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The value of ustekinumab (UST) therapeutic drug monitoring (TDM) in clinical practice remains unclear. This study examined the impact of UST TDM on clinical decision making in patients with Crohn’s disease (CD). A total of 110 consecutive UST-treated CD patients were enrolled in this multicenter, single-arm cross-sectional study. During a single study visit, clinical decisions, disease characteristics, and serum and fecal samples were obtained. The primary outcome was congruency of the actual and two hypothetical clinical decisions based on provision of UST TDM (with and without fecal calprotectin [FCP]) to participating clinicians. Decisions were compared against those of a review panel. A sub-study retrospectively measured the associations of clinical outcomes at the next follow-up visit with serum UST concentration [UST]. No differences in the pattern of decisions by clinicians were observed before and after provision of UST TDM (P = 1.0) or UST TDM + FCP (P = 0.86). However, 39% (TDM) and 50% (TDM + FCP) of hypothetical decisions differed from the initial decisions. The review panel’s decisions differed with the addition of TDM + FCP (P = 0.0006), but not TDM alone (P = 0.16). The sub-study (n = 53) failed to detect an association between therapeutic serum [UST] at the initial study visit and clinical outcomes at the next visit. In consecutive CD patients treated with UST, the addition of TDM into routine clinical practice did not significantly impact clinical decisions and there was no association between short-term clinical outcomes and serum [UST]. Further studies are warranted before clinicians routinely implement UST TDM into clinical practice.

Background and Aims This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4β7-integrin inhibitor, and anti-tumour necrosis factor-α [anti-TNFα] agents in biologic-naïve ulcerative colitis [UC] and Crohn’s disease [CD] patients. Methods This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the USA. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness [clinical response, clinical remission, mucosal healing] and incidence rates of serious adverse events [SAEs] and serious infections [SIs]. Secondary outcomes included cumulative rates of treatment persistence [patients who did not discontinue index treatment during follow-up] and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting. Results A total of 1095 patients [604 UC, 491 CD] were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (hazard ratio [HR] = 0.42 [0.28–0.62]) and SIs (HR = 0.40 [0.19–0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence [p < 0.01] by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR = 0.58 [0.45–0.76]). Other outcomes did not significantly differ between groups. Conclusion In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile.

Background Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are complex disorders with multiple comorbidities. We conducted international patient and physician surveys to evaluate current experiences and perceptions of patients with CD or UC and physicians who treat IBD. Methods The IBD Global Assessment of Patient and Physician Unmet Need Surveys comprised a patient survey and a physician survey, fielded in North America and Europe between August 16, 2019, and November 10, 2019. Adults with CD or UC (targeted 1:1 ratio) were recruited from physicians, patient advocacy groups, and recruitment panels; physicians were recruited by recruitment agencies and panels. Results In total, 2398 patients with IBD (1368 CD, 1030 UC) and 654 physicians completed surveys. Anxiety and depression were the most common comorbidities among patients with IBD. Patients and physicians were generally aligned on treatment goals and patient-physician communication. Patients with IBD reported high quality-of-life impact by rectal urgency and need to use the toilet, which were rated as lower-impact by physicians. Patients defined remission based on symptoms; physicians defined remission based primarily on clinical tests. Patients expected current treatments to control their disease for a longer duration than did physicians. Patients expressed more concern about corticosteroid use compared with physicians; many physicians reported prescribing corticosteroids for more than 4 months per year in some patients. Conclusions Patients could benefit from education about disease remission and expectations for current therapies. High corticosteroid use is concerning to patients, and physicians should minimize the use of corticosteroids for extended periods of time.

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab for maintenance of remission in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, placebo-controlled, double-blind, phase 3 study (LAUREL) across 111 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. During open-label induction, participants received subcutaneous etrolizumab 105 mg once every 4 weeks. Participants who had clinical response at week 10 (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) proceeded into the double-blind maintenance phase and were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or matched placebo until week 62. Randomisation was stratified by baseline concomitant treatment with corticosteroids, treatment with immunosuppressants, baseline disease activity, and week 10 remission status. All participants and study site personnel were masked to treatment assignment. The primary endpoint was remission at week 62 (MCS ≤2, with individual subscores ≤1, and rectal bleeding subscore of 0) among patients with a clinical response at week 10, measured in the modified intention-to-treat population (all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02165215, and is now closed to recruitment. FINDINGS: Between Aug 12, 2014, and June 4, 2020, 658 patients were screened for eligibility and 359 were enrolled into the induction phase. 214 (60%) patients had a clinical response at week 10 and were randomly assigned to receive etrolizumab (n=108) or placebo (n=106) in the maintenance phase. 80 (74%) patients in the etrolizumab group and 42 (40%) in the placebo group completed the study through week 62. Four patients in the placebo group did not receive study treatment and were excluded from the analyses. At week 62, 32 (29·6%) of 108 patients in the etrolizumab group and 21 (20·6%) of 102 in the placebo group were in remission (adjusted treatment difference 7·7% [95% CI -4·2 to 19·2]; p=0·19). A greater proportion of patients reported one or more adverse events in the placebo group (82 [80%] of 102) than in the etrolizumab group (70 [65%] of 108); the most common adverse event in both groups was ulcerative colitis (16 [15%] patients in the etrolizumab group and 37 [36%] in the placebo group). Ten (9%) patients in the etrolizumab group and eight (8%) in the placebo group reported one or more serious adverse events. No deaths were reported in either treatment group. INTERPRETATION: No significant differences were observed between maintenance etrolizumab and placebo in the primary endpoint of remission at week 62 among patients who had a clinical response at week 10. Etrolizumab was well tolerated in this population and no new safety signals were identified. FUNDING: F Hoffmann-La Roche. ispartof: LANCET GASTROENTEROLOGY & HEPATOLOGY vol:7 issue:1 pages:28-37 ispartof: location:Netherlands status: published

Background Evidence suggests that early treatment (Tx) with biologic agents in Crohn’s disease improves long-term clinical outcomes. However, there is less evidence in ulcerative colitis (UC), and data comparing early Tx with first-line biologic vedolizumab (VDZ) to anti-tumour necrosis factor (anti-TNF) in real-world settings is needed. This study compared the clinical effectiveness and safety of UC patients who initiated VDZ or an anti-TNF as a first-line biologic within 2 years following diagnosis. Methods This was a real-world, multi-country, retrospective chart review study in Canada, Greece and the United States where biologic-naïve UC patients (≥18 years old) were treated with VDZ or an anti-TNF (adalimumab, infliximab, golimumab) agent within 2 years following diagnosis (initiated Tx May 2014–March 2018). Clinical effectiveness and safety data were collected from Tx initiation to earliest of chart abstraction date, death, or 6 months post-Tx discontinuation (Canada only). Tx persistence was defined as the duration of time from treatment initiation to discontinuation. Analyses of cumulative rates of Tx persistence, clinical response, clinical remission and mucosal healing over 24 months were estimated using Kaplan–Meier analyses. Clinical response, remission and mucosal healing were assessed using pre-defined hierarchical algorithms of standard disease measures reported in the medical records. Analyses of incidence rates (per 100 person-years [PYs]) of disease exacerbations, disease-related surgeries, serious adverse events (SAEs) and serious infections (SIs) were performed. Adjusted analyses used inverse probability weighting to balance cohorts. Results This analysis included 176 UC patients (VDZ: 86; anti-TNF: 90) from 37 sites. Mean (SD) age at index date: VDZ, 41.4 (18.9); anti-TNF, 36.8 (15.6) years (p = 0.20) and the proportion male: VDZ, 58.1%; anti-TNF, 56.7% (p = 0.84). At 12 months, 72.9% and 58.1% continued VDZ and anti-TNF respectively (p = 0.03) (Figure 1A). Though there were no differences in clinical response, clinical remission or mucosal healing between VDZ and anti-TNF groups; VDZ patients were significantly less likely to experience disease exacerbations (HR = 0.47 [95% CI: 0.32–0.69]) and SAEs (HR = 0.37 [95% CI: 0.19–0.72]) (Figure 2). Adjusted outcomes (Figures 1C and D, and 2B) were similar to unadjusted outcomes. Conclusion EVOLVE is one of the first studies that compared early VDZ Tx to early anti-TNF Tx in biologic-naïve UC patients. Results showed VDZ was associated with higher persistence, lower likelihood of experiencing disease exacerbations and a more favourable safety profile. Thus, in early UC, Tx with VDZ may improve long-term clinical outcomes. Sample size limitations warrant further study.

Infliximab is a monoclonal antibody therapy used to treat several chronic immune-mediated diseases, including Crohn’s disease, ulcerative colitis, and rheumatoid arthritis. Infliximab acts by binding to tumor necrosis factor and, thus, inhibiting the inflammatory cascade. While it is a highly effective therapy, a subset of patients on infliximab will develop a loss of response to therapy. In these circumstances, therapeutic drug monitoring of infliximab offers a rational approach to clinical decision making and is associated with improved outcomes. While infliximab has most commonly been measured by immunometric approaches, mass spectrometric approaches offer the opportunity to improve test accuracy and reduce test costs. Herein, we describe a simple, bottom-up high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) approach for quantitation of infliximab in serum. Method development included pre-digestion and digestion experiments to determine critical sample preparation steps, optimization of the workflow and selection of rapidly produced proteolytic peptide(s) for quantitation. The workflow was further improved by automating all sample preparation steps on a robotic liquid handler, facilitating implementation in routine clinical use. A method comparison was performed against a Health Canada and US Food and Drug Administration licensed enzyme-linked immunosorbent assay. Our LC–MS/MS assay accurately reported concentrations based on drug manufacturer targets and demonstrated no interference from endogenous antibodies to infliximab; immunoassay methods did not share these performance characteristics. This LC–MS/MS method provides a workflow amenable to implementation in a clinical laboratory and desired performance characteristics for guiding clinical decision making.

The use of immunosuppressive therapies for immune-mediated disease (IMD) is associated with an elevated risk of infections and related comorbidities. While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal, due in part to uncertainty about their efficacy or safety under these clinical situations. To address this concern, a multidisciplinary group of Canadian physicians with expertise in dermatology, gastroenterology, infectious diseases and rheumatology developed evidence-based clinical guidelines on vaccinations featuring 13 statements that are aimed at reducing the risk of preventable infections in individuals exposed to immunosuppressive agents.

Background Fecal calprotectin (FC) is a stool biomarker that has been shown to be sensitive and specific for mucosal inflammation in patients with inflammatory bowel disease (IBD). The test is limited by the requirement for patients to collect and return stool samples. A home-based FC test may improve test adherence. The aim of this study is to evaluate the usability of the IBDoc, a home-based FC measuring test, and to determine the accuracy of results compared with traditional lab-based ELISA values. Methods Patients were prospectively enrolled from 3 tertiary sites across Canada between May and August 2017. Patients completed a questionnaire establishing ease-of-use of the IBDoc. Patients completed a FC measurement using the IBDoc, and results were compared with an ELISA-determined FC measurement on the same stool sample. Results Sixty-one participants were enrolled in the study (29 CD, 32 UC). Seventy-nine percent of patients (48 of 61) agreed that the IBDoc was easy to use, with 85% (52 of 61) of patients strongly agreeing that they were willing use the home kit in the future. The IBDoc and ELISA measurement comparison showed an 88% agreement across all values. There were no false positives or negatives using qualitative comparison. Conclusions The home-based IBDoc FC measuring test is acceptable to patients and correlates extremely well with the standard ELISA-determined FC value. The IBDoc enables clinicians to more easily adopt a treat-to-target approach, improve long-term outcomes, and patients' quality of life with IBD. This study is registered at ClinicalTrials.gov, number NCT03408249.

Background Gastroenterologists should accurately describe endoscopic findings and integrate them into management plans. We aimed to determine if trainees and staff are describing inflammatory bowel disease (IBD) lesions in a similar manner. Methods Using 20 ileocolonoscopy images, participants described IBD inflammatory burden based on physician severity rating, and Mayo endoscopic score (MES) (ulcerative colitis [UC]) or simple endoscopic score (SES-CD) (Crohn’s disease [CD]). Images were selected based on agreement by three IBD experts. Findings of varying severity were presented; 10 images included a question about management. We examined inter-observer agreement among trainees and staff, compared trainees to staff, and determined accuracy of response comparing both groups to IBD experts. Results One hundred and twenty-nine staff and 47 trainees participated from across Canada. There was moderate inter-rater agreement using physician severity rating (κ = 0.53 UC and 0.52 CD for staff, κ = 0.51 UC and 0.43 CD for trainees). There was moderate inter-rater agreement for MES for staff and trainees (κ = 0.49 and 0.48, respectively), but fair agreement for SES-CD (κ = 0.37 and 0.32, respectively). For accuracy of response, the mean score was 68.7% for staff and 63.7% for trainees (P = 0.028). Both groups identified healed bowel or severe disease better than mild/moderate (P < 0.05). There was high accuracy for management, but staff scored higher than trainees for UC (P < 0.01). Conclusion Inter-rater agreement on description of IBD lesions was moderate at best. Staff and trainees more accurately describe healed and severe disease, and better describe lesions in UC than CD.

Background For patients with UC, flexible maintenance dosing therapy may confer advantages for safety, efficacy, costs and patient preference. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Aim To assess the efficacy and safety of tofacitinib dose de-escalation and escalation in patients with UC. Methods We evaluated data (November 2017 data cut-off) from OCTAVE Open, an ongoing, open-label, long-term extension study. The dose de-escalation group comprised 66 tofacitinib induction responders in remission following 52 weeks' tofacitinib 10 mg b.d. maintenance therapy, subsequently de-escalated to 5 mg b.d. in OCTAVE Open. The dose escalation group comprised 57 tofacitinib induction responders who experienced treatment failure while receiving 5 mg b.d. maintenance therapy, subsequently escalated to 10 mg b.d. in OCTAVE Open. Results After tofacitinib de-escalation, 92.4% (61/66) and 84.1% (53/63) of patients maintained clinical response and 80.3% (53/66) and 74.6% (47/63) maintained remission, at months 2 and 12, respectively. After dose escalation, 57.9% (33/57) and 64.9% (37/57) of patients recaptured clinical response and 35.1% (20/57) and 49.1% (28/57) were in remission, at months 2 and 12, respectively. The incidence rate of herpes zoster with dose escalation (7.6 patients with events/100 patient-years) was numerically higher than in the overall tofacitinib UC programme. Conclusions Following tofacitinib de-escalation in patients already in remission on 10 mg b.d., most maintained remission, although 25.4% lost remission, at month 12. For induction responders who dose-escalated following treatment failure on 5 mg b.d. maintenance therapy, 49.1% achieved remission by month 12. (ClinicalTrials.gov number: NCT01470612).

Background In patients with ulcerative colitis (UC), fecal calprotectin (FC) concentrations correlate with endoscopic inflammation evidence. This study investigated the effect of vedolizumab induction on FC concentrations and whether FC concentrations could be a reliable surrogate measure of disease status. Methods Data from the placebo-controlled, phase 3 trial GEMINI 1 were used to evaluate week-6 relationships between outcomes (including clinical remission, mucosal healing [MH], and endoscopic remission) and both absolute FC concentration values and relative FC concentration changes from baseline (%FC0-6). Sensitivity and specificity were calculated by cross-tabulation; the value of week-6 FC concentration as surrogate biomarker was measured with Youden J statistic computed for various cut points. Results GEMINI 1 induction phase enrolled 895 patients. Fecal calprotectin concentration decreases were deeper in patients with clinical remission, MH, and/or endoscopic remission than in patients without. The best week-6 indicator of clinical or endoscopic remission in this data set was absolute FC concentration ≤150 µg/g. The surrogate biomarker values (based on areas under the curve) for the best-performing cut points (FC0-6 reduction >90%, FC ≤150 µg/g) were fair (range, 0.70–0.77, total population). More patients met the ≤150 µg/g cut point with vedolizumab than with placebo. Baseline FC concentrations were not correlated with clinical outcomes. Conclusions Fecal calprotectin concentration reductions were greater with vedolizumab induction than with placebo. Week-6 FC concentrations had only fair surrogate biomarker value for endoscopic status. Our data suggest that, while FC may reflect inflammatory burden, FC concentration after vedolizumab induction may not be a robust biomarker of mucosal inflammation.

Background and Aims Patients with inflammatory bowel disease (IBD) have higher incidence of psychosocial disorders, including depression. As suicide is the most severe manifestation of depression, we sought to identify if patients with IBD have a higher incidence of suicide through a systematic review and meta-analysis. Methods Systematic literature searches for articles using EMBASE and MEDLINE using Ovid were conducted to identify studies investigating suicide in IBD. Reference harvesting of the bibliographies of key articles was also performed. We included studies reporting expected number of death or standardized mortality ratio (SMR) for suicide in IBD. Meta-analysis for each IBD condition (Crohn’s disease [CD] and ulcerative colitis [UC]) was conducted separately, as well as combined. Results Seven cohort studies were identified through our search strategy and included in our systematic review and meta-analysis. In our analysis, the SMR for suicide in patients with IBD for all studies included was 1.20 (95% CI, 0.94–1.54). The overall pooled SMR for CD and UC were 1.36 (95% CI, 0.98–1.88) and 1.16 (95% CI, 0.8–1.69) respectively. Conclusions Patients with Crohn’s disease and ulcerative colitis may have an increased risk of suicide. These results highlight the importance physicians must place on ensuring the mental health of patients with IBD is both assessed and treated appropriately.

Background Corticosteroid is an effective therapeutic option for inflammatory bowel disease flares, but its adverse effects may compromise treatment adherence and reduce patients' quality of life. There is lack of data on the incidence of corticosteroid-induced mood changes in this patient population, which may be underappreciated by healthcare providers in clinical practice and interfere with optimal care. This study aimed to determine the rate of mood changes in this patient population. Methods In this prospective observational study, adult outpatients treated with prednisone for inflammatory bowel disease flares were considered for inclusion. Participants completed validated questionnaires (Beck Depression Inventory-II and Activation Subscale of Internal State Scale version two) before starting prednisone, after two weeks of prednisone, and at the end of prednisone taper to assess for mood changes. Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index were used to monitor clinical disease activity. Results Fifty-three subjects were included in the analyses. The rate of mood change after two weeks of prednisone was 49.1%, primarily driven by increase in mood towards (hypo)mania. Younger age was an independent risk factor. Mood state returned to pretreatment level at the end of treatment. There was no correlation between clinical disease activity change and mood change. Conclusions Oral prednisone for inflammatory bowel disease flare is associated with high rate of mood change. As prednisone is a critical part of induction therapy, ways to minimize this adverse event must be studied. For now, healthcare providers should inform patients and monitor closely for this adverse event.

Background The efficacy of golimumab to induce and maintain remission in biologic-naïve patients with ulcerative colitis (UC) is established from placebo-controlled trials. However, golimumab’s real-world effectiveness, important to physicians and payers, remains unexplored. Aim The goal of this study was to describe real-world use and rate of persistence among UC patients with golimumab therapy and to assess factors that predict discontinuation during golimumab maintenance treatment. Methods A retrospective study of UC patients receiving golimumab maintenance therapy (August 2012–August 2015) was conducted on dosing data from a national case management program. Treatment persistence, defined as time from index prescription to the last dose (gap in dose >60 days), was assessed using Kaplan-Meier survival analysis. Predictors of treatment persistence were explored with Cox proportional hazards regression. Results One hundred thirty-six patients (50.7% male) with a mean (SD) age of 44.4 (15.6) years were included. At golimumab initiation, 72.1% were naïve to anti-TNFs; 77.2% received 200 mg, while 4.4% and 18.4% received 50 mg and 100 mg, respectively, every 4 weeks (induction therapy). The median time to discontinuation was 530 days, with a cumulative probability of 63% to remain on therapy at one year. Age, gender, golimumab induction, golimumab maintenance dose and prior anti-TNF exposure were not significantly associated with treatment persistence. Dose adjustment occurred in 7.4% of patients during maintenance treatment. Conclusions Overall, the persistence rate of golimumab observed in the current real-world study is similar to that described in previous single-centre UC cohorts and consistent with that seen in controlled clinical trials.

Background Deep ulcers have been described as a marker of severe disease phenotype in patients with IBD and play a role in choice or escalation of therapy. However, there is no agreed upon characterization of deep ulcers in the literature. We therefore assessed Canadian gastroenterologists’ ability to identify the presence of deep ulcers on endoscopic images. Methods We present a post-hoc analysis of a cross-sectional questionnaire from gastroenterologists across Canada (March-October 2017). Three IBD experts independently rated 20 ileocolonoscopy images of single bowel segments. They described the images by selecting descriptors from a list developed a priori. Images described by all 3 experts as having “deep ulcers” were retained for analysis (5 images). Survey participants similarly applied descriptors from the same list to each endoscopy image. We examined the percent agreement between the gastroenterologists and the experts. The percent agreement for each question was summarized using median and IQR. Difference in median scores in physician subgroups was determined using the Mann-Whitney U test. We also assessed the inter-observer agreement on the presence of deep ulcers amongst gastroenterologists using Fleiss Kappa. Results 131 gastroenterologists participated in the study. The majority (55.7%) were between 36–50 years old. 48% were in practice for less than 10 years. 59.5% practiced in an academic setting. 9.9% of responders were pediatric gastroenterologists. The median agreement between the gastroenterologists and the experts was 30.5% (30.5–76.3), indicating an under-recognition of deep ulcers. As a group, inter-observer agreement on the presence of deep ulcers was minimal (k = 0.39, CI: 0.16–0.65). Inter-observer agreement was lower in the academic setting than the community setting (k= 0.39 vs k= 0.49 respectively) and was fairly similar in those with more experience compared to those with less experience (k= 0.40 for less than 10 years in practice, vs k= 0.36 for those with greater than 10 years in practice). Compared to the experts’ responses, there was no significant difference if the physician practiced in an academic vs community setting (49.24% correct identification vs 54.52%, p = 0.6004) or if the physician had less than 10 years’ experience vs greater than 10 years’ experience (48.26% vs 53.44%, p =0.2948). Conclusion Deep ulcers have been described as a critical indicator of disease severity in patients with IBD. However, our study shows that there is poor agreement between physicians in identifying this important feature. This indicates the need for a standardized definition of deep ulcers to prevent undertreatment of patients who require escalated therapy.

Background Previously, we identified subsets of biologic-naïve patients (pts) with Crohn’s disease (CD) from the EVOLVE study who had higher rates of clinical remission (CR) [Fig 1] when initiating vedolizumab (VDZ) vs anti-TNFα treatment, using prediction models based on multiple baseline characteristics.1,2 To aid use in practice, we investigated whether these subsets could be identified using simpler rules based on fewer baseline characteristics. Methods Using data from EVOLVE, we used recursive partitioning and regression tree (RPART) classification to predict membership in the previously identified higher CR subsets for VDZ. The RPART algorithm repeatedly splits data, based on baseline predictors (demographics, prior treatments, clinical characteristics at treatment initiation, Charlson comorbidity index, prior extraintestinal manifestations [EIMs], and prior healthcare resource use). At each split, the predictor and its value as chosen by the algorithm to split the data were those that maximized the number of pts classified correctly. Simplified rules were developed from the resulting RPART decision trees. Analyses of the treatment effect of VDZ vs anti-TNFα were conducted in the subsets of pts identified by each rule. Results Pts with data on CR and candidate predictors were included (VDZ [n=195]; anti-TNFα [n=245]). Three simplified rules (A, B, & C) were identified (Table 1). Pt characteristics included in the rules (exacerbation ongoing at treatment initiation, no emergency department/emergency room (ED/ER) visits prior to treatment initiation, no fistulae at most recent assessment prior to treatment initiation, pre-initiation disease behaviour) were among the main predictors of CR in VDZ pts identified previously. Pts identified by Rule A comprised 32% of the EVOLVE population, and were those who 1) had an exacerbation ongoing at index, 2) did not have ED/ER visits prior to initiation and 3) had pre-initiation disease behaviour classified as other than stricturing with/without perianal disease. Among these pts, median time to CR for VDZ and anti-TNFα pts were 6.7 and 18.1 months, respectively (unadjusted log-rank p Conclusion Simple rules were developed to identify biologic-naïve, CD pts in whom VDZ initiation appeared to have a larger effect on CR relative to anti-TNFα initiation. Validation of these rules in other data sources is important to confirm these findings; if validated, these simplified rules can inform targeting of treatment and optimization of outcomes for pts with CD treated with VDZ.

Background Innate immune defects play a role in the pathogenesis of CD. Enhancing innate immune competency and restoring mucosal barrier function provide a novel approach to treat CD. QBECO SSI is a first-in-class immunotherapy designed to correct innate immune dysfunction underlying CD. This analysis is from subjects in the open label portion of a planned controlled trial. Objectives were to assess endoscopic response at Wks 16 and 26, and select the optimal induction timepoint for the RCT. Safety and treatment compliance were also evaluated. Methods 20 pts with moderate-to-severe CD were enrolled and received QBECO SSI by sc injection every other day for up to 52 wks. Minimum eligibility: Simple Endoscopic Score for CD (SES-CD) ≥7 (ileitis ≥4), abdominal pain (AP) score >21 (11-point scale) or liquid/very soft stools (SF) (BFS Type 6 or 7) >10 for 7 consecutive days during screening. Pts were evaluated for clinical symptoms and endoscopy at Wks 16, 26, and 52. After evaluation at the induction period (Wk 26) pts could continue in maintenance up to Wk 52. Endoscopies were evaluated by central blinded read and pts reported daily symptoms. Endoscopic response defined as ≥50% reduction in SES-CD from baseline. Clinical remission defined as AP and SF ≤21. Results Mean age was 43.6 (SD 13.6) yrs; 60% men and 60% previously treated with biologics. Mean yrs since CD diagnosis was 14.4 (10.1), AP score 30.4 (15.8), SF score 36.2 (19.1) and mean SES-CD at baseline was 12.5 (6.7) indicating a more difficult to treat population. Endoscopic response rate by central read during the induction period was 30% (6/20) overall, 38% (3/8) for biologic naïve and 25% (3/12) biologic experienced pts (ITT analysis). Similar number of pts achieved endoscopic response at Wk 16 (4 pts) as 26 (3 pts). Mean SES-CD improved through Wk 26 with a 0.6 point greater reduction at Wk 26 compared to 16. Change in SES-CD from baseline in biologic naïve pts was -2.9 (5.8) at Wk 16 and -4.1 (6.7) at 26. Clinical remission was achieved by 45% (9/20) of pts at Wk 16 and 40% (8/20) at Wk 26; 16 pts continued into the maintenance phase of the study. By central evaluation, 13% (2/16) were in endoscopic response at Wk 52. QBECO SSI was very well tolerated. 8/20 (40%) pts reported AEs related to treatment. Most frequency reported related AE was injection site erythema (2/20, 10% pts). Majority of AEs were mild and no other related AE was reported by more than 1 patient. Conclusion Week 26 was the optimal endoscopic evaluation timepoint for QBECO SSI treatment and will be utilized in the larger RCT. Both biologics naïve and experienced patients showed response to QBECO SSI treatment by Weeks 26 and 52, with higher response rates in biologics naïve patients. QBECO SSI was well tolerated.

Background With the COVID-19 pandemic, the demand and availability of telehealth in outpatient care has increased. Although use of telehealth has been studied and validated for various medical specialties, relatively few studies have looked at its role in gastroenterology despite burden of chronic diseases such as inflammatory bowel disease (IBD). Aims To assess effectiveness of telehealth medicine in gastroenterology by comparing medication adherence rate for patients seen with telehealth and traditional in-person appointment for various GI conditions. Methods Retrospective chart analysis of patients seen in outpatient gastroenterology clinic was performed to identify patients who were given prescription to fill either through telehealth or in-person appointment. By using provincial pharmacy database, we determined the prescription fill rate. Results A total of 241 patients were identified who were provided prescriptions during visit with their gastroenterologists. 128 patients were seen through in-person visit during pre-pandemic period. 113 patients were seen through telehealth appointment during COVID pandemic. The mean age of patients in telehealth cohort was 42 years (57% male). On average patients had 10 prior visits with their gastroenterologists before index appointment, used for adherence assessment. 92% of patients were seen in follow-up, while 8% were seen in initial consultation. The majority of the patients in the telehealth cohort had IBD (89%), while the remaining 11% had various diagnoses, including functional GI disorder, gastroesophageal reflux disease, viral hepatitis, or hepatobiliary disorders. Biologic therapy was the most commonly prescribed medication (66.4%). 45 patients were provided either new medication or dose change, and 68 patients had prescription refill to continue their current medications. It took a mean of 18 days (SD = 16.2) for patients to fill their prescriptions. Prescription fill rate for patients seen through telehealth and in-person visit were 98.2% and 89.1% (P = 0.004) respectively. Patients seen through telehealth were 6.8 times more likely to fill their prescriptions compared to the in-person counterparts (OR 6.82, CI 1.51 – 30.68, P = 0.004). When we compared adherence rate while excluding biologic therapies, the prescription fill rate was 94.7% in telehealth group and 81.4% in in-person group (OR 4.11, CI 0.88 – 19.27, P = 0.056). Due to high level of adherence, statistical analysis comparing adherent and non-adherent groups was performed but yielded insignificant results. Conclusions Medication adherence rate for patients seen through telehealth was higher compared to patients seen through in-patient visit in this study. Telehealth is a viable alternative for outpatient care especially for patients with chronic GI conditions such as IBD. Funding Agencies None

Background Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC) is characterized by pancolitis with rectal sparing and is associated with an increased risk of colorectal and biliary malignancies. Currently, pharmacologic management of IBD in the setting of PSC is the same as in IBD alone. Aims To assess patterns in medical therapy, and incidence of adverse outcomes in patients with concomitant IBD and PSC. Methods A retrospective review was conducted on all PSC-IBD patients followed between January 2010 and June 2018. The Endoscopic Mayo Score was used to grade IBD severity in PSC-ulcerative colitis (UC). Results 69 patients were identified, 44 (63.8%) were male. The mean ages of IBD and PSC diagnosis were 28.6 (SD 14.9) and 37.0 (SD 18.9) years, respectively. The median length of follow up was 12 (range 2–49) years. 52 (75.4%) patients had UC, and 17 (24.6%) had Crohn’s disease (CD). 28 (87.5%) PSC-UC patients had pancolitis, and 4 (12.5 %) had proctitis. Among those with pancolitis, 8 (28.6%) had relative rectal sparing. 4 (14.3%) patients had more severe inflammation proximally, whereas only 1 (3.6%) had more severe distal inflammation. 23 (82.1%) patients had the same degree of inflammation throughout. 14 (93.3%) PSC-CD patients had colitis/ileocolitis and 1 (6.7%) had ileitis. Among those with PSC-UC, 16 (50.0%), 12 (37.5%), and 4 (12.5%) patients had grade 1, 2, and 3 disease, respectively. 62 (89.9%) PSC-IBD patients were treated with aminosalicylates, and 26 (37.7%) with biologics at some point in their IBD course. 26 (37.7%) were treated with aminosalicylates alone. 4 (5.8%) did not require any IBD therapy. Cholangiocarcinoma, colorectal cancer, and gallbladder cancer developed in 8 (11.6%), 1 (1.4%), and 1 (1.4%) PSC-IBD patients, respectively. 16 (23.2%) patients required partial or total colectomy. Indication for surgery was inflammation or stenosis, dysplasia, and neoplasia in 13 (81.3%), 2 (12.5%), and 1 (6.3%) patients, respectively. Conclusions The majority of this cohort had UC with mild disease activity. Pancolitis was common, with frequent rectal sparing and more severe right-sided inflammation. Despite the predominance of low-grade colitis, a large portion of patients required treatment with biologics. The incidence of adverse outcomes underscores the need for strict adherence to recommended surveillance practices. Low grade endoscopic activity, typical of the quiescent IBD course in PSC-IBD, may mask low grade histologic inflammation, which in turn may contribute to the increased risk of colonic neoplasia. Further studies are needed to determine the best management strategy for IBD in patients with PSC. Funding Agencies None

BACKGROUND Half of patients with inflammatory bowel disease (IBD) require hospitalization. We sought to characterize inpatient quality indicators of care and outcomes during IBD-related hospitalizations at 4 major IBD referral centers in Canada. METHODS We conducted a multicenter retrospective cohort study of patients with IBD admitted from 2011 to 2013 to tertiary centers in Toronto, Montreal, Ottawa, and Vancouver. We assessed the following inpatient indicators of care: pharmacological venous thromboembolism (VTE) prophylaxis, Clostridium difficile testing, and medical rescue therapy for steroid-refractory ulcerative colitis (UC). We also evaluated rates of VTE, C. difficile infection, and IBD-related surgery. RESULTS There were 837 patients hospitalized for IBD (Crohn's disease, 59%; UC, 41%). The proportion of patients with IBD who received VTE prophylaxis and C. difficile testing were 77% and 82%, respectively, although these indicators varied significantly by center and admitting specialty. Patients admitted under surgeons were more likely than those admitted under gastroenterologists to receive VTE prophylaxis (84% versus 74%, P = 0.016) but less likely to be tested for C. difficile (41% versus 88%, P < 0.0001). The rate of VTE was the same for those who did and did not receive VTE prophylaxis (2.2 per 1000 hospital-days). Among the 14 VTE events, 79% had received prophylaxis, but only 36% within 24 hours of admission. Among steroid-refractory UC patients, 70% received rescue therapy within 7 days of steroid initiation. The proportion of patients with UC and CD who required respective bowel surgery was 18% and 20%, respectively. CONCLUSIONS There are opportunities to optimize quality of care among hospitalized patients with IBD.

Background A primary goal in IBD management is achieving disease remission; however, patient (pt)-physician alignment on this goal is unclear. International online surveys were conducted to gain insights into pts’ and physicians’ perspectives on real-world management of IBD. Herein, we report survey findings pertaining to their understanding and perceptions of disease remission in IBD. Methods Surveys were completed online by pts and physicians in Canada, France, Germany, Italy, Spain, UK, and US. Using a mixed-recruitment method, pts were identified by physicians, pt advocacy groups, and panels, while physicians were identified by recruitment agencies and panels. Eligible pts were aged ≥18 y who were diagnosed with and received treatment for Crohn’s disease (CD) or ulcerative colitis (UC) and had not undergone surgery for UC. Eligible physicians were gastroenterologists who had treated pts with CD or UC (≥12 each) in the last month, were responsible for treatment decisions of their IBD pts, and for whom ≥30% of their IBD pts had moderate or severe disease per prespecified clinical criteria. A 1:1 CD:UC ratio was targeted for the pt survey. Alignment between pts and physicians on remission definitions and pt-physician communication about remission was assessed. Physicians’ estimates of remission rates in their moderate/severe IBD pts receiving biologic therapy and their satisfaction (1=very dissatisfied to 7=very satisfied) with remission rates with current IBD treatments also were reported. Results A total of 2398 IBD pts (1368 CD [40% male], 1030 UC [45% male]) and 654 physicians completed the surveys. Mean pt age was 42 y (CD) and 44 y (UC). Physicians had mean monthly caseloads of 42.9 (CD) and 43.3 (UC). The most common primary care settings were university/teaching hospitals (41%), private practices (31%), and regional/community hospitals (20%). Nearly one quarter of pts reported never having discussed remission with their physician; only 7% of physicians reported that they typically did not discuss remission with their pts. Pts most commonly defined remission as symptom resolution (45%), whereas most physicians defined remission through test results (64% CD, 70% UC), including colonoscopies (56% CD, 58% UC), biopsies (36%, 37%), and biochemical tests (8%, 6%). Most pts (62% CD, 64% UC) had never heard of the term “mucosal healing.” Despite low physician-reported remission rates (CD: 37%–54%; UC: 37%–55%), 25% and 36% of physicians reported high satisfaction (score ≥6) with CD and UC remission rates, respectively. Conclusions This international survey demonstrated differences in pts’ and physicians’ definitions of IBD remission and in their understanding of the role of histologic remission in IBD. The findings highlight the need for improved pt-physician communication and education regarding remission, which may improve adherence and outcomes.

Background There is little long-term research (≥12 months) in ulcerative colitis (UC) and Crohn’s disease (CD) patients investigating the impact on clinical effectiveness of combined (combo) therapy of vedolizumab (VDZ) plus immunomodulators/immunosuppressants (IMMs) compared with VDZ monotherapy. Research suggests the use of concomitant aminosalicylates [5-ASAs] in UC may not bolster effectiveness. Finally, it is unclear if the safety profile differs between VDZ monotherapy and combo therapy. This study described clinical effectiveness and safety outcomes in patients with UC or CD treated with first-line biologic VDZ as monotherapy or combo therapy with IMMs or 5-ASAs (UC only). Methods This was a real-world, multi-country (Canada, Greece and the USA), retrospective chart review study of biologic-naïve UC and CD patients (≥18 years old) treated with VDZ (initiated Tx May 2014–March 2018). Data were collected from Tx initiation to the earliest of death and chart abstraction date. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan-Meier method with unadjusted comparisons conducted using the log-rank test. Clinical response and remission were assessed from standard disease measures reported in medical records. Analyses of unadjusted incidence rates (per 100 person-years [PYs]) of disease exacerbations, disease-related surgeries, serious adverse events (SAEs) and serious infections (SIs) were performed. For these analyses in monotherapy vs. VDZ+IMMs, UC and CD patients were combined due to restrictions of sample size and a number of events. Results This analysis included 318 patients treated with VDZ (monotherapy: UC = 53, CD = 108; VDZ+IMMs: UC = 22, CD = 24; VDZ+5-ASAs: UC = 111). There were no observed differences in age, sex or disease duration between patients on monotherapy vs. VDZ+IMMs or vs. VDZ+5-ASAs. Data trends in effectiveness outcomes were similar in monotherapy vs. VDZ+IMMs over 24 months (Figure 1). Tx persistence (monotherapy: 71.6%; VDZ+5-ASAs: 82.7%; p = 0.40), clinical remission (monotherapy: 54.3%; VDZ+5-ASAs: 87.7%; p = 0.37) and clinical response (monotherapy: 81.7%; VDZ+5-ASAs: 92.2%; p = 0.54) were also similar between monotherapy and VDZ+5-ASAs over 24 months. Safety outcomes were similar between groups (Figure 2). Conclusion Though sample sizes were small, the unadjusted trends in the results of this long-term real-world study suggest that biologic-naïve UC or CD patients treated with VDZ alone may have similar clinical effectiveness outcomes to patients receiving VDZ+IMMs. Trends in data also suggest that in patients with UC, VDZ+5-ASAs may not be more effective than VDZ alone.

Background Corticosteroids are a mainstay of inflammatory bowel disease (IBD) treatment but are not as effective as maintenance therapy and prolonged exposure is associated with significant morbidities. We assessed real-world management of IBD using an international online survey of patients (patients) and physicians and present results related to steroid use for IBD. Methods The online survey was conducted in Canada, France, Germany, Italy, Spain, UK, and the USA. The mixed-recruitment methodology was used: patients were recruited by physicians, pt advocacy groups, and panels; physicians were recruited by recruitment agencies and panels. Eligible patients were adults with Crohn’s disease (CD) or ulcerative colitis (UC) (targeted 1:1 ratio CD:UC) who had received IBD treatment but had not had surgery for UC. Eligible physicians were gastroenterologists who had treated ≥12 CD patients and ≥12 UC patients (≤70% with a disease of mild severity) in the prior month and were responsible for treatment decisions. Results Surveys were completed by 2398 IBD patients (1368 CD, 1030 UC) and 654 physicians. Mean ages were 43 y and 45 y for patients with CD and UC, respectively; 60% and 55% were female. Most patients (93% CD, 78% UC) had moderate/severe IBD per clinical criteria; 71% and 47%, respectively, had ever required hospitalisation. Physicians had a mean monthly caseload of 42.9 CD patients and 43.3 UC patients, and 62.4%–67.2% of their IBD patients had moderate/severe disease. Biologic therapy was currently used by 50% of CD patients and 32% of UC patients, consistent with results for physicians (54% CD, 43% UC). Most patients (69% CD, 58% UC) reported a loss of response (LOR) to prior treatments, and most physicians reported that their patients experienced a LOR to biologic therapy fairly/very frequently (66% CD, 56% UC). Approximately 75% of IBD patients had ever used steroids for their IBD; steroid use of ≥4 or ≥6 months in the past year was reported by 35% and 18% of CD patients, respectively, and by 40% and 19% of UC patients. Physicians reported that 40% and 14% of their IBD patients used steroids for ≥4 or ≥6 months in the past year. Among patients currently receiving steroid therapy, many (48% CD, 42% UC) were concerned about any steroid use, and two-thirds reported wanting to stop steroid treatment as soon as the disease was under control. Only 27% of physicians reported a concern about any steroid use; approximately half reported a concern about ≥4 months of steroid use per year. Conclusion This international survey demonstrated that steroid use is prevalent and LOR to biologics is common among moderate/severe IBD patients. There were differences in pt and physician perception of steroid use; many physicians believed ≥4 months of steroid use per year was not a concern. A significant unmet need remains for treatments that provide sustained control of IBD.

Background Crohn’s disease (CD) can lead to complications that impact treatment (Tx) decisions and its clinical effectiveness. The objective of this analysis was to compare clinical effectiveness outcomes of CD patients treated with first-line biologic vedolizumab (VDZ) who did not have a complicated disease phenotype (non-complicated) to VDZ patients who had complications (complex disease). Methods This was a retrospective real-world cohort study of biologic-naïve CD patients (≥18 years old) in Canada, Greece and the USA who initiated VDZ Tx between May 2014 and March 2018. Data were collected from Tx initiation to the earliest of chart abstraction date or death. The non-complicated CD was defined as patients who had mild or moderate disease severity and no active fistula at Tx initiation, had no prior CD-related surgeries since diagnosis and no CD-related hospitalisations within 12 months prior to Tx initiation. The complex disease cohort encompassed all other CD patients. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan–Meier method. Using pre-defined hierarchical algorithms, clinical response and clinical remission were assessed from standard disease measures reported in the medical records. Results This analysis included 218 CD patients treated with VDZ (non-complicated: 64 (29.3%); complex: 154 (70.6%) from 37 sites. Mean (SD) age at Tx initiation: non-complicated, 46.2 (15.8); complex, 54.0 (16.7); male: non-complicated, 45.3%; complex, 55.2%. Cumulative rates of clinical response were significantly greater in non-complicated than complex disease patients over 24 months (non-complicated: 93.0%, complex: 76.0%, p < 0.01) (Figure 1). Tx persistence (non-complicated: 76.7%, complex: 66.6%, p = 0.68) (Figure 2) and clinical remission (non-complicated: 81.9%, complex: 73.5%, p = 0.36) (Figure 1) were not significantly different between the two cohorts over 24 months. Fewer patients had data for mucosal healing over 24 months, and it was also not significantly different between groups at 12 months (non-complicated: 66.4%, complex: 60.2%, p = 0.95). Conclusion A high proportion of patients (70%) had a complex disease when VDZ Tx was initiated but those with non-complicated phenotype had a higher response rate. To help guide physicians in positioning the optimal Tx for biologic-naïve CD patients, it is important to identify the sub-group of patients who can most benefit from VDZ Tx. The results of this real-world study suggest that the biologic-naïve, non-complicated CD patients benefit more from VDZ treatment compared with those with disease complications.

Background Therapeutic drug monitoring is an important adjunct in optimising IBD management in patients treated with anti-TNF therapies. However, it remains unclear whether these principles apply to non-anti-TNF biologic therapies, such as the anti-IL12/23 agent, ustekinumab (UST). A follow-up analysis of the ‘mUST-DECIDE’ study explores the correlation between UST drug level and clinical outcomes. Methods 111 consecutive UST-treated adult CD patients across 11 sites in Canada from April 2017 to January 2018 were evaluated. Clinical decisions were recorded for all subjects at the single study visit and blood was drawn for TDM (Sanquin, radioimmunoassay). A retrospective chart review was completed in patients who had a follow-up visit ≥ 30 days after the baseline visit. Improved disease control (primary outcome) was defined as a composite assessment outcome meeting ≥ 1 disease control criterion (symptomatic, endoscopic/imaging, biochemical) without any of the non-response criteria (inadequate or loss of response, worsening of any disease control criteria, initiation of any CD-related medications and adverse events). Serum [UST] were categorised as therapeutic, subtherapeutic or uninterpretable based on their position in a 2 compartment PK model [subjects on Q8W dosing were assessed as per the log-linear model which projected a therapeutic level of ≥4.5 µg/ml at 4 weeks and ≥1.0 µg/ml at 8 weeks]. Results 53 patients had a clinical follow-up visit and an interpretable serum [UST]. Patients had refractory disease (89% anti-TNF-exposed, median 16.4 years since diagnosis), but clinically well (66% had baseline HBI Conclusion The sub-study did not detect any association between routine serum [UST] and short-term clinical outcomes at the next patient visit. These data broadly suggests that the routine measurement of serum UST in CD patients does not aid in disease management, though further studies across different clinical scenarios (e.g. loss of response) are warranted.

Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of UC. Safety and efficacy of tofacitinib were demonstrated in Phase (P)2/3 induction studies, a 52-week, P3 maintenance study, and are being further investigated in an ongoing, open-label, long-term extension (OLE) study.1,2 Here, we provide an updated analysis of age as a risk factor for adverse events (AEs) in the tofacitinib UC clinical programme.3 Methods Proportions of AEs and serious AEs (SAEs), and incidence rates (IRs; unique patients with events per 100 patient-years) for AEs of special interest (AESIs), were determined for two cohorts: the Maintenance Cohort (patients who received placebo or tofacitinib 5 or 10 mg twice daily [BID] in the maintenance study) and the Overall Cohort (all tofacitinib 5 or 10 mg BID-treated patients in the P2/P3/OLE studies; as of May 2019), stratified by age. Multivariable Cox proportional hazards regression analyses were performed to assess whether older age was associated with increased risk of AESIs in the Overall Cohort. Results In the Maintenance Cohort, IRs of AEs and SAEs were generally similar between treatment groups, with no age-related trend in the proportions of AEs in tofacitinib-treated patients. AESIs were infrequent in both treatment groups; however, herpes zoster (HZ; non-serious and serious) IRs were numerically higher in the ≥40 to Conclusion In the Overall Cohort, there was a trend for an increase in the rates of OIs, HZ, malignancy (excl. NMSC) and NMSC with increasing age. In multivariate analyses, older age was associated with increased risk of malignancy (excl. NMSC), NMSC and HZ. The results of this analysis are generally consistent with previous studies suggesting older age may be associated with an increased risk of certain AESIs in patients with UC, and in some instances in the general population.4 References

Randomized controlled trials (RCTs) have demonstrated that therapies targeting tumor necrosis factor (TNF) and α₄β₇ integrin are effective when given as monotherapy in inducing and/or maintaining remission in patients with ulcerative colitis (UC) or Crohn's disease (CD), but data from RCTs are less clear on whether concomitant immunomodulator (IM) therapy confers additional benefit. In CD, RCT data are mixed,1,2 as are results of systematic reviews and meta-analyses, showing no benefit overall,3 minimal benefit with individual agents,4 and comparative benefit over some monotherapies but not others.5 For example, concomitant azathioprine with infliximab is more effective than either drug alone in patients with CD naive to both drugs,2 but whether combination therapy is more effective than monotherapy with infliximab in nonnaive patients, or with other approved biologic drugs in any population, remains unknown. In UC, RCTs have shown that the benefit may be limited to specific populations,6 whereas systematic reviews suggest no benefit at all.7.

Background: Current Crohn's disease (CD) therapies focus on suppressing immune function and come with consequent risk, such as infection and cancer. Notwithstanding, most CD patients still experience disease progression. There is a need for new CD treatment strategies that offer better health outcomes for patients. Aims: To assess safety, efficacy, and tolerability of a novel microbial-derived immunotherapy, QBECO, that aims to restore rather than suppress immune function in CD. Methods: A randomized, double-blind, placebo-controlled trial was conducted in 68 patients with moderate-to-severe CD. Primary endpoints: safety and Week 8 clinical improvement. Secondary endpoints: Week 8 clinical response and remission. Week 8 responders continued blinded treatment through Week 16; non-responders received open-label QBECO from Weeks 9-16. Exploratory analyses included immune biomarker and genotype assessments. Results: QBECO was well-tolerated. Mean reduction in Crohn's Disease Activity Index (CDAI) score was -68 for QBECO vs. -31 for placebo at Week 8. Improvement with QBECO continued through Week 16 (-130 CDAI reduction). Week 8 QBECO clinical response, improvement and remission rates were 41.2%, 32.4%, 29.4% vs. 26.5%, 23.5%, 23.5% for placebo. TNFα inhibitor-naive subjects achieved higher response rates at Week 8 with QBECO (64%) vs. placebo (26%). Specific immune biomarkers were identified that linked to QBECO response. Conclusion: This proof-of-concept study supports further investigation for the use of QBECO as a novel immunotherapy approach for CD. Biomarker analyses suggests it may be feasible to personalize CD treatment with QBECO. Larger trials are now needed to confirm clinical improvement and the unique biological findings. Clinical Trial Number: NCT01809275 (https://clinicaltrials.gov/ct2/show/NCT01809275).

Background & Aims The availability of tests for blood concentrations of anti–tumor necrosis factor (TNF) agents and antibodies against these drugs could improve dose selection for patients with inflammatory bowel disease (IBD). However, there is little consensus on when to test and how to interpret test results. We used the RAND/UCLA Appropriateness Method to determine when these tests are appropriate and how to clinically interpret their results. Methods We conducted a systematic literature search in November 2013 to identify observational or experimental studies of the measurement of anti-TNF drug and antibody concentrations in patients with IBD and interpretation of their results. We developed 35 scenarios that assessed the appropriateness of testing and 143 scenarios that addressed clinical strategies in response to test results, and presented the findings to an expert panel. The appropriateness of each scenario was rated before and after an in-person meeting with the panel. Panelists rated the appropriateness of various clinical management options including changing therapy within class, switching out of class, adjusting drug dose or interval, adding or adjusting concomitant immune modulators, and doing nothing for each of 6 permutations of high versus low drug concentrations and high, low, or undetectable antibody concentrations. Disagreement was assessed using a validated index. Results Assessment of anti-TNF drug and antibody concentrations was rated appropriate at the end of induction therapy in primary nonresponders, in secondary nonresponders, at least once during the first year of maintenance therapy, and following a drug holiday. Routine assessment in responders at the end of induction was rated uncertain. In nearly all scenarios, escalation of drug dosing was rated appropriate when drug concentration was low in the absence of antibodies, and switching within class was rated appropriate when antibodies were present. Other recommendations depended on the specific clinical scenario for which the test was obtained. Conclusions Based on the RAND/UCLA Appropriateness Method of analysis, an expert panel recommends testing for drug and antibody concentrations in many clinical scenarios. The appropriate timing and best way to respond to anti-TNF drug and antibody testing for IBD depends on the specific clinical scenario. These recommendations can help guide clinicians to best optimize anti-TNF therapy.

Background Consensus on what constitutes a quality colonoscopy report for patients with inflammatory bowel disease (IBD) is lacking. We developed a template for quality colonoscopy reporting that can be used broadly by endoscopists. Methods After a literature review of topics relevant to colonoscopy reporting, members of the Building Research in Inflammatory Bowel Disease Globally (BRIDGe) group and 2 external experts proposed candidate reporting elements. The RAND/University of California, Los Angeles appropriateness method was applied to rate the importance and feasibility of elements for inclusion in colonoscopy reports for patients with IBD. Panelists used the modified Delphi method to anonymously rate the importance and feasibility of candidate elements on a 1-to-9 scale (1-3: not important/feasible, 4-6: moderately important/feasible, 7-9: very important/feasible). Disagreement was assessed using a validated index. The panelists then met in person for discussion followed by a second round of voting. Elements rated a median of 7 or higher on importance after rerating were retained. Results One hundred two reporting elements were proposed. A total of 48 elements were retained across the four themes of "disease background," "findings and interventions," "Crohn's disease with an ileocolonic anastomosis," and "pouchoscopy." Conclusions A comprehensive list of recommended elements for quality IBD colonoscopy reporting stratified by clinical scenario has been described, using a rigorous and evidence-based approach. These elements can be incorporated into endoscopy reporting software platforms. Standardized endoscopy reporting may improve the quality of care in IBD.

Vedolizumab, an α4β7-integrin antagonist, is the first gut-selective monoclonal antibody that has been approved for the treatment of moderate-to-severe ulcerative colitis and Crohn’s disease in many countries in the world. However, questions still remain regarding its appropriate use and placement in current treatment algorithms. Therefore, we sought out to evaluate the existing literature on the use of vedolizumab in inflammatory bowel disease. From inception to 21 June 2015 we searched MEDLINE for phase III randomized control trials assessing the utility of vedolizumab in inflammatory bowel disease, of which three were identified. The GEMINI trials demonstrate that vedolizumab is an effective and safe treatment for patients suffering from moderate-to-severe ulcerative colitis (GEMINI I) and Crohn’s disease (GEMINI II and III). However, further studies are needed comparing its efficacy directly with anti-tumor necrosis factor therapies to allow for further delineation of current treatment algorithms as well as ensuring its long-term safety profile.

Background. Infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA) concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67%) and 2 (83%) had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P=0.098). Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.

Introduction: With a need for a larger armamentarium of therapeutic options for those suffering from moderate-to-severe ulcerative colitis, vedolizumab, an α4β7-integrin biologic therapy, has recently received approval in the United States, Canada and Europe. However, it is unclear where it should be positioned in relation to current therapies for moderate-to-severe ulcerative colitis.Areas covered: We systematically reviewed the literature for phase 1, phase 2 and phase 3 randomized controlled trials assessing the role of vedolizumab in ulcerative colitis.Expert opinion: Trials assessing vedolizumab highlight its arrival as an effective and safe therapy for patients suffering from ulcerative colitis.

The use of immunosuppressive therapies for immune-mediated disease is associated with an elevated risk of infections and related comorbidities. While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal, due in part to uncertainty about their efficacy or safety under these clinical situations. To address this concern, a multidisciplinary group of Canadian physicians with expertise in dermatology, gastroenterology, infectious diseases, and rheumatology developed evidence-based clinical guidelines on vaccinations featuring 13 statements that are aimed at reducing the risk of preventable infections in individuals exposed to immunosuppressive and immunomodulatory agents.

Patients admitted to hospital with acute severe ulcerative colitis have a short-term in-hospital colectomy rate of 30%. The Oxford criteria state that if the CRP is greater than 45 mg/l or there are more than eight bowel movements in 24 h at day 3 of intravenous corticosteroids, there is an 85% risk of an in-hospital colectomy. The aim of this study was to determine whether this high rate of colectomy continues to be accurate in this medically refractory patient population. We performed a retrospective chart review of 80 patients admitted to a tertiary hospital between 2013 and 2017 with acute severe ulcerative colitis. Sixteen (20%) patients required an in-hospital colectomy. Of the 33 patients that fulfilled the Oxford criteria, 12 (36%) patients required a colectomy during admission. Only four (9.5%) patients who did not fulfill the Oxford criteria required a colectomy during admission. Twenty-two patients that had fulfilled the Oxford criteria received infliximab as second-line medical therapy. In a patient population that fulfilled the Oxford criteria, the in-hospital colectomy rate has reduced from 85% in 1996 to 36% in 2017. These results should be considered when discussing with patients the opportunity to commence infliximab or cyclosporine as second-line medical therapy.

BACKGROUND: Crohn’s disease (CD) is a condition that affects young individuals. Clinically assessed disease activity by a Gastroenterologist is the gold standard for identifying patients with active inflammation and relapse. Fecal Calprotectin (FC) is a biomarker that is an independent indicator of active inflammation. Bressler et al has shown that FC levels 250 µg/g strongly predict active inflammation/relapse. FC levels between 100–250 µg/g is an indeterminate zone that warrants further testing to confirm the presence/absence of disease. Computed tomography enterography (CTE) is a proposed next test. Recent research has shown that low-dose CTE using model-based iterative reconstruction (MBIR) is non-inferior to standard dose CTE for identifying signs of small bowel inflammation. AIMS: To assess the utility of MBIR CTE signs, in patients with intermediate FC levels, for predicting those who would have active inflammation on clinical assesment. METHODS: A single-center, retrospective cohort study of 163 patients subjected to clinical assessment, FC measurement and low dose CTE to evaluate CD activity between November 2012 & February 2015. The CTE studies for each patient were reviewed by two radiologists for radiographic findings of small bowel CD inflammation. Clinically assessed disease activity by a Gastroenterologist served as the reference standard. Multivariate logistic regression was used to build a scoring equation based on FC levels & radiographic signs to predict active disease in the reference standard. RESULTS: Of the 163 patients, 92 (56%) patients had active inflammation based on clinical assessment. Sixty-five (71%) of the 92 patients clinically diagnosed with active inflammation also had CTE that was deemed active by overall radiologist impression. Fifty (70%) of the 71 patients clinically diagnosed with inactive inflammation also had CTE that was deemed inactive by overall radiologist impression. Sensitivity, specificity, PPV & NPV of overall radiologic impression for CD activity was 0.70, 0.71, 0.75, 0.65, respectively. 138 patients had measured FC levels. Seventy-eight (57%) had clinically active disease & 60 (43%) had clinically inactive disease. In those with active disease, 16 (20%), 13(17%) & 49(63%) had FC levels 250 µg/g, respectively. In those with inactive disease, 53 (88%), 7(12%) & 0(0%) had FC levels 250 µg/g, respectively. An equation based on mural stratification & FC level predicted active disease the best. This equation had a sensitivity, specificity, PPV, NPV & accuracy of 0.82, 0.90, 0.91, 0.79 & 0.85, respectively. CONCLUSIONS: In patients with FC levels between 101–250, MBIR CTE is a reasonable further test to confirm the presence/absence of disease FUNDING AGENCIES: None

One of the therapy goals for Crohn’s disease (CD) is glucocorticoid-free remission. Studies have shown care setting-specific variations in inflammatory bowel disease (IBD) management. The principal objective of this study was to assess concordance between patient-reported and physician-reported outcomes in two different care settings (IBD centers and community practices). Data of overall and long-term (≥ 3 months) glucocorticoid, immunosuppressant, and biologics use in participants ≥ 18 years old with a confirmed diagnosis of CD were collected. HCPs were grouped by IBD centers and community practices. Quality of life (using EuroQol 5D [EQ-5D]) and work/activity days lost were assessed. Agreement between patients’ and HCPs’ responses to survey questions was tested using kappa statistics. Data from 812 patients were examined. Significantly more patients versus HCPs reported oral glucocorticoid use (25.9% vs. 20.8%, κ = 0.735, P

Background. Inflammatory bowel disease (IBD) patients are not routinely screened for depression and anxiety despite knowledge of an increased prevalence in people with chronic disease and negative effects on quality of life.Methods.Prevalence of anxiety and depression was assessed in IBD outpatients through retrospective chart review. The presence of anxiety and/or depression was determined using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 self-report questionnaires or by diagnosis through psychiatric interview. Patient demographics, disease characteristics, and medication information were also collected. Multivariable analysis was used to determine associations between patient factors and depression and anxiety.Results.327 patient charts were reviewed. Rates of depression and anxiety were found to be 25.8% and 21.2%, with 30.3% of patients suffering from depression and/or anxiety. Disease activity was found to be significantly associated with depression and/or anxiety (p=0.01). Females were more likely to have anxiety (p=0.01).Conclusion.A significant proportion of IBD patients suffer from depression and/or anxiety. The rates of these mental illnesses would justify screening and referral for psychiatric treatment in clinics treating this population. Patients with active disease are particularly at risk for anxiety and depression.