinic, Cleveland, Ohio, and the University of Minnesota, Minneapolis, Minnesota. A randomly sampled list of outpatient screening colonoscopy procedures and pathology reports was selected. Desired variables were then collected. Two researchers first manually reviewed the reports for the desired variables. Then, the OCR/NLP algorithm was used to obtain the same variables from 3 electronic health records in use at our institution: Epic (Verona, Wisc, USA), ProVation (Minneapolis, Minn, USA) used for endoscopy reporting, and Sunquest PowerPath (Tucson, Ariz, USA) used for pathology reporting. RESULTS: Compared with manual data extraction, the accuracy of the hybrid OCR/NLP approach to detect polyps was 95.8%, adenomas 98.5%, sessile serrated polyps 99.3%, advanced adenomas 98%, inadequate bowel preparation 98.4%, and failed cecal intubation 99%. Comparison of the dataset collected via NLP alone with that collected using the hybrid OCR/NLP approach showed that the accuracy for almost all variables was >99%. CONCLUSIONS: Our study is the first to validate the use of a unique hybrid OCR/NLP technology to extract desired variables from scanned procedure and pathology reports contained in image format with an accuracy >95%.

Clinical Performance of a Novel LIAISON Fecal Calprotectin Assay for Differentiation of Inflammatory Bowel Disease From Irritable Bowel Syndrome.

GOAL: The goal of this study was to assess the clinical performance of an investigational in vitro fecal calprotectin immunoassay for differentiating inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). BACKGROUND: Fecal calprotectin is a stool biomarker that can assist in the detection of intestinal inflammation and is utilized to identify individuals who have a higher chance of having IBD and who require further invasive tests. Current assays exhibit variable performance. MATERIALS AND METHODS: This study was a multicenter, cross-sectional analysis of prospectively collected stool samples from patients 4 years of age or older who presented with gastrointestinal (GI) symptoms and underwent colonoscopy for diagnostic confirmation. IBD was diagnosed based on clinical, endoscopic, and histologic findings. IBS was diagnosed based on Rome III Criteria and negative colonoscopy. Stool samples were extracted and tested on the DiaSorin LIAISON XL using the LIAISON Calprotectin Assay. RESULTS: A total of 240 patients (67% female) were included in the study. In total, 102 patients had IBD (54% ulcerative colitis), 67 had IBS, and 71 had other GI disorders. Median fecal calprotectin levels were significantly higher in patients with IBD [522 µg/g; 95% confidence interval (CI): 354-970 µg/g] compared with IBS (34.5 µg/g; 95% CI: 19.7-44.2 µg/g, P<0.001) and other GI disorders (28.6 µg/g; 95% CI: 18.7-40.3 µg/g, P<0.001). Receiver operating characteristic curve analysis indicated a fecal calprotectin cutoff of 94 µg/g for distinguishing IBD from other GI disorders with an area under the curve of 0.964 (sensitivity=92.2%, specificity=88.4%). CONCLUSION: The automated LIAISON Calprotectin assay brings efficient calprotectin testing to the laboratory with a time to the first result of 35 minutes and is a sensitive marker for distinguishing IBD from IBS with a cutoff of ∼100 µg/g.

Adalimumab Concentration Changes After Dose Escalation in Inflammatory Bowel Disease.

BACKGROUND: Dose escalation of adalimumab (ADA) for loss or response in inflammatory bowel disease (IBD) is a common practice. Recent data suggest improved outcomes with an ADA concentration of 12 mcg/mL, but limited data are available on the ability to achieve a target concentration. The aim of this study was to determine the expected change in serum ADA concentration after a dose escalation performed every 7 days in patients with IBD. METHODS: A retrospective cohort of patients with IBD receiving ADA was divided into every fourteen-day dosing, every 7-day dosing, and dose escalation (ie, q14 to q7 day dosing). The primary outcome was the change in ADA concentration. Multiple logistic regression was performed to identify predictors of achieving a target ADA concentration of ≥12 mcg/mL. RESULTS: Overall, 380 patients were identified, of whom 200 underwent dose escalation, 100 remained on q14 days dosing, and 80 were maintained on q7 day dosing. After dose escalation, the mean ADA concentration increased by 5.5 mcg/mL (P < 0.0001). After dose escalation, a significant proportion of patients achieved an ADA concentration ≥12 mcg/mL (P = 0.0019), as well as clinical remission (P = 0.0053). Based on multiple logistic regression, age of <46 years [odds ratio (OR): 2.4; 95% confidence interval (CI): 1.3, 4.6; P < 0.01], body mass index of <29 (OR: 0.21; 95% CI: 0.1, 0.5; P < 0.0001), and initial ADA concentration of ≥3.0 mcg/mL were found to be associated with a target ADA concentration ≥12 mcg/mL (OR: 4.76; 95% CI: 2.3, 9.7; P < 0.0001). CONCLUSIONS: The average expected increase in serum ADA concentration after dose escalation from q14 to q7 days was 5.5 mcg/mL. The initial ADA concentration, age, and body mass index may influence the ability to achieve a target ADA concentration after dose escalation.

Microscopic Colitis Is Not an Independent Risk Factor for Low Bone Density.

BACKGROUND: Microscopic colitis (MC) is a subtype of inflammatory bowel disease (IBD) with overlapping risk factors for low bone density (LBD). While LBD is a known complication of IBD, its association with MC is not well-established. AIMS: Assess the prevalence of LBD in MC compared to control populations, and evaluate if MC predicts LBD when controlling for confounders. METHODS: Retrospective, observational case control study of adult patients with pathologically confirmed MC from 2005 to 2015. Bone density measurements were abstracted from dual-energy X-ray absorptiometry (DEXA) reports, and bone density was classified using T-score: normal (T ≥ - 1.0), osteopenia (- 1.0 > T > -2.5) or osteoporosis (T ≤ - 2.5). Demographics, disease, medication history and LBD risk factors were obtained from chart review. Prevalence of LBD was compared to national and local controls. A matched control cohort to MC patients without prior diagnosis of LBD was analyzed with logistic regression to assess the relationship of MC to LBD. RESULTS: One hundred and eighteen patients with MC were identified. Osteopenia in women with MC was more prevalent compared to national controls (67% vs. 49%, p = 0.0004), and LBD was more prevalent in MC patients compared to local controls (82% vs. 55%, p < 0.0001). In MC patients without prior diagnosis of LBD matched to controls, there was a higher prevalence of osteopenia (53.2% vs. 36.7%, p = 0.04). However, after controlling for confounders, MC was not associated with LBD (OR 0.83, 95% CI 0.22, 3.16, p = 0.8). CONCLUSIONS: While LBD was more prevalent in MC patients compared to control populations, with adjustment for key confounders (including BMI, steroids, smoking, vitamin D and calcium use), MC was not an independent predictor of LBD.

Methanogen Abundance Thresholds Capable of Differentiating In Vitro Methane Production in Human Stool Samples.

BACKGROUND: Intestinal methane (CH4) gas production has been associated with a number of clinical conditions and may have important metabolic and physiological effects. AIMS: In this study, taxonomic and functional gene analyses and in vitro CH4 gas measurements were used to determine if molecular markers can potentially serve as clinical tests for colonic CH4 production. METHODS: We performed a cross-sectional study involving full stool samples collected from 33 healthy individuals. In vitro CH4 gas measurements were obtained after 2-h incubation of stool samples and used to characterize samples as CH4 positive (CH4+) and CH4 negative (CH4-; n = 10 and 23, respectively). Next, we characterized the fecal microbiota through high-throughput DNA sequencing with a particular emphasis on archaeal phylum Euryarchaeota. Finally, qPCR analyses, targeting the mcrA gene, were done to determine the ability to differentiate CH4+ versus CH4- samples and to delineate major methanogen species associated with CH4 production. RESULTS: Methanobrevibacter was found to be the most abundant methane producer and its relative abundance provides a clear distinction between CH4+ versus CH4- samples. Its sequencing-based relative abundance detection threshold for CH4 production was calculated to be 0.097%. The qPCR-based detection threshold separating CH4+ versus CH4- samples, based on mcrA gene copies, was 5.2 × 105 copies/g. CONCLUSION: Given the decreased time-burden placed on patients, a qPCR-based test on a fecal sample can become a valuable tool in clinical assessment of CH4 producing status.

Cost-effectiveness of Treatment Regimens for Clostridioides difficile Infection: An Evaluation of the 2018 Infectious Diseases Society of America Guidelines.

BACKGROUND: In 2018, the Infectious Diseases Society of America (IDSA) published guidelines for diagnosis and treatment of Clostridioides (formerly Clostridium) difficile infection (CDI). However, there is little guidance regarding which treatments are cost-effective. METHODS: We used a Markov model to simulate a cohort of patients presenting with an initial CDI diagnosis. We used the model to estimate the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the recently published 2018 IDSA guidelines. The model includes stratification by the severity of the initial infection, and subsequent likelihood of cure, recurrence, mortality, and outcomes of subsequent recurrences. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS: Use of fidaxomicin for nonsevere initial CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and fecal microbiota transplantation (FMT) for subsequent recurrence (strategy 44) cost an additional $478 for 0.009 QALYs gained per CDI patient, resulting in an ICER of $31 751 per QALY, below the willingness-to-pay threshold of $100 000/QALY. This is the optimal, cost-effective CDI treatment strategy. CONCLUSIONS: Metronidazole is suboptimal for nonsevere CDI as it is less beneficial than alternative strategies. The preferred treatment regimen is fidaxomicin for nonsevere CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and FMT for subsequent recurrence. The most effective treatments, with highest cure rates, are also cost-effective due to averted mortality, utility loss, and costs of rehospitalization and/or further treatments for recurrent CDI.

Fecal Microbiota Transplantation: Current Status in Treatment of GI and Liver Disease.

Fecal microbiota transplantation was originally introduced as a method to repair intestinal microbiota following failure of multiple treatments of recurrent Clostridiumdifficile infection with antibiotics. However, it is hypothesized that intestinal dysbiosis may contribute to the pathogenesis of many diseases, especially those involving the gastrointestinal tract. Therefore, fecal microbiota transplantation is increasingly being explored as a potential treatment that aims to optimize microbiota composition and functionality. Here, we review the current state of fecal microbiota transplantation development and applications in conditions of greatest interest to a gastroenterologist.

Amphiregulin in intestinal acute graft-versus-host disease: a possible diagnostic and prognostic aid.

Amphiregulin, a weak epidermal growth factor receptor agonist, is elevated, while epidermal growth factor, a strong epidermal growth factor receptor agonist, is low in the blood of patients with severe acute graft-versus-host disease. However, the tissue expression and function of these epidermal growth factor receptor ligands in acute graft-versus-host disease target organs is unknown. We compared by immunohistochemistry expression of amphiregulin and epidermal growth factor in archived, formalin-fixed, paraffin-embedded intestinal tissues of 48 patients with biopsy-proven gastrointestinal acute graft-versus-host disease to 3 groups: (1) 10 non-hematopoietic cell transplant normal controls, (2) 11 patients with newly diagnosed ulcerative colitis (ulcerative colitis), (3) 8 patients with a clinical diagnosis of acute graft-versus-host disease despite pathologically non-diagnostic biopsies, (4) and 10 cases of cytomegalovirus colitis. We used a semi-quantitative score of 0 (absent) through 3 (strong) to describe the intensity of immunohistochemical staining. We correlated serum and tissue amphiregulin and epidermal growth factor in patients with acute graft-versus-host disease. Gastrointestinal amphiregulin was significantly lower in acute graft-versus-host disease biopsies (median score 1), ulcerative colitis (median score 1.5), and cytomegalovirus colitis (median score 1) than in normal colon (median score 2, p = 0.004, p = 0.03, p = 0.009 respectively). Amphiregulin expression in was low in 74% of acute graft-versus-host disease cases with or without significant apoptosis. Patients with acute graft-versus-host disease exhibiting the pattern of high gastrointestinal amphiregulin but low serum amphiregulin (n = 14) had the best 1-year survival at 71%, but patients with high serum amphiregulin had poorer survival (<30%) regardless of gastrointestinal amphiregulin expression. Overall, our results lead to the hypothesis that amphiregulin is released into the circulation from damaged intestinal epithelium and stroma, although contributions from other cellular sources are likely. Low gastrointestinal amphiregulin expression by immunohistochemistry may be further studied for its utility in the pathologic acute graft-versus-host disease diagnosis without classic apoptotic changes.

Maintenance Adalimumab Concentrations Are Associated with Biochemical, Endoscopic, and Histologic Remission in Inflammatory Bowel Disease.

BACKGROUND: A treat-to-target therapeutic approach is emerging as the new standard of care for treating inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). AIMS: We aimed to investigate the association of serum adalimumab concentrations during maintenance therapy with biochemical, endoscopic, and histologic remission in IBD. METHODS: This retrospective multicenter study included consecutive IBD patients on adalimumab maintenance therapy who had a C-reactive protein (CRP) within 1 week and/or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between July 2013 and December 2016. Biochemical remission was defined as a normal CRP (≤ 5 mg/L). Endoscopic remission was defined as the absence of any ulceration/erosion or a Rutgeerts score of ≤ i1 for patients with an ileocolonic resection for CD and a Mayo endoscopic score of ≤ 1 for UC. Histologic remission was defined as the absence of any sign of active inflammation. Adalimumab concentrations were measured using the homogeneous mobility shift assay. RESULTS: Ninety-one CRP levels and 72 colonoscopies from 98 IBD patients [CD: n = 72 (73%)] were evaluated. Based on receiver operating characteristic analyses, we identified an adalimumab concentration threshold of 11.8, 12, and 12.2 µg/mL in CD and 10.5, 16.2, and 16.2 µg/mL in UC to stratify patients with or without biochemical, endoscopic, or histologic remission, respectively. Adalimumab concentrations ≥ 12 µg/mL (OR 8; 95% CI 2-31.9; p = 0.003) and ≥ 12.2 µg/mL (OR 9.6; 95% CI 1.7-56.1; p = 0.012) were independently associated with endoscopic and histologic remission in CD, respectively. CONCLUSIONS: This study demonstrates that higher maintenance adalimumab concentrations are associated with objective therapeutic outcomes in IBD.