Real-world clinical outcomes and healthcare costs in patients with Crohn's disease treated with vedolizumab versus ustekinumab in the United States.

OBJECTIVE: To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn's disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. METHODS: A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009-30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection-related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. RESULTS: 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection-related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = -$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. CONCLUSIONS: In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Crohn's disease (CD) causes inflammation in the digestive system. Vedolizumab (VDZ) and ustekinumab (UST) are therapies for patients with CD. Little is known about the clinical outcomes and healthcare costs of VDZ versus UST in the real world in the United States. We used health claims data and found that VDZ and UST had comparable real-world clinical outcomes. After 12 months of treatment, the proportions of patients with CD who stayed on treatment and those who needed to increase therapy dose were similar with VDZ and UST. The rate of infection was also similar between the two groups of patients. However, the monthly healthcare costs were $5051 less for patients treated with VDZ than with UST. This was mainly due to the lower cost of VDZ, which was almost half of that of UST. The lower treatment costs with VDZ may provide substantial savings for the healthcare system and patients specifically. Future cost-effectiveness studies on VDZ and UST are needed to aid treatment selection for patients with CD.

Machine learning to understand risks for severe COVID-19 outcomes: a retrospective cohort study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US health-care system.

BACKGROUND: In the context of immune-mediated inflammatory diseases (IMIDs), COVID-19 outcomes are incompletely understood and vary considerably depending on the patient population studied. We aimed to analyse severe COVID-19 outcomes and to investigate the effects of the pandemic time period and the risks associated with individual IMIDs, classes of immunomodulatory medications (IMMs), chronic comorbidities, and COVID-19 vaccination status. METHODS: In this retrospective cohort study, clinical data were derived from the electronic health records of an integrated health-care system serving patients in 51 hospitals and 1085 clinics across seven US states (Providence St Joseph Health). Data were observed for patients (no age restriction) with one or more IMID and for unmatched controls without IMIDs. COVID-19 was identified with a positive nucleic acid amplification test result for SARS-CoV-2. Two timeframes were analysed: March 1, 2020-Dec 25, 2021 (pre-omicron period), and Dec 26, 2021-Aug 30, 2022 (omicron-predominant period). Primary outcomes were hospitalisation, mechanical ventilation, and mortality in patients with COVID-19. Factors, including IMID diagnoses, comorbidities, long-term use of IMMs, and COVID-19 vaccination status, were analysed with multivariable logistic regression (LR) and extreme gradient boosting (XGB). FINDINGS: Of 2 167 656 patients tested for SARS-CoV-2, 290 855 (13·4%) had confirmed COVID-19: 15 397 (5·3%) patients with IMIDs and 275 458 (94·7%) without IMIDs. In the pre-omicron period, 169 993 (11·2%) of 1 517 295 people who were tested for COVID-19 tested positive, of whom 23 330 (13·7%) were hospitalised, 1072 (0·6%) received mechanical ventilation, and 5294 (3·1%) died. Compared with controls, patients with IMIDs and COVID-19 had higher rates of hospitalisation (1176 [14·6%] vs 22 154 [13·7%]; p=0·024) and mortality (314 [3·9%] vs 4980 [3·1%]; p<0·0001). In the omicron-predominant period, 120 862 (18·6%) of 650 361 patients tested positive for COVID-19, of whom 14 504 (12·0%) were hospitalised, 567 (0·5%) received mechanical ventilation, and 2001 (1·7%) died. Compared with controls, patients with IMIDs and COVID-19 (7327 [17·3%] of 42 249) had higher rates of hospitalisation (13 422 [11·8%] vs 1082 [14·8%]; p<0·0001) and mortality (1814 [1·6%] vs 187 [2·6%]; p<0·0001). Age was a risk factor for worse outcomes (adjusted odds ratio [OR] from 2·1 [95% CI 2·0-2·1]; p<0·0001 to 3·0 [2·9-3·0]; p<0·0001), whereas COVID-19 vaccination (from 0·082 [0·080-0·085]; p<0·0001 to 0·52 [0·50-0·53]; p<0·0001) and booster vaccination (from 2·1 [2·0-2·2]; p<0·0001 to 3·0 [2·9-3·0]; p<0·0001) status were associated with better outcomes. Seven chronic comorbidities were significant risk factors during both time periods for all three outcomes: atrial fibrillation, coronary artery disease, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, chronic liver disease, and cancer. Two IMIDs, asthma (adjusted OR from 0·33 [0·32-0·34]; p<0·0001 to 0·49 [0·48-0·51]; p<0·0001) and psoriasis (from 0·52 [0·48-0·56] to 0·80 [0·74-0·87]; p<0·0001), were associated with a reduced risk of severe outcomes. IMID diagnoses did not appear to be significant risk factors themselves, but results were limited by small sample size, and vasculitis had high feature importance in LR. IMMs did not appear to be significant, but less frequently used IMMs were limited by sample size. XGB outperformed LR, with the area under the receiver operating characteristic curve for models across different time periods and outcomes ranging from 0·77 to 0·92. INTERPRETATION: Our results suggest that age, chronic comorbidities, and not being fully vaccinated might be greater risk factors for severe COVID-19 outcomes in patients with IMIDs than the use of IMMs or the IMIDs themselves. Overall, there is a need to take age and comorbidities into consideration when developing COVID-19 guidelines for patients with IMIDs. Further research is needed for specific IMIDs (including IMID severity at the time of SARS-CoV-2 infection) and IMMs (considering dosage and timing before a patient's first COVID-19 infection). FUNDING: Pfizer, Novartis, Janssen, and the National Institutes of Health.

Achievement of Clinical, Endoscopic, and Histological Outcomes in Patients with Ulcerative Colitis Treated with Etrasimod, and Association with Faecal Calprotectin and C-reactive Protein: Results From the Phase 2 OASIS Trial.

BACKGROUND AND AIMS: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis [UC]. This post-hoc analysis of the phase 2 OASIS trial [NCT02447302] evaluated its efficacy for endoscopic improvement-histologic remission [EIHR] and assessed correlation between faecal calprotectin [FCP] and C-reactive protein [CRP] levels with efficacy outcomes. METHODS: In total, 156 adults with moderately to severely active UC received once-daily etrasimod (1 mg [n = 52]; 2 mg [n = 50]) or placebo [n = 54] for 12 weeks. Clinical, endoscopic, and histologic variables were evaluated at baseline and Week 12. EIHR was defined as achievement of endoscopic improvement [endoscopic subscore ≤ 1, without friability] and histologic remission [Geboes score < 2.0]. Outcomes included the relationships between FCP and CRP concentration and clinical, endoscopic, and histologic variables. RESULTS: Achievement of EIHR was significantly higher in patients who received etrasimod 2 mg versus placebo [19.5% vs 4.1%; Mantel-Haenszel estimated difference, 15.4%; p = 0.010]. In the etrasimod 2 mg group, median FCP and CRP levels at Week 12 were significantly lower in patients who achieved clinical remission, endoscopic improvement, histologic remission, and EIHR versus patients who did not [all p < 0.05]. An FCP concentration cutoff of 250 µg/g achieved optimum sensitivity and specificity for efficacy, including EIHR [0.857 and 0.786, respectively; κ coefficient, 0.3584]. Higher proportions of patients with FCP ≤ 250 µg/g achieved efficacy outcomes at Week 12 versus patients with FCP > 250 µg/g. CONCLUSIONS: Etrasimod was effective for inducing EIHR in patients with UC. FCP and CRP may be useful, noninvasive biomarkers to monitor treatment response. CLINICALTRIALS.GOV NUMBER: NCT02447302.

Use of a Novel Artificial Intelligence System Leads to the Detection of Significantly Higher Number of Adenomas During Screening and Surveillance Colonoscopy: Results From a Large, Prospective, US Multicenter, Randomized Clinical Trial.

INTRODUCTION: Adenoma per colonoscopy (APC) has recently been proposed as a quality measure for colonoscopy. We evaluated the impact of a novel artificial intelligence (AI) system, compared with standard high-definition colonoscopy, for APC measurement. METHODS: This was a US-based, multicenter, prospective randomized trial examining a novel AI detection system (EW10-EC02) that enables a real-time colorectal polyp detection enabled with the colonoscope (CAD-EYE). Eligible average-risk subjects (45 years or older) undergoing screening or surveillance colonoscopy were randomized to undergo either CAD-EYE-assisted colonoscopy (CAC) or conventional colonoscopy (CC). Modified intention-to-treat analysis was performed for all patients who completed colonoscopy with the primary outcome of APC. Secondary outcomes included positive predictive value (total number of adenomas divided by total polyps removed) and adenoma detection rate. RESULTS: In modified intention-to-treat analysis, of 1,031 subjects (age: 59.1 ± 9.8 years; 49.9% male), 510 underwent CAC vs 523 underwent CC with no significant differences in age, gender, ethnicity, or colonoscopy indication between the 2 groups. CAC led to a significantly higher APC compared with CC: 0.99 ± 1.6 vs 0.85 ± 1.5, P = 0.02, incidence rate ratio 1.17 (1.03-1.33, P = 0.02) with no significant difference in the withdrawal time: 11.28 ± 4.59 minutes vs 10.8 ± 4.81 minutes; P = 0.11 between the 2 groups. Difference in positive predictive value of a polyp being an adenoma among CAC and CC was less than 10% threshold established: 48.6% vs 54%, 95% CI -9.56% to -1.48%. There were no significant differences in adenoma detection rate (46.9% vs 42.8%), advanced adenoma (6.5% vs 6.3%), sessile serrated lesion detection rate (12.9% vs 10.1%), and polyp detection rate (63.9% vs 59.3%) between the 2 groups. There was a higher polyp per colonoscopy with CAC compared with CC: 1.68 ± 2.1 vs 1.33 ± 1.8 (incidence rate ratio 1.27; 1.15-1.4; P < 0.01). DISCUSSION: Use of a novel AI detection system showed to a significantly higher number of adenomas per colonoscopy compared with conventional high-definition colonoscopy without any increase in colonoscopy withdrawal time, thus supporting the use of AI-assisted colonoscopy to improve colonoscopy quality ( ClinicalTrials.gov NCT04979962).

Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension.

BACKGROUNDS AND AIMS: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis. METHODS: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates. RESULTS: This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently. CONCLUSIONS: Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.

Early recapture of response with tofacitinib 10 mg twice daily in patients with ulcerative colitis in OCTAVE Open following dose reduction or treatment interruption in OCTAVE Sustain.

BACKGROUND AND AIM: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis. These post hoc analyses evaluated early improvement in patient-reported outcomes with tofacitinib 10 mg twice daily (BID) in OCTAVE Open among patients with ulcerative colitis who experienced treatment failure with placebo (retreatment subpopulation) or tofacitinib 5 mg BID (dose escalation subpopulation) during maintenance. METHODS: Endpoints based on Mayo subscores (rectal bleeding improvement, stool frequency improvement, and symptomatic [both rectal bleeding and stool frequency] improvement) were analyzed overall and by prior tumor necrosis factor inhibitor (TNFi) failure status from month (M)1-M6 in OCTAVE Open. Changes from baseline in partial Mayo score, rectal bleeding subscore, and stool frequency subscore at M1 were also analyzed, by M2 clinical response status. RESULTS: At M1 of OCTAVE Open, 83.2%, 70.3%, and 64.4% of patients in the retreatment subpopulation (n = 101) had rectal bleeding improvement, stool frequency improvement, and symptomatic improvement, respectively. Corresponding values in the dose escalation subpopulation (n = 57) were 59.6%, 50.9%, and 38.6%. For both subpopulations, results were generally consistent regardless of prior TNFi failure. In the dose escalation subpopulation, mean decrease from baseline in partial Mayo score and stool frequency subscore at M1 was greater in patients with versus without a clinical response at M2. CONCLUSIONS: Rectal bleeding improvement and stool frequency improvement were achieved by M1 in many patients receiving tofacitinib 10 mg BID in both subpopulations, with no apparent difference by prior TNFi failure. Analyses were limited by small sample sizes for some subgroups.

Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies.

BACKGROUND: Etrasimod, a once-daily, oral, sphingosine 1-phosphate (S1P) receptor modulator that selectively activates S1P receptor subtypes 1, 4, and 5, with no detectable activity on S1P2,3, is in development for the treatment of immune-mediated diseases, including ulcerative colitis. In these two phase 3 trials, we aimed to evaluate the safety and efficacy of etrasimod in adult patients with moderately to severely active ulcerative colitis. METHODS: In two independent randomised, multicentre, double-blind, placebo-controlled, phase 3 trials, ELEVATE UC 52 and ELEVATE UC 12, adults with active moderate-to-severe ulcerative colitis and an inadequate or loss of response or intolerance to at least one approved ulcerative colitis therapy were randomly assigned (2:1) to once-daily oral etrasimod 2 mg or placebo. Patients in ELEVATE UC 52 were enrolled from 315 centres in 40 countries. Patients in ELEVATE UC 12 were enrolled from 407 centres in 37 countries. Randomisation was stratified by previous exposure to biologicals or Janus kinase inhibitor therapy (yes vs no), baseline corticosteroid use (yes vs no), and baseline disease activity (modified Mayo score [MMS]; 4-6 vs 7-9). ELEVATE UC 52 comprised a 12-week induction period followed by a 40-week maintenance period with a treat-through design. ELEVATE UC 12 independently assessed induction at week 12. The primary efficacy endpoints were the proportion of patients with clinical remission at weeks 12 and 52 in ELEVATE UC 52 and week 12 in ELEVATE UC 12. Safety was evaluated in both trials. ELEVATE UC 52 and ELEVATE UC 12 were registered with ClinicalTrials.gov, NCT03945188 and NCT03996369, respectively. FINDINGS: Patients in ELEVATE UC 52 were enrolled between June 13, 2019, and Jan 28, 2021. Patients in ELEVATE UC 12 were enrolled between Sept 15, 2020, and Aug 12, 2021. ELEVATE UC 52 and ELEVATE UC 12 screened 821 patients and 606 patients, respectively, with 433 and 354 subsequently undergoing random assignment. The full analysis set of ELEVATE UC 52 comprised 289 patients assigned to etrasimod and 144 to placebo. In ELEVATE UC 12, 238 patients were assigned to etrasimod and 116 to placebo. In ELEVATE UC 52, a significantly greater proportion of patients in the etrasimod group achieved clinical remission compared with patients in the placebo group at completion of the 12-week induction period (74 [27%] of 274 patients vs ten [7%] of 135 patients; p<0·0001) and at week 52 (88 [32%] of 274 patients vs nine [7%] of 135 patients; p<0·0001). In ELEVATE UC 12, 55 (25%) of 222 patients in the etrasimod group had clinical remission compared with 17 (15%) of 112 patients in the placebo group at the end of the 12-week induction period (p=0·026). Adverse events were reported in 206 (71%) of 289 patients in the etrasimod group and 81 (56%) of 144 patients in the placebo group in ELEVATE UC 52 and 112 (47%) of 238 patients in the etrasimod group and 54 (47%) of 116 patients in the placebo group in ELEVATE UC 12. No deaths or malignancies were reported. INTERPRETATION: Etrasimod was effective and well tolerated as an induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Etrasimod is a treatment option with a unique combination of attributes that might address the persistent unmet needs of patients with ulcerative colitis. FUNDING: Arena Pharmaceuticals.

Real-world characteristics, treatment experiences and corticosteroid utilisation of patients treated with tofacitinib for moderate to severe ulcerative colitis.

BACKGROUND: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We aimed to describe the real-world treatment experience and corticosteroid utilisation of patients treated with tofacitinib in a US claims database. METHODS: Patients with a UC diagnosis who initiated tofacitinib, vedolizumab or tumour necrosis factor inhibitor (TNFi) treatment between May 2018 and July 2019 were identified from the Optum Research Database. Demographic and clinical characteristics of patients who initiated tofacitinib, vedolizumab or TNFi were described. Oral corticosteroid use prior to and following tofacitinib initiation was evaluated. Tofacitinib adherence (proportion of days covered) and continuation was assessed for 6 months following initiation. Analyses were descriptive and stratified by prior biologic use (naïve, 1 or ≥ 2; minimum of 12 months prior to tofacitinib initiation). RESULTS: Among patients initiating tofacitinib (N = 225), mean age was 45.6 (SD 16.5) years and 50.2% were female. Of these, 43 (19.1%) patients were biologic-naïve and 182 (80.9%) had prior biologic use (92 [40.9%], 1 prior biologic; 90 [40.0%], ≥ 2 prior biologics). Among patients with 1 prior biologic, 82.6% were previously treated with a TNFi. Among patients with ≥ 2 prior biologics, 54.4% were previously treated with vedolizumab and a TNFi, 16.7% with two TNFi and 28.9% with ≥ 3 prior biologics. In the 6 months prior to tofacitinib initiation, 65.8% of patients had received oral corticosteroids (74.4%, 60.9% and 66.7% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively). The proportion of patients with ongoing oral corticosteroid use 3-6 months after tofacitinib initiation decreased to 13.3% (9.3%, 18.5% and 10.0% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively), and 19.6% of patients discontinued oral corticosteroid use during the 6 months after tofacitinib initiation. Overall, tofacitinib adherence, as determined by the mean proportion of days covered during the 6-month follow-up, was 0.7 (median 0.8). During the 6-month follow-up, 84.9% of patients continued tofacitinib. CONCLUSIONS: Among patients with UC initiating tofacitinib, the majority had prior biologic use. Tofacitinib adherence was high, discontinuation was low and oral corticosteroid utilisation decreased irrespective of prior biologic use. Further research with longer follow-up and a larger sample size is required.

Usefulness of Fluoroscopy for Endoscopic Balloon Dilation of Crohn's Disease-Related Strictures.

BACKGROUND: Fluoroscopy is often used for endoscopic balloon dilation (EBD) of Crohn's disease (CD)-related strictures. However, its benefit remains unclear. AIMS: To compare EBD with (EBDF) and without (EBDNF) fluoroscopic guidance in CD patients with strictures. METHODS: Single-center, nested, case-control retrospective study of EBD for CD-related strictures. Technical and clinical success and safety outcomes were compared between EBDF and EBDNF. RESULTS: A total of 122 strictures in 114 CD patients who underwent EBD from 2010 to 2018 at a single institution were reviewed (44 patients EBDF vs. 70 EBDNF). Esophagogastroduodenoscopy was the approach in 8 strictures, colonoscopy in 86, and deep enteroscopy in 28. There were no significant differences in the rates of technical and clinical success, need for repeat dilation and surgery between the two groups, although the mean maximal endoscopic balloon diameter was larger in the EBDNF group (17.1 ± 1.9 vs. 14.1 ± 2.5; p < 0.001). There was one perforation in EBDF and no serious complications in EBDNF. In multivariate analysis, balloon size < 15 mm (odds ratio [OR] 6.388; 95% CI 1.96-20.79; p = 0.002) and multiple strictures (OR 3.897; 95% CI 1.09-14.01; p = 0.037) were associated with repeat EBD, and age < 50 years (OR 7.178; 95% CI 1.38-37.44; p = 0.019) and small bowel (vs. colon) location (OR 7.525; 95% CI 1.51-37.47; p = 0.014) were associated with the need for surgery after EBD. CONCLUSIONS: EBD for CD-related strictures can be performed safely and effectively without fluoroscopic guidance. Balloon size, patient age, stricture location, and multiplicity are associated with clinical success and avoidance of surgery.

Role of hospitalization for inflammatory bowel disease in the post-biologic era.

Treatment for inflammatory bowel disease (IBD) often requires specialized care. While much of IBD care has shifted to the outpatient setting, hospitalizations remain a major site of healthcare utilization and a sizable proportion of patients with inflammatory bowel disease require hospitalization or surgery during their lifetime. In this review, we approach IBD care from the population-level with a specific focus on hospitalization for IBD, including the shifts from inpatient to outpatient care, the balance of emergency and elective hospitalizations, regionalization of specialty IBD care, and contribution of surgery and endoscopy to hospitalized care.

Nurse-Administered Propofol Continuous Infusion Sedation: A New Paradigm for Gastrointestinal Procedural Sedation.

INTRODUCTION: Nurse-Administered Propofol Continuous Infusion Sedation (NAPCIS) is a new nonanesthesia propofol delivery method for gastrointestinal endoscopy. NAPCIS is adopted from the computer-assisted propofol sedation (CAPS) protocol. We evaluated the effectiveness, efficiency, and safety of NAPCIS in low-risk subjects. METHODS: Between December 2016 and July 2017, patients who underwent esophagogastroduodenoscopy or colonoscopy with NAPCIS at our center were compared against 2 historical control groups of similar patients who had undergone procedures with CAPS or midazolam and fentanyl (MF) sedation. RESULTS: The mean age of the NAPCIS cohort (N = 3,331) was 55.2 years (45.8% male) for 945 esophagogastroduodenoscopies and 57.8 years (48.7% male) for 2,386 colonoscopies. The procedural success rates with NAPCIS were high (99.1%-99.2%) and similar to those seen in 3,603 CAPS (98.8%-99.0%) and 3,809 MF (99.0%-99.3%) controls. NAPCIS recovery times were shorter than both CAPS and MF (24.8 vs 31.7 and 52.4 minutes, respectively; P < 0.001). On arrival at the recovery unit, 86.6% of NAPCIS subjects were recorded as "Awake" compared with 82.8% of CAPS and 40.8% of MF controls (P < 0.001). Validated clinician and patient satisfaction scores were generally higher for NAPCIS compared with CAPS and MF subjects. For NAPCIS, there were only 4 cases of oxygen desaturation requiring transient mask ventilation and no serious sedation-related complications. These low complication rates were similar to those seen with CAPS (8 cases of mask ventilation) and MF (3 cases). DISCUSSION: NAPCIS seems to be a safe, effective, and efficient means of providing moderate sedation for upper endoscopy and colonoscopy in low-risk patients.

Endoscopic evaluation of surgically altered bowel in inflammatory bowel disease: a consensus guideline from the Global Interventional Inflammatory Bowel Disease Group.

The majority of patients with Crohn's disease and a proportion of patients with ulcerative colitis will ultimately require surgical treatment despite advances in diagnosis, therapy, and endoscopic interventions. The surgical procedures that are most commonly done include bowel resection with anastomosis, strictureplasty, faecal diversion, and ileal pouch. These surgical treatment modalities result in substantial alterations in bowel anatomy. In patients with inflammatory bowel disease, endoscopy plays a key role in the assessment of disease activity, disease recurrence, treatment response, dysplasia surveillance, and delivery of endoscopic therapy. Endoscopic evaluation and management of surgically altered bowel can be challenging. This consensus guideline delineates anatomical landmarks and endoscopic assessment of these landmarks in diseased and surgically altered bowel.

Long-term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results from the Open-label Extension of the OASIS Study.

BACKGROUND AND AIMS: Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator. In a phase 2, randomised, double-blind, placebo-controlled trial in adults with moderately-to-severely active ulcerative colitis [OASIS], etrasimod 2 mg provided significant benefit versus placebo and was generally well tolerated. This open-label extension [OLE] evaluated safety and efficacy of etrasimod for up to 52 weeks. METHODS: In OASIS, 156 patients received etrasimod 1 mg, etrasimod 2 mg, or placebo, once daily for 12 weeks. After completing OASIS, patients could enrol in the OLE and receive etrasimod 2 mg for an additional 34-40 weeks. RESULTS: In all, 118 patients enrolled in the OLE; 112 patients received etrasimod 2 mg at any point and were evaluated for safety and efficacy. A total of 92 [82%] patients who received etrasimod 2 mg in the OLE completed the study. Treatment-emergent adverse events occurred in 60% [67/112] of patients receiving etrasimod 2 mg at any time, most commonly worsening ulcerative colitis and anaemia; 94% of adverse events were mild/moderate. At end of treatment, 64% of patients met the criteria for clinical response, 33% for clinical remission, and 43% for endoscopic improvement. Week 12 clinical response, clinical remission, or endoscopic improvement was maintained to end of treatment in 85%, 60%, or 69% of patients, respectively. Steroid-free clinical remission occurred in 22% of overall patients. CONCLUSIONS: In this long-term extension study, etrasimod 2 mg demonstrated a favourable safety profile. Most patients with clinical response, clinical remission, or endoscopic improvement at Week 12 maintained that status to end of treatment.

Nurse-Administered Propofol Continuous Infusion Sedation for Gastrointestinal Endoscopy in Patients Who Are Difficult to Sedate.

BACKGROUND & AIMS: Patients who chronically use alcohol, marijuana, or opioids, or suffer from post-traumatic stress disorder (PTSD), can be difficult to sedate with midazolam and fentanyl, and often are referred for monitored anesthesia care during endoscopy. Nurse-administered propofol continuous infusion sedation (NAPCIS), which confers the benefit of propofol-based sedation without the added expense of anesthesia, is effective and safe for sedation of healthy patients. We investigated whether NAPCIS also is effective for patients who are difficult to sedate. METHODS: We performed a retrospective study of patients who underwent upper endoscopy or colonoscopy with NAPCIS at a single center from January 2018 through April 2018. We reviewed records from patients who were heavy users of alcohol (n = 105), daily users of marijuana (n = 267) or opioids (n = 178), had a diagnosis of PTSD (n = 91), or were none of these (controls, n = 786). We compared mean fentanyl and propofol doses (adjusted for body weight), procedure and recovery times, procedure success rates, and adverse events. RESULTS: Compared with the controls, the marijuana group required higher mean adjusted sedative doses for colonoscopies (0.6 vs 0.4 mcg/kg fentanyl and 5.0 vs 4.7 mg/kg propofol; P ≤ .025 for both) and upper endoscopies (0.8 vs 0.3 mcg/kg fentanyl and 3.7 vs 3.2 mg/kg propofol; P ≤ .021 for both), the PTSD group required a higher dose of fentanyl for colonoscopies (0.6 vs 0.4 mcg/kg; P = .009), and the alcohol group required a higher dose of fentanyl for upper endoscopies (0.7 vs 0.3 mcg/kg; P < .001). Procedure success rates were high (95.1%-100%) and did not differ significantly between the difficult-to-sedate groups and controls; mean procedure times (7.0-9.0 minutes for upper endoscopies, 21.1-22.9 minutes for colonoscopies) and recovery times (22.5-29.6 minutes) also were similar among groups. Upper endoscopies were associated with lower sedative doses and shorter procedure and recovery times than colonoscopies. Sedation-related adverse events were rare in all groups (only 26 cases total), and there were no serious complications or deaths. CONCLUSIONS: NAPCIS seems to be a safe and effective means of providing sedation for endoscopy to patients who may be difficult to sedate owing to alcohol, marijuana, or opioid use, or PTSD.

Advanced neoplasia detection using chromoendoscopy and white light colonoscopy for surveillance in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Chromoendoscopy (CE) has been shown to be superior to white light endoscopy (WLE) for neoplasia detection in inflammatory bowel disease (IBD). We aimed to compare the yield of CE and WLE for the detection of overall neoplasia and advanced neoplasia in IBD. METHODS: Patients who underwent surveillance colonoscopy from 1999 to 2017 were identified from our IBD database. CE procedures were compared with their respective WLE controls in a paired comparison, and frequency of all neoplasia, advanced neoplasia, and serrated neoplasia was assessed for both targeted and random biopsies. RESULTS: A total of 290 procedures performed in 98 individuals were identified with a median follow-up 4 years (median 3 colonoscopies/patient). CE and WLE were performed in 159 and 131 episodes, respectively. CE detected neoplasia in 40.9% of colonoscopies versus 23.7% with WLE (P= 0.002). In addition, CE detected more advanced neoplasia (18.2% vs. 6.1%, P= 0.002) and serrated lesions (14.5% vs. 6.1%, P= 0.022). Significantly fewer samples were obtained per procedure with CE (14.9 ± 9.7 vs. 20.9 ± 11.1, P< 0.001). Cancer was diagnosed in 2 cases. CONCLUSIONS: CE has a higher detection rate than WLE for advanced neoplasia and serrated lesions in patients with IBD under surveillance. Further prospective studies evaluating the impact of CE on decreasing the risk of interval cancer and colectomy in IBD patients are warranted.

Economic Outcomes of Inflammatory Bowel Disease Patients Switching to a Second Anti-Tumor Necrosis Factor or Vedolizumab.

Background: Anti-tumor necrosis factor (TNF) therapies have been the mainstay of inflammatory bowel disease (IBD) treatment for nearly 2 decades. Therapies with novel mechanisms of action have been recently developed. This study compared healthcare resource utilization (HRU) and costs incurred while switching from an initial anti-TNF to another anti-TNF versus switching to vedolizumab. Methods: Adults with IBD who switched from initial anti-TNF to another anti-TNF or vedolizumab were identified from Truven MarketScan claims database (January 1, 2000-September 30, 2017). Patient characteristics were assessed during the 6-month period before the initiation date of the switched-to treatment (index date). Adjusted analyses of all-cause and disease-related HRU and costs during the 6-month period after the index date (study period) were performed. Anti-TNF and vedolizumab switchers with Crohn's disease (CD) and ulcerative colitis (UC) were separately compared. Results: A total of 502 vedolizumab, 1708 adalimumab, 755 infliximab, and 703 other switchers with CD and 461, 428, 311, and 148 with UC, respectively, were identified. Patient demographics were similar across cohorts. Total all-cause costs were significantly higher for vedolizumab than adalimumab, infliximab, and certolizumab switchers in the CD cohort and adalimumab and infliximab in the UC cohort. In both cohorts, adalimumab and other switchers had fewer all-cause and IBD-related outpatient visits than vedolizumab switchers. Conclusions: CD/UC patients who switched to vedolizumab from initial anti-TNF had higher total and treatment costs than patients who switched to another anti-TNF, except for UC patients who switched to golimumab. Prospective studies should be conducted to confirm these findings.

Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC). METHODS: In a phase 2, proof-of-concept, double-blind, parallel-group study, adult outpatients with modified Mayo Clinic scores (MCSs) (stool frequency, rectal bleeding, and endoscopy findings) of 4-9, endoscopic subscores of 2 or more, and rectal bleeding subscores of 1 or more were randomly assigned to groups given once-daily etrasimod 1 mg (n = 52), etrasimod 2 mg (n = 50), or placebo (n = 54) for 12 weeks. The study was performed from October 15, 2015, through February 14, 2018, at 87 centers in 17 countries. The primary endpoint was an increase in the mean improvement in modified MCS from baseline to week 12. Secondary endpoints included the proportion of patients with endoscopic improvement (subscores of 1 or less) from baseline to week 12. Exploratory endpoints, including clinical remission, are reported in the article, although the study was statistically powered to draw conclusions only on the primary endpoint. RESULTS: At week 12, the etrasimod 2 mg group met the primary and all secondary endpoints. Etrasimod 2 mg led to a significantly greater increase in mean improvement in modified MCS from baseline than placebo (difference from placebo, 0.99 points; 90% confidence interval, 0.30-1.68; P = .009), and etrasimod 1 mg led to an increase in mean improvement from baseline in modified MCS of 0.43 points more than placebo (90% confidence interval, reduction of 0.24 to increase of 1.11; nominal P = .15). Endoscopic improvement occurred in 41.8% of patients receiving etrasimod 2 mg vs 17.8% receiving placebo (P = .003). Most adverse events were mild to moderate. Three patients had a transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously all patients had evidence of atrioventricular block before etrasimod exposure. CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, etrasimod 2 mg was more effective than placebo in producing clinical and endoscopic improvements. Further clinical development is warranted. Clinicaltrials.gov, Number: NCT02447302.

Assessment of the real-world safety profile of vedolizumab using the United States Food and Drug Administration adverse event reporting system.

Vedolizumab is the first gut-selective integrin blocker indicated for patients with Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to examine the adverse events (AEs) profile of vedolizumab compared to anti-tumor necrosis factors (anti-TNFs) indicated for CD and UC using the FDA Adverse Event Reporting System (FAERS) database. AE reports with vedolizumab (5/20/2014-6/30/2015) and CD/UC-indicated anti-TNF drugs (adalimumab, infliximab, certolizumab pegol, and golimumab, during 8/1/1998-6/30/2015) as primary suspects were extracted from the FAERS database. AEs associated with vedolizumab were compared for signals of disproportionate reporting against anti-TNF drugs and all other drugs (1969-6/30/2015), using the proportional reporting ratio (PRR) and the empirical Bayesian geometric mean (EBGM) algorithms. The search retrieved 499 reports for vedolizumab and 119,620 reports for anti-TNFs, with 35.9% and 32.1% of these, respectively, being serious AEs. With the PRR approach, vedolizumab-associated reports had signals for 22 groups of AEs (9 were associated with serious outcomes) relative to anti-TNFs and had 34 signals relative to all other drugs. Signals detected included those reported as warnings in prescribing information and new AEs related to cardiovascular disease. Due to the voluntary nature of FAERS, this finding should be considered hypothesis generating (rather than hypothesis testing). Longer-term observational studies are required to evaluate the safety of vedolizumab.

Computer-Assisted Propofol Sedation for Esophagogastroduodenoscopy Is Effective, Efficient, and Safe.

BACKGROUND AND AIMS: Computer-assisted propofol sedation (CAPS) allows non-anesthesiologists to administer propofol for gastrointestinal procedures in relatively healthy patients. As the first US medical center to adopt CAPS technology for routine clinical use, we report our 1-year experience with CAPS for esophagogastroduodenoscopy (EGD). METHODS: Between September 2014 and August 2015, 926 outpatients underwent elective EGDs with CAPS at our center. All EGDs were performed by 1 of 17 gastroenterologists certified in the use of CAPS. Procedural success rates, procedure times, and recovery times were compared against corresponding historical controls done with midazolam and fentanyl sedation from September 2013 to August 2014. Adverse events in CAPS patients were recorded. RESULTS: The mean age of the CAPS cohort was 56.7 years (45% male); 16.2% of the EGDs were for variceal screening or Barrett's surveillance and 83.8% for symptoms. The procedural success rates were similar to that of historical controls (99.0% vs. 99.3%; p = 0.532); procedure times were also similar (6.6 vs. 7.4 min; p = 0.280), but recovery time was markedly shorter (31.7 vs. 52.4 min; p < 0.001). There were 11 (1.2%) cases of mild transient oxygen desaturation (< 90%), 15 (1.6%) cases of marked agitation due to undersedation, and 1 case of asymptomatic hypotension. In addition, there were six (0.6%) patients with more pronounced desaturation episodes that required brief (< 1 min) mask ventilation. There were no other serious adverse events. CONCLUSIONS: CAPS appears to be a safe, effective, and efficient means of providing sedation for EGD in healthy patients. Recovery times were much shorter than historical controls.