Novel and emerging drugs for the treatment of Crohn's disease: a review of phase II and III trials.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. While several therapeutic options, such as anti-tumor necrosis factor (TNF), anti-integrin, and interleukin (IL) 12/23 inhibitors, as well as IL-23 and Janus kinase (JAK) inhibitors, have been approved for CD treatment, a substantial number of patients fail to respond adequately or experience a loss of response over time. In recent years, the scientific community has been actively investigating novel agents to address these challenges and improve the management of CD. AREAS COVERED: This comprehensive narrative review provides an overview of recent developments in CD treatment, summarizing phase 2 and phase 3 clinical trial data. We delve into the clinical efficacy and safety profiles of emerging therapies, encompassing JAK inhibitors, IL-23 inhibitors, anti-adhesion molecules, S1P1 receptor modulators, and combined targeted treatments. EXPERT OPINION: The armamentarium of CD therapeutic agents is constantly expanding. We analyze pivotal findings from phase 2 and phase 3 CD treatment trials. We also underscore the existing gaps in therapy and the paramount role of ongoing research and innovation in CD management.

Serrated Polyps in Inflammatory Bowel Disease Indicate a Similar Risk of Metachronous Colorectal Neoplasia as in the General Population.

BACKGROUND: The risk of metachronous advanced neoplasia after diagnosing serrated polyps in patients with IBD is poorly understood. METHODS: A retrospective multicenter cohort study was conducted between 2010 and 2019 at three tertiary centers in Montreal, Canada. From pathology databases, we identified 1587 consecutive patients with serrated polyps (sessile serrated lesion, traditional serrated adenoma, or serrated epithelial change). We included patients aged 45-74 and excluded patients with polyposis, colorectal cancer, or no follow-up. The primary outcome was the risk of metachronous advanced neoplasia (advanced adenoma, advanced serrated lesion, or colorectal cancer) after index serrated polyp, comparing patients with and without IBD. RESULTS: 477 patients with serrated polyps were eligible (mean age 61 years): 37 with IBD, totaling 45 serrated polyps and 440 without IBD, totaling 586 serrated polyps. The median follow-up was 3.4 years. There was no difference in metachronous advanced neoplasia (HR 0.77, 95% CI 0.32-1.84), metachronous advanced adenoma (HR 0.54, 95% CI 0.11-2.67), and metachronous advanced serrated lesion (HR 0.76, 95% CI 0.26-2.18) risk. When comparing serrated polyps in mucosa involved or uninvolved with IBD, both groups had similar intervals from IBD to serrated polyp diagnosis (p > 0.05), maximal therapies (p > 0.05), mucosal inflammation, inflammatory markers, and fecal calprotectin (p > 0.05). CONCLUSION: The risk of metachronous advanced neoplasia after serrated polyp detection was similar in patients with and without IBD. Serrated polyps in IBD occurred independently of inflammation. This helps inform surveillance intervals for patients with IBD diagnosed with serrated polyps.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

Health utilities and willingness to pay in adult patients with coeliac disease in Hungary.

BACKGROUND: Coeliac disease (CD) is a life-long food-related disorder with a global prevalence of approximately 1%. Patients with CD often experience reduced health-related quality of life that could improve with a strict adherence to a gluten-free diet (GFD). OBJECTIVES: To obtain visual analogue scale (VAS), time trade-off (TTO) and willingness-to-pay (WTP) values amongst patients with CD. METHODS: In 2020-2021, a cross-sectional online survey was conducted amongst 312 adult CD patients in Hungary. Patients completed the Gastrointestinal Symptom Rating Scale (GSRS) and evaluated their current health and three hypothetical health state vignettes defined based on dietary adherence using VAS, conventional 10-year TTO and WTP. Multivariate regressions were used to explore the effect of patients' demographic and clinical characteristics on utility and WTP values. RESULTS: Mean VAS values for current health and 'CD with strict adherence to GFD', 'CD with loose adherence to GFD' and 'CD without GFD' hypothetical health states were 79.69 ± 18.52, 85.36 ± 16.18, 62.44 ± 19.91 and 36.69 ± 25.83, respectively. Corresponding mean TTO utilities were: 0.90 ± 0.19, 0.91 ± 0.20, 0.87 ± 0.23 and 0.76 ± 0.29. Mean annual WTP values for returning to full health were: €845 ± 1077, €648 ± 1002, €862 ± 1135 and €1251 ± 1496. Older age at diagnosis, male sex, more severe gastrointestinal symptoms (GSRS) and having comorbidities were associated with lower VAS and TTO or higher WTP values for current own health (p < 0.05). CONCLUSION: This is the first study to report TTO utilities for CD health states. Strict adherence to the GFD may result in substantial health gains in symptomatic patients. Utilities and WTP results can be used to estimate benefits of GFD in cost-utility and cost-benefit analyses.

A systematic review and functional bioinformatics analysis of genes associated with Crohn's disease identify more than 120 related genes.

BACKGROUND: Crohn's disease is one of the two categories of inflammatory bowel diseases that affect the gastrointestinal tract. The heritability estimate has been reported to be 0.75. Several genes linked to Crohn's disease risk have been identified using a plethora of strategies such as linkage-based studies, candidate gene association studies, and lately through genome-wide association studies (GWAS). Nevertheless, to our knowledge, a compendium of all the genes that have been associated with CD is lacking. METHODS: We conducted functional analyses of a gene set generated from a systematic review where genes potentially related to CD found in the literature were analyzed and classified depending on the genetic evidence reported and putative biological function. For this, we retrieved and analyzed 2496 abstracts comprising 1067 human genes plus 22 publications regarding 133 genes from GWAS Catalog. Then, each gene was curated and categorized according to the type of evidence associated with Crohn's disease. RESULTS: We identified 126 genes associated with Crohn's disease risk by specific experiments. Additionally, 71 genes were recognized associated through GWAS alone, 18 to treatment response, 41 to disease complications, and 81 to related diseases. Bioinformatic analysis of the 126 genes supports their importance in Crohn's disease and highlights genes associated with specific aspects such as symptoms, drugs, and comorbidities. Importantly, most genes were not included in commercial genetic panels suggesting that Crohn's disease is genetically underdiagnosed. CONCLUSIONS: We identified a total of 126 genes from PubMed and 71 from GWAS that showed evidence of association to diagnosis, 18 to treatment response, and 41 to disease complications in Crohn's disease. This prioritized gene catalog can be explored at http://victortrevino.bioinformatics.mx/CrohnDisease .

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

BACKGROUND & AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Impact of Endoscopic and Histologic Activity on Disease Relapse in Ulcerative Colitis.

INTRODUCTION: Endoscopic healing is currently considered the main target in the management of ulcerative colitis (UC). There are conflicting data about the role of histology as a stricter treatment objective. We aim at evaluating the additional benefit of histologic remission over endoscopic remission. METHODS: We performed a prospective observational study at the McGill University Health Center. We enrolled adult patients with UC in clinical remission for at least 3 months undergoing a colonoscopy. Endoscopic disease activity was based on the Mayo endoscopic score. Rectal biopsies were obtained, and the histologic activity was evaluated using the Geboes score (active disease defined as Geboes score ≥ 3.1) with the addition of assessing the presence of basal plasmacytosis. Patients were followed up for 12 months for disease relapse defined as a partial Mayo score of > 2. At the time of relapse or end of follow-up, all patients underwent repeat endoscopic evaluation. The primary end point was clinical relapse. RESULTS: Two hundred fifty-three patients were included. The presence of basal plasmacytosis was associated with relapse (adjusted odd ratio = 2.07, 95% confidence interval [CI] 1.06-4.18, P = 0.042). Time to clinical relapse was significantly higher for patients with Mayo endoscopic score > 0 with adjusted hazard ratio = 2.65, 95% CI 1.31-5.39, and P = 0.007. Time to clinical relapse was not significantly higher for Geboes score ≥ 3.1 with adjusted hazard ratio = 1.29, 95% CI 0.67-2.49, and P = 0.45. DISCUSSION: Active histologic disease did not affect time to clinical relapse in patients with UC who achieved endoscopic remission while the presence of basal plasmacytosis is associated with relapse.

The Global Incidence of Peptic Ulcer Disease Is Decreasing Since the Turn of the 21st Century: A Study of the Organisation for Economic Co-Operation and Development (OECD).

INTRODUCTION: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS: The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS: The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = -3.9%; 95% CI: -4.4, -3.3) and morality rates (AAPC = -4.7%; 95% CI: -5.6, -3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021. DISCUSSION: PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.

Fucosyltransferase 2 Mutations Are Associated With a Favorable Clinical Course in Crohn's Disease.

BACKGROUND: Fucosyltransferase 2 (FUT2) participates in intestinal antigen secretion and bacterial adherence. FUT2 homozygous nonsense mutations (FUT2M) and subsequent nonsecretor status is associated with Crohn's disease (CD). The common null allele is rs601338. We assessed the relationship between FUT2M and disease course. METHODS: In consecutive adult CD outpatients, clinical, biochemical, and genetic data were collected at baseline visits. Patients were longitudinally followed over 5 years. The primary outcome analyzed the relationship between FUT2M and rates of CD patients in persistent steroid-free clinical remission requiring neither surgery, biologics, nor immunomodulators. RESULTS: Sixty-two CD patients were recruited. FUT2M homozygotes (rs601338 or any mutation in linkage disequilibrium) were detected in 27% of CD (17/62). Patients with rs601338 mutations had higher rates of the primary outcome (homozygous: 46.6%, heterozygous: 28.0%, wild-type: 5.3%, P=0.02). Similar findings existed for CD patients with homozygous mutations in any single-nucleotide polymorphism for FUT2 (homozygous: 41.2%, heterozygous: 25.9%, wild-type: 5.6%, P=0.04). On multivariable analysis, rs601338 mutation was associated with the primary outcome (odds ratio=3.4, 95% confidence interval: 1.3-8.7, P=0.01), while other parameters were not. Mutation of rs601338 was associated with lower rates of penetrating disease (homozygous: 13.3%, heterozygous: 28.0%, wild-type: 52.6%, P=0.05) and particularly in high-risk patients (homozygous: 0%, heterozygous: 37.5%, wild-type: 83.3%, P=0.01). CONCLUSIONS: FUT2 mutation status is associated with a favorable clinical course in CD. Further confirmatory studies are needed.

Patient Perspectives and Expectations in Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND: In this systematic review, our objective was to assess inflammatory bowel disease (IBD) patient preferences and perspectives relating to their disease diagnosis, treatment, knowledge needs and telemedicine. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases and conference proceedings were searched between January 1, 1980, and May 1, 2020. The methodological quality of the included studies was assessed using the Standards for reporting qualitative research checklist. RESULTS: Our search identified 240 citations and 52 studies met the inclusion criteria. The major expectations of the patients are symptomatic and pain control, quality of life and normal endoscopy. Patients' main concerns are access to information and healthcare, and shared decision making. At the time of diagnosis, patients expressed a greater need for knowledge about their IBD, preferentially by their treating gastroenterologist. The main treatment expectations in active disease are efficacy, safety and convenience. Patients are willing to accept relatively high risks of complications from medical therapy to avoid a permanent ostomy and to achieve durable remission. Patients are more interested in disease monitoring, research and development during the time of remission. Telemedicine and self-management with supervised e-health tools are feasible and acceptable amongst patients with IBD. CONCLUSION: This systematic review demonstrates that patients with IBD expect more information about their disease process, shared decision making and symptom control. Further research is needed to help align patient and physician expectations in order to improve the quality of care provided to patients with IBD.

Effectiveness of Tofacitinib for Hospitalized Patients with Acute Severe Ulcerative Colitis: Case Series.

BACKGROUND: Treatment options for acute severe ulcerative colitis (ASUC) are limited. Tofacitinib, an approved treatment for moderate to severe ulcerative colitis, could be a potential rescue therapy for ASUC given its rapid onset of action. OBJECTIVE: To evaluate the effectiveness of tofacitinib in hospitalized patients with ASUC refractory to standard therapy in a real-world setting. METHODS: Retrospective observational study of hospitalized adult patients with ASUC treated with tofacitinib between January 2019 and September 2020 at five Canadian centers. We extracted patient demographics, clinical status, biomarkers (C-reactive protein and fecal calprotectin), endoscopic findings, and colectomy-free rate at admission, 30 days, 90 days, and 6 months after tofacitinib initiation. RESULTS: Eight patients with symptoms refractory to standard rescue therapy (corticosteroids ± infliximab if infliximab-naïve prior to admission) were treated with tofacitinib. During index hospitalization, clinical response was observed in 5/8 patients. The median time to discharge post-tofacitinib initiation was 5 days (IQR 5.0-6). At 30 and 90 days, all five responders were in clinical remission. At 6 months, only 3/5 responders remained in clinical remission. The colectomy-free rate was 37.5% during the follow-up period (two colectomies occurred within 30 days; one occurred within 90 days). No drug-related adverse reaction occurred. CONCLUSION: In this small case-series, tofacitinib was an effective rescue therapy in patients with refractory ASUC. These findings need to be evaluated in a randomized controlled trial.

Patient-Reported Outcome and Clinical Scores Are Equally Accurate in Predicting Mucosal Healing in Ulcerative Colitis: A Prospective Study.

BACKGROUND: Optimal management of patients with ulcerative colitis (UC) requires the accurate, objective assessment of disease activity. AIMS: We aimed to determine how strong patient-reported outcomes, clinical scores and symptoms correlate with endoscopy and biomarkers for assessment of disease activity in patients with UC. METHODS: Consecutive patients with UC followed at the McGill University IBD Center and referred for endoscopy (surveillance or flare) were included prospectively between September 2018 and August 2020. Patient-reported outcome (PRO2), partial Mayo, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES) and Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C-reactive protein (CRP) and fecal calprotectin (FCAL) were collected. RESULTS: A total of 171 patients with UC [age: 49(IQR:38-61) years, female: 46.2%, 57.3% extensive disease, 42.7% on biologicals] were included prospectively. Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS0 and SF ≤ 1), partial Mayo (≤ 2) and SCCAI (≤ 2.5) remission were similarly associated with mucosal healing defined by MES (0 or ≤ 1), Baron (0 or ≤ 1) or UCEIS (≤ 3) scores in ROC analysis (AUC:0.93-0.72). There was a moderate-to-strong agreement between MES Baron and UCEIS (K = 0.91-0.41). A UCEIS of ≤ 3 was identified as the best cutoff to clinical or endoscopic remission. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K ~ 0.2), while agreement between FCAL and RBS-PRO2 or MES/Baron/UCEIS was moderate to strong (K = 0.44-0.70). CONCLUSIONS: Agreement between RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing was moderate to strong, while no clinically meaningful difference was found in accuracy across the scores and definitions. FCAL, but not CRP, was associated to clinical and endoscopic remission.

Poor Drug Sustainability in Inflammatory Bowel Disease Patients in Clinical Remission on Thiopurine Monotherapy.

BACKGROUND: Immunomodulator monotherapy is an important component in the treatment of inflammatory bowel disease (IBD). However, there is conflicting literature about thiopurines maintaining long-term remission in patients with active IBD. AIM: To determine the durable clinical remission rate in adults with Crohn's disease (CD) or ulcerative colitis (UC) on thiopurine monotherapy over 5 years. METHODS: We performed a retrospective analysis of adult patients identified at McGill University Health Centre from 2009 to 2012. We included IBD patients who initiated thiopurine monotherapy and were in remission for at least 3 months (Harvey-Bradshaw Index (HBI) < 5 points for CD and partial Mayo Score (pMS) < 2 points in UC). The primary endpoint was sustained clinical remission on thiopurines during a 5-year follow-up. This included patients who had not relapsed or discontinued the drug due to side effects. The secondary endpoint was clinical relapse over the follow-up period, which was defined as HBI > 5 in CD and pMS > 2 in UC. RESULTS: There were 148 patients included in the study (100 CD; 48 UC). At 5 years, 23% (34/148) patients remained in clinical remission on thiopurine monotherapy (25 CD and 9 UC patients). Thirty-three percent (33/100) of CD and 46% (22/48) of UC patients relapsed while on thiopurines. There was no difference in relapse rates between CD and UC patients. Eighty-four percent (42/50) of patients with CD with side effects and all UC (17/17) patients who experienced side effects discontinued the drug. CONCLUSION: This analysis demonstrates that there is poor sustainability of clinical remission in IBD patients on thiopurine monotherapy given that a high proportion of patients discontinue thiopurines due to either relapse or side effects.

Plasma Levels of C-Type Lectin REG3α and Gut Damage in People With Human Immunodeficiency Virus.

BACKGROUND: Regenerating islet-derived protein 3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH. METHODS: Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)-uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers. RESULTS: Cross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4:CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal product translocation and inflammatory markers in all PWH. CONCLUSIONS: Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.

A User's Guide to De-escalating Immunomodulator and Biologic Therapy in Inflammatory Bowel Disease.

De-escalation of immunomodulators and biologic agents in inflammatory bowel disease is frequently discussed with patients and must weigh the risk of continued medical therapy with the risk of disease recurrence. Risk factors for disease flare after withdrawal of inflammatory bowel disease medications such as disease activity at de-escalation, disease prognostic features, and prior course of disease have been identified predominately in retrospective studies, allowing for risk stratification of patients. This review evaluates the published literature regarding therapeutic de-escalation and provides a framework for physicians to apply this to clinical practice. Prospective trials are underway and planned, which should provide further insight into this treatment paradigm and better inform patient selection for this strategy.

Low Rate of Drug Discontinuation, Frequent Need for Dose Adjustment, and No Association with Development of New Arthralgia in Patients Treated with Vedolizumab: Results from a Tertiary Referral IBD Center.

BACKGROUND: Evaluating clinical data on the safety and efficacy of vedolizumab (VDZ) in 'real-world' setting is still desirable. Recent reports have raised concerns that arthralgia may be associated with VDZ. AIMS: The aim of this study is to present clinical experience with VDZ from a tertiary IBD center. METHODS: Retrospective chart reviews were performed of consecutive patients exposed to VDZ between 2015 and 2018. Clinical, biomarker, and endoscopic efficacy and safety data were evaluated. RESULTS: A total of 130 IBD (75CD, 55UC) patients were included. Median duration of VDZ therapy was 65 weeks. Probability of drug discontinuation was 4.9% and 9.4% at 1 and 2 years. Dose intensification was more frequent in CD compared to UC (at 1 and 2 years: 64.8/87.9% vs. 26.5/35.7%, p < 0.001). Clinical remission rates at 3-, 6- and 12 months were 44.4%, 71.4% and 77.1% in UC, and 9.1%, 26.7% and 29.2% in CD patients, respectively. Prior use of multiple biologic agents was associated with diminished efficacy of VDZ in CD. Three new cases of arthralgia were encountered during follow-up. CONCLUSION: Vedolizumab (VDZ) therapy displayed good drug sustainability and clinical efficacy in a population with severe disease phenotype and high rates of previous anti-TNF failure. Frequent dose intensification was required. The safety profile was good, and no association between newly onset arthralgia and VDZ therapy was observed.

Clinical Parameters Correlate With Endoscopic Activity of Ulcerative Colitis: A Systematic Review.

BACKGROUND & AIMS: Optimal management of patients with ulcerative colitis (UC) requires assessment of disease activity-usually by endoscopy, which is invasive, costly, and not risk free. We performed a systematic review to determine whether clinical symptoms correlate with findings from endoscopy assessments of patients with UC. METHODS: We performed a systematic review of publication databases from January 1980 through July 2018 to identify clinical trials and observational studies reporting correlations among symptoms, disease activity index scores and/or patient reported outcomes (rectal bleeding and/or stool frequency), and endoscopic disease activity. Correlations were ascertained in patients with active vs inactive disease and by disease extent and treatment type. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Because of significant heterogeneity, meta-analysis was not possible. Results were synthesized qualitatively and systematically. RESULTS: Our final analysis included 23 studies (1 randomized trial, 22 observational studies) comprising 3320 patients with UC. The studies used a variety of measures to assess clinical activity, endoscopic activity, and measures of correlation (sensitivity, specificity, correlation coefficients, area under the receiver operator curve). Overall, studies were at moderate-high risk of bias. Composite clinical measures, including rectal bleeding and stool frequency, had moderate to strong correlations with endoscopic disease activity; the absence of rectal bleeding identified patients with inactive disease with higher levels of sensitivity than normalization of stool frequency. In general, symptoms correlated more strongly with endoscopic activity in patients with left-sided colitis than extensive colitis. The effect of different medications on the correlation between clinical and endoscopic activity has not been well studied. CONCLUSIONS: In a systematic review, we found a moderate to strong correlation between clinical activity, particularly the combination of rectal bleeding and stool frequency, and endoscopic activity in patients with UC. Although these clinical assessments could help prioritize patients for endoscopic evaluation in resource-limited settings, challenges associated with treating patients based on symptoms alone preclude adaptation of current management algorithms.

Sex-Based Differences in Incidence of Inflammatory Bowel Diseases-Pooled Analysis of Population-Based Studies From Western Countries.

BACKGROUND & AIMS: Although the incidence of inflammatory bowel diseases (IBDs) varies with age, few studies have examined variations between the sexes. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age at diagnosis. METHODS: We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95,605 incident cases of Crohn's disease (CD) (42,831 male and 52,774 female) and 112,004 incident cases of ulcerative colitis (UC) (61,672 male and 50,332 female). We pooled incidence rate ratios of CD and UC for the combined cohort and compared differences according to sex using random effects meta-analysis. RESULTS: Female patients had a lower risk of CD during childhood, until the age range of 10-14 years (incidence rate ratio, 0.70; 95% CI, 0.53-0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25-29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5-9 years) until age 45 years; thereafter, men had a significantly higher incidence of ulcerative colitis than women. CONCLUSIONS: In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence.

Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus.

BACKGROUND: The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC. METHODS: PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings. RESULTS: In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients' daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs. CONCLUSIONS: These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC.