Early Ileocecal Resection for Crohn's Disease Is Associated With Improved Long-term Outcomes Compared With Anti-Tumor Necrosis Factor Therapy: A Population-Based Cohort Study.

BACKGROUND & AIMS: Early Crohn's disease (CD) treatment involves anti-tumor necrosis factor (TNF) agents, whereas ileocecal resection (ICR) is reserved for complicated CD or treatment failure. We compared long-term outcomes of primary ICR and anti-TNF therapy for ileocecal CD. METHODS: Using cross-linked nationwide registers, we identified all individuals diagnosed with ileal or ileocecal CD between 2003 and 2018 and treated with ICR or anti-TNF agents within 1 year of diagnosis. The primary outcome was a composite of ≥1 of the following: CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD. We conducted adjusted Cox's proportional hazards regression analyses and determined the cumulative risk of different treatments after primary ICR or anti-TNF therapy. RESULTS: Of 16,443 individuals diagnosed with CD, 1279 individuals fulfilled the inclusion criteria. Of these, 45.4% underwent ICR and 54.6% received anti-TNF. The composite outcome occurred in 273 individuals (incidence rate, 110/1000 person-years) in the ICR group and in 318 individuals (incidence rate, 202/1000 person-years) in the anti-TNF group. The risk of the composite outcome was 33% lower with ICR compared with anti-TNF (adjusted hazard ratio, 0.67; 95% confidence interval, 0.54-0.83). ICR was associated with reduced risk of systemic corticosteroid exposure and CD-related surgery, but not other secondary outcomes. The proportion of individuals on immunomodulator, anti-TNF, who underwent subsequent resection, or were on no therapy 5 years post-ICR was 46.3%, 16.8%, 1.8%, and 49.7%, respectively. CONCLUSION: These data suggest that ICR may have a role as first-line therapy in CD management and challenge the current paradigm of reserving surgery for complicated CD refractory or intolerant to medications. Yet, given inherent biases associated with observational data, our findings should be interpreted and applied cautiously in clinical decision making.

Anti-Integrin αvß6 Autoantibodies Are a Novel Biomarker That Antedate Ulcerative Colitis.

BACKGROUND & AIMS: Better biomarkers for prediction of ulcerative colitis (UC) development and prognostication are needed. Anti-integrin αvß6 (anti-αvß6) autoantibodies have been described in patients with UC. We tested for the presence of anti-αvß6 antibodies in the preclinical phase of UC and studied their association with disease-related outcomes after diagnosis. METHODS: Anti-αvß6 autoantibodies were measured in 4 longitudinal serum samples collected from 82 subjects who later developed UC and 82 matched controls from a Department of Defense preclinical cohort (PREDICTS [Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects]). In a distinct, external validation cohort (Crohn's and Colitis Canada Genetic Environmental Microbial project cohort), we tested 12 pre-UC subjects and 49 matched controls. Furthermore, anti-αvß6 autoantibodies were measured in 2 incident UC cohorts (COMPASS [Comprehensive Care for the Recently Diagnosed IBD Patients], n = 55 and OSCCAR [Ocean State Crohn's and Colitis Area Registry], n = 104) and associations between anti-αvß6 autoantibodies and UC-related outcomes were defined using Cox proportional hazards model. RESULTS: Anti-αvß6 autoantibodies were significantly higher among individuals who developed UC compared with controls up to 10 years before diagnosis in PREDICTS. The anti-αvß6 autoantibody seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 time points. Anti-αvß6 autoantibodies predicted UC development with an area under the curve of at least 0.8 up to 10 years before diagnosis. The presence of anti-αvß6 autoantibodies in preclinical UC samples was validated in the GEM cohort. Finally, high anti-αvß6 autoantibodies was associated with a composite of adverse UC outcomes, including hospitalization, disease extension, colectomy, systemic steroid use, and/or escalation to biologic therapy in recently diagnosed UC. CONCLUSIONS: Anti-integrin αvß6 autoantibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.

Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.

Baseline Clinical Factors Are Associated With Risk of Complications in Crohn's Disease: Appraisal of the American Gastroenterological Association Clinical Care Pathway.

INTRODUCTION: The American Gastroenterological Association (AGA) has compiled risk factors that may be predictive of disease complications in Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate the performance of the AGA risk factors for risk stratification in UC and CD. METHODS: We included participants of 2 cohorts: the Ocean State Crohn's and Colitis Area Registry cohort and the Mayo Clinic cohort. Baseline clinical risk factors were extracted according to the AGA pathway. Our primary end point was defined as follows: (i) any inflammatory bowel disease related-hospitalization, (ii) any inflammatory bowel disease-related bowel surgery, or (iii) any progression of disease. We analyzed the association of the number of AGA risk factors with our end point. Statistical multivariable modeling was performed with Cox proportional hazards model. RESULTS: A total of 412 patients with CD were included. Comparing ≥3 risk factors with 0-1 risk factor, we found a significantly increased risk of complications in both the Ocean State Crohn's and Colitis Area Registry cohort (hazard ratio [HR] 2.75, 95% confidence interval 1.71-4.41) and Mayo Clinic cohort (HR 2.07, 95% confidence interval 1.11-3.84). Diagnosis at younger age (HR 2.07), perianal disease (HR 1.99), and B2/B3 behavior (HR 1.92) were significantly associated with disease complications. We did not observe a consistent association between number of risk factors nor any specific individual risk factors and risk of disease complications in the 265 patients with UC included. DISCUSSION: We found a significant association between the number of AGA risk factors and the risk of disease complication in CD; this association was not significant in UC. The presence of ≥ 3 risk factors in CD leads to the highest risk of complications. The AGA care pathway is a useful tool to stratify patients who are at higher risk of disease complications in patients with CD.

Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Early Use of Biologics Reduces Healthcare Costs in Crohn's Disease: Results from a United States Population-Based Cohort.

BACKGROUND: Early initiation of biologics in moderate-to-severe Crohn's disease (CD) may significantly alter disease progression, resulting in better patient outcomes. Limited real-world data exist on the impact of early biologic use in patients with CD in the United States. AIMS: We aimed to characterize biologic initiation and subsequent healthcare resource utilization (HCRU) in adults with recently diagnosed CD. METHODS: Patients with CD who initiated biologic treatment within 2 years of diagnosis (index date) were identified from medical and pharmacy claims (Merative L.P. MarketScan Database from 2010 to 2016) and classified as early (≤ 12 months post-index) or late (> 12-24 months post-index) biologic initiators. Propensity score matching balanced patient characteristics up to 1 year post-index. Differences in HCRU frequency and costs 1-2 years post-index were compared between the matched groups. RESULTS: After propensity score matching, 672 pairs of early and late biologic initiators were identified. Patients who initiated biologics early had fewer outpatient visits (15.5 vs 19.8, 95% confidence interval [CI] for difference: 2.7, 6.1) and lower total medical costs ($13,646.20 vs $22,180.70, 95% CI for difference: 4748.9, 12,320.1) 1-2 years post-index than late biologic initiators. Early biologic initiators had higher medication costs 1-2 years post-index ($33,766.30 vs $30,580.70, 95% CI: 546.1, 5825.1) but lower combined medical and medication costs ($47,412.50 vs $52,761.50, 95% CI: 801.5, 9896.40). CONCLUSIONS: While biologic treatments are costly, patients initiating biologics sooner after diagnosis appear to have better HCRU outcomes and require fewer healthcare resources at 1-2 years post-index, potentially leading to overall cost savings.

Biopsy and blood-based molecular biomarker of inflammation in IBD.

OBJECTIVE: IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments. DESIGN: Transcriptome analysis on 712 endoscopically defined inflamed (Inf) and 1778 non-inflamed (Non-Inf) intestinal biopsies (n=498 Crohn's disease, n=421 UC and 243 controls) in the Mount Sinai Crohn's and Colitis Registry were used to identify genes differentially expressed between Inf and Non-Inf biopsies and to generate a molecular inflammation score (bMIS) via gene set variance analysis. A circulating MIS (cirMIS) score, reflecting intestinal molecular inflammation, was generated using blood transcriptome data. bMIS/cirMIS was validated as indicators of intestinal inflammation in four independent IBD cohorts. RESULTS: bMIS/cirMIS was strongly associated with clinical, endoscopic and histological disease activity indices. Patients with the same histologic score of inflammation had variable bMIS scores, indicating that bMIS describes a deeper range of inflammation. In available clinical trial data sets, both scores were responsive to IBD treatment. Despite similar baseline endoscopic and histologic activity, UC patients with lower baseline bMIS levels were more likely treatment responders compared with those with higher levels. Finally, among patients with UC in endoscopic and histologic remission, those with lower bMIS levels were less likely to have a disease flare over time. CONCLUSION: Transcriptionally based scores provide an alternative objective and deeper quantification of intestinal inflammation, which could augment current clinical assessments used for disease monitoring and have potential for predicting therapeutic response and patients at higher risk of disease flares.

Is Prevention the Best Way to Modify Inflammatory Bowel Disease? How Close Are We?

Despite improved therapeutic strategies and expanding therapeutic targets, inflammatory bowel disease remains a disabling disease with potential to progress and lead to irreversible complications. Increased evidence supports the concept of a preclinical phase in inflammatory bowel disease, preceding clinical diagnosis, during which immune and inflammatory pathways are already altered. As knowledge about this prediagnosis period expands, it unlocks the possibility of disease prediction and ambition for disease prevention and interception. Targeting the early pathogenic events that promote the development of inflammatory bowel disease could prevent or attenuate disease onset and offer a true opportunity for disease modification.

Early Biologic Initiation After Chronic Pouch Inflammation Diagnosis Does Not Impact Clinical Outcomes.

Approximately 20% of patients with ulcerative colitis (UC) who undergo total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) develop chronic pouch inflammation (CPI).1 Given the involvement of the small bowel in CPI, there is no consensus on whether it should be managed more like UC or Crohn's disease (CD). Despite limited evidence, biologics are often used for CPI with clinical response rates of 20%-60% with adalimumab and infliximab, 50%-80% with ustekinumab, and 30%-70% with vedolizumab.2,3 Earlier biologic therapy has been associated with greater rates of response and favorable long-term outcomes in patients with CD, however not UC.4-7 The impact of earlier initiation of biologic therapy on CPI clinical outcomes has not been elucidated. The aim of this study was to assess whether timing of biologic initiation relative to CPI diagnosis impacts clinical and endoscopic remission.

Second-Line Biologic Therapy Following Tumor Necrosis Factor Antagonist Failure: A Real-World Propensity Score-Weighted Analysis.

BACKGROUND& AIMS: Tumor necrosis factor (TNF) antagonists often are used as first-line medications to treat moderate to severe inflammatory bowel disease (IBD), but many patients do not achieve or maintain response. Our aim was to compare the effectiveness of second-line treatments (ustekinumab, vedolizumab, or a second TNF antagonist) after TNF antagonist exposure in patients with Crohn's disease (CD) and ulcerative colitis (UC) from 2 electronic health records-based cohorts. METHODS: We identified patients with prior TNF antagonist exposure who switched to a different biologic in the Mount Sinai Health System (MSHS) electronic health records (CD, n = 527; UC, n = 165) and the Study of a Prospective Adult Research Cohort (SPARC) from the Inflammatory Bowel Disease Plexus Program of the Crohn's & Colitis Foundation (CD, n = 412; UC, n = 129). Treatment failure was defined as the composite of any IBD-related surgery, IBD-related hospitalization, new prescription of oral/intravenous corticosteroids, or need to switch to a third biologic agent. Time-to-event analysis was conducted with inverse probability of treatment-weighted data. RESULTS: Overall, treatment failure occurred in 85% of MSHS and 72% of SPARC CD patients. In SPARC, the likelihood of treatment failure was significantly lower with ustekinumab compared with vedolizumab as second-line treatment (adjusted hazard ratio, 0.66; 95% CI, 0.54-0.82; P < .001), a trend confirmed in MSHS (adjusted hazard ratio, 0.89; 95% CI, 0.77-1.04; P = .15). In both cohorts, the superiority of ustekinumab compared with vedolizumab was shown when considering treatment failure as prescription of steroids or a third biologic agent. In UC, no differences between second-line treatment groups were identified. CONCLUSIONS: In 2 independent real-world cohort settings, second-line therapy in CD with ustekinumab after TNF antagonist treatment failure was associated with a lower likelihood of treatment failure than second-line vedolizumab.

Net Remission Rates with Biologic Treatment in Crohn's Disease: A Reappraisal of the Clinical Trial Data.

Biologic therapies have greatly advanced the medical care of patients with Crohn's disease (CD); however, up to 50% of patients have no response and up to 80% fail to achieve remission.1-4 One way to investigate this treatment gap in CD is to look at the "net" remission rates in clinical trials defined as the actual percentage of patients enrolled during induction who are in remission at the end of maintenance. Indeed, most of the seminal clinical trials in CD used a "responder" methodology, where only patients who responded during induction were rerandomized to maintenance.

Preclinical Serological Signatures are Associated With Complicated Crohn's Disease Phenotype at Diagnosis.

BACKGROUND: At diagnosis, up to one-third of patients with Crohn's disease (CD) have a complicated phenotype with stricturing (B2) or penetrating (B3) behavior or require early surgery. We evaluated protein biomarkers and antimicrobial antibodies in serum archived years before CD diagnosis to assess whether complicated diagnoses were associated with a specific serological signature. METHODS: Prediagnosis serum was obtained from 201 patients with CD and 201 healthy controls. Samples were evaluated with a comprehensive panel of 1129 proteomic markers (SomaLogic) and antimicrobial antibodies. CD diagnosis and complications were defined by the International Classification of Diseases-Ninth Revision and Current Procedural Terminology codes. Cox regression models were utilized to assess the association between markers and the subsequent risk of being diagnosed with complicated CD. In addition, biological pathway and network analyses were performed. RESULTS: Forty-seven CD subjects (24%) had a B2 (n = 36) or B3 (n = 9) phenotype or CD-related surgery (n = 2) at diagnosis. Subjects presenting with complicated CD at diagnosis had higher levels of antimicrobial antibodies six years before diagnosis as compared with those diagnosed with noncomplicated CD. Twenty-two protein biomarkers (reflecting inflammatory, fibrosis, and tissue protection markers) were found to be associated with complicated CD. Pathway analysis of the altered protein biomarkers identified higher activation of the innate immune system and complement or coagulation cascades up to six years before diagnosis in complicated CD. CONCLUSIONS: Proteins and antimicrobial antibodies associated with dysregulated innate immunity, excessive adaptive response to microbial antigens, and fibrosis precede and predict a complicated phenotype at the time of diagnosis in CD patients.

Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn's Disease (EXPLORER).

BACKGROUND & AIMS: Although biologics have revolutionized the treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission rates. METHODS: EXPLORER, a phase 4, single-arm, open-label study, evaluated triple combination therapy with vedolizumab (300 mg on day 1, weeks 2 and 6, and then every 8 weeks), adalimumab (160 mg on day 2, 80 mg at week 2, then 40 mg every 2 weeks), and methotrexate (15 mg weekly) in biologic-naïve patients with newly diagnosed, moderate- to high-risk CD. Endoscopic remission at week 26 (primary end point; Simple Endoscopic Score for CD ≤2), clinical remission at weeks 10 and 26 (secondary end point; Crohn's Disease Activity Index <150), and incidences of adverse events and serious adverse events were evaluated. RESULTS: Among 55 enrolled patients, the mean CD duration was 0.4 years, the mean baseline Simple Endoscopic Score for CD was 12.6, and the mean baseline Crohn's Disease Activity Index was 265.5. At week 26, 19 patients (34.5%) were in endoscopic remission. At weeks 10 and 26, 34 (61.8%) and 30 patients (54.5%), respectively, were in clinical remission. Post hoc Bayesian analysis showed that the probabilities that triple combination therapy produced a higher endoscopic remission rate (33.5%; 95% credible interval, 22.4-45.7) than placebo (14%), vedolizumab monotherapy (27%), or adalimumab monotherapy (30%) were 99.9% or higher, 86.3%, and 71.4%, respectively. Six patients had serious adverse events. CONCLUSIONS: Combination therapy resulted in endoscopic and clinical remission at week 26 in 34.5% and 54.5% of patients, respectively, with no safety signal related to the treatment regimen. This supports further evaluation of combination therapy in CD. CLINICALTRIALS: gov number: NCT02764762.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

Humoral Immune Response and Safety of SARS-CoV-2 Vaccination in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 µg/mL (SD 67) and a median of 22 µg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Impact of Care in an Interdisciplinary Inflammatory Bowel Disease Specialty Clinic on Outcomes in Patients Insured with Medicaid.

BACKGROUND: Inflammatory bowel disease (IBD) patients are known to benefit from care delivered in a specialized, interdisciplinary setting. We aimed to evaluate the impact of this model on health outcomes, quality metrics, and health care resource utilization (HRU) in IBD patients insured with Medicaid. MATERIALS AND METHODS: In July 2017, IBD patients at our tertiary hospital were transitioned from a fellows' general gastroenterology (GI) clinic to a fellows' interdisciplinary IBD clinic. IBD patients were included if they were insured with Medicaid, had at least 1 visit in the general GI clinic between July 1, 2016 and June 30, 2017, and at least 1 visit between July 1, 2017 and June 30, 2018 in the IBD clinic. Characteristics related to patients' IBD course, overall health care maintenance, and HRU were compared. RESULTS: A total of 170 patients (51% male, mean age 39 y) were included. After the transition to the IBD clinic, use of corticosteroids (37% vs. 25%; P =0.004) and combination therapy were significantly lower (55% vs. 38%; P =0.0004), although use of high-dose biologics numerically increased (58.5% vs. 67%; P =0.05). Posttransition, patients showed significantly lower levels of mean C-reactive protein ( P =0.04). After the transition, patients attended significantly fewer outpatient GI visits ( P =0.0008) but were more often seen by other health care specialists ( P =0.0003), and experienced a numeric decrease in HRU with fewer emergency department visits, hospitalizations, and surgeries. CONCLUSIONS: Care in an interdisciplinary, IBD specialty setting is associated with significantly decreased corticosteroid use, decreased C-reactive protein levels, and improved access to ancillary services in Medicaid patients.

Mild Crohn's Disease: Definition and Management.

PURPOSE OF REVIEW: Crohn's Disease (CD) is a chronic inflammatory disease that can lead to progressive damage to the gastrointestinal tract and significant disability. Early, "top-down" biologic therapy is recommended in moderate-to-severe CD to induce remission and to prevent hospitalization and complications. However, an estimated 20-30% of patients with CD have a mild disease course and may not garner sufficient benefit from expensive, immunosuppressing agents to justify their risks. Herein, we review characteristics of patients with mild CD, the available options for disease treatment and monitoring, and future directions of research. RECENT FINDINGS: For ambulatory outpatients with low-risk, mild, ileal or ileocolonic CD, induction of remission with budesonide is recommended. For colonic CD, sulfasalazine is a reasonable choice, although other aminosalicylates have no role in the treatment of CD. No large, randomized trial has supported the use of antibiotics or antimycobacterials in the treatment of CD. Partial Enteral Nutrition and Crohn's Disease Exclusion Diets may be appropriate for inducing remission in some adult patients, with trials ongoing. Select patients with mild-to-moderate CD may benefit from maintenance therapy with azathioprines or gut specific biologics, such as vedolizumab. The role of complementary and alternative medicine is not well defined. The identification, risk stratification, and monitoring of patients with mild CD can be a challenging clinical scenario. Some patients with low risk of disease progression may be appropriate for initial induction of remission with budesonide or sulfasalazine, followed by close clinical monitoring. Future research should focus on pre-clinical biomarkers to stratify disease, novel therapies with minimal systemic immune suppression, and validation of rigorous clinical monitoring algorithms.

Approach to the Management of Recently Diagnosed Inflammatory Bowel Disease Patients: A User's Guide for Adult and Pediatric Gastroenterologists.

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic, progressive, immune-mediated diseases of adults and children that have no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in Crohn's disease, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. Although the armamentarium of IBD medications is growing, many patients will not respond to treatment, and the selection of first-line therapy is critical. Risk stratification of disease severity, based on clinical, demographic, and serologic markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics, and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end points (treat to target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Lastly, IBD therapy extends far beyond medications, and other aspects of the overall health and wellbeing of the patient are critical. These include preventive health, nutrition, and psychobehavioral support addressing patients' concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication.

Ileal Pouch Anal Anastomosis for the Management of Ulcerative Colitis Is Associated With Significant Disability.

BACKGROUND & AIMS: Disability in patients with medically refractory ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is not well understood. The aim of this study was to compare disability in patients with IPAA vs medically managed UC, and identify predictors of disability. METHODS: This was a multicenter cross-sectional study performed at 5 academic institutions in New York City. Patients with medically or surgically treated UC were recruited. Clinical and socioeconomic data were collected, and the Inflammatory Bowel Disease Disability Index (IBD-DI) was administered to eligible patients. Predictors of moderate-severe disability (IBD-DI ≥35) were assessed in univariable and multivariable models. RESULTS: A total of 94 patients with IPAA and 128 patients with medically managed UC completed the IBD-DI. Among patients with IPAA and UC, 35 (37.2%) and 30 (23.4%) had moderate-severe disability, respectively. Patients with IPAA had significantly greater IBD-DI scores compared with patients with medically managed UC (29.8 vs 17.9; P < .001). When stratified by disease activity, patients with active IPAA disease had significantly greater median IBD-DI scores compared with patients with active UC (44.2 vs 30.4; P = .01), and patients with inactive IPAA disease had significantly greater median IBD-DI scores compared with patients with inactive UC (23.1 vs 12.5; P < .001). Moderate-severe disability in patients with IPAA was associated with female sex, active disease, and public insurance. CONCLUSIONS: Patients with IPAA have higher disability scores than patients with UC, even after adjustment for disease activity. Female sex and public insurance are predictive of significant disability in patients with IPAA.