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Background: The Saudi Food and Drug Authority (SFDA) has approved the subcutaneous (SC) administration of infliximab, presenting a more convenient alternative with reduced outpatient visits and diminished expenses compared to the intravenous (IV) administration. However, the financial implications of this formulation have not been examined from the perspective of Saudi payers., Methods and Materials: A prevalence-based budget impact model was developed to evaluate the financial effects of introducing "environment without" versus "with infliximab SC." The model's time horizon spanned over 2 years (2021-2023), aligning with the biennial national pharmaceutical procurement cycle. The comparison focused on infliximab SC versus all available formulations of infliximab IV in the Saudi market for two inflammatory bowel diseases (IBD): Ulcerative Colitis (UC) and Crohn's Disease (CD). Treatment comparators' comparability and dose escalations were substantiated by published studies, utilizing dosing information from the summary of product characteristics. Drug acquisition costs were derived from SFDA registered prices, with IV formulation administration costs included. Scenario analysis assessed the budget impact of infliximab SC introduction at uptake rates ranging from 0% to 100%., Results: Introducing infliximab SC demonstrated cost-saving potential in the treatment of IBD. At 100% uptake with UC patients for 2 years, infliximab SC resulted in savings of -SAR-31.9 million (-SAR29,145 per patient). Similarly, for CD, introducing infliximab SC at 100% uptake over 2 years yielded savings of -SAR106.2 million (-SAR36,585 per patient)., Conclusion: This study reveals that infliximab SC is associated with cost-saving potential when compared to infliximab IV formulations available in Saudi Arabia. Future research should address uncertainties related to real-world comparative effectiveness, the convenience of administration, patient tolerability, and physician acceptance of the SC formulation of infliximab, alongside comparisons with other TNF-alpha inhibitors., Competing Interests: N Alkhatib holds equity in Pi Pharma Intelligence, LLC, which provides health technology solutions, scientific and consulting services to biopharmaceutical, diagnostics, and medical device companies on a nonexclusivity basis. By the company internal policy, owners, employees, and associates are prohibited from holding equity in client and sponsor organizations or contracting independently with client and sponsor organizations or receiving compensation independently from such organizations. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Alkhatib et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Vedolizumab is an approved ulcerative colitis (UC) treatment. Multiple large randomized clinical trials have demonstrated the drug's efficacy and safety. However, real-world data from Middle Eastern countries are spare. The study aims to evaluate the clinical efficacy of vedolizumab (VDZ) therapy in advanced therapy experienced UC patients., Methods: A retrospective electronic chart review of a cohort study of 153 moderately to severely active UC patients who failed or were intolerant to TNF antagonists and received vedolizumab from two large tertiary care centers was performed. Rates of clinical response and remission were retrospectively evaluated at 3,6, and 12 months post VDZ therapy using Patient Simple Clinical Colitis Activity Index (P-SCCAI); clinical response was defined as a decrease in P-SCCAI ≥3, and clinical remission was defined as a P-SCCAI score of ≤3 points. Logistic regression analysis was used to identify predictors of response to vedolizumab., Results: A total of 153 UC patients had sufficient data for analysis. Clinical remission rates were 61.9% for patients on vedolizumab every 8 weeks and 89.3% for those receiving every 4 (Q4) weeks dosing. A significant reduction in CRP and improvement of albumin post vedolizumab treatment were observed, and corticosteroids were stopped in most patients. In a multiple logistic regression analysis, several factors were found to influence the clinical effectiveness of VDZ in inducing remission. Female gender was associated with a higher likelihood of remission [OR =3.09, 95% CI = (1.05-9.13), P = 0.04]. Conversely, a greater number of biologics used prior to VDZ treatment was associated with a lower likelihood of remission [OR =0.418, 95% CI = (0.203-0.859), P = 0.017]. Patients with extensive disease (E3) had an increased likelihood of remission [OR =3.81, 95% CI = (1.32-10.97), P = 0.0129]. Additionally, a VDZ dosing frequency of Q4 weeks was associated with a significantly higher likelihood of remission [OR =6.08, 95% CI = (1.73-21.39), P = 0.0049]. No significant safety signals were reported., Conclusions: In this current real-world study, vedolizumab effectively achieved clinical response and remission in most advanced therapy experienced UC patients treated for up to 12 months. Future studies with larger sample sizes and more robust study designs should be conducted to further validate the results of this study., (Copyright © 2024 Copyright: © 2024 Saudi Journal of Gastroenterology.)

Abstract: The management of inflammatory bowel disease (IBD) in children and adolescents is challenging. Clear evidence-based guidelines are required for this population. This article provides recommendations for managing IBD in Saudi children and adolescents aged 6-19 years, developed by the Saudi Ministry of Health in collaboration with the Saudi Society of Clinical Pharmacy and the Saudi Gastroenterology Association. All 57 guideline statements are based on the most up-to-date information for the diagnosis and management of pediatric IBD., (Copyright © 2024 Copyright: © 2024 Saudi Journal of Gastroenterology.)

Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease that affects the colon, leading to symptoms of bloody diarrhea, abdominal cramps, and urgency. The treatment of UC has evolved over the past few decades from locally active anti-inflammatory compounds to more selective therapies that target specific arrays of the immune system. The challenge of selecting the first advanced therapy became apparent in this rapidly expanding landscape of medications. No current investigational tools, such as genetic, immunologic, or biological markers, can guide the identification of the safest and most effective therapeutic option for each patient. Hence, physicians must carefully assess patient/disease characteristics and match them with the most suitable drug through a clinically driven assessment. In this paper, we outline patient and drug characteristics that play a role in selecting first-line advanced therapies for UC and propose an algorithm for selection., (Copyright © 2024 Copyright: © 2024 Saudi Journal of Gastroenterology.)

In response to the COVID-19 pandemic, several countries have started implementing voluntary or involuntary mass vaccination programs. Although vaccine acceptance is high among adults, uncertainty about whether to vaccinate children against COVID-19 remains a controversial theme. To date, few qualitative studies have explored parents' views on this topic. A qualitative descriptive study design was used to collect data and individual in-depth interviews were conducted with 50 parents in the Makkah region of Saudi Arabia. The Health Belief Model (HBM) was used as a guide in developing the interview guide. Each question was related to a construct of the HBM. The data were then analyzed using thematic content analysis and interpreted using NVivo software. Two major themes emerged: motivation to vaccinate children, which was influenced by perceived benefits, perceived severity, perceived suitability, collective responsibilities, confidence, and cues to action; and barriers to vaccination in children, which included complacency, rapid vaccine development, and uncertainty about the long-term side effects of the vaccine. The findings of this study revealed that the public is not sufficiently informed about the efficacy or side effects of the COVID-19 vaccine, increasing the awareness of which will help parents make informed decisions regarding vaccinating their children and potentially increase vaccine acceptance.

Abstract: The management of inflammatory bowel disease (IBD) in pregnant women is challenging and must be addressed on a patient-by-patient basis. Optimal patient management requires a multidisciplinary team and clear evidence-based recommendations that cater to this subset of patients. In this article, we provide concise guidelines and clinical care pathway for the management of IBD in pregnant women. Our recommendations were developed by a multidisciplinary working group that includes experts from the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacology. All recommendations are based on up-to-date information following an extensive literature review. A total of 23 evidence-based expert opinion recommendations for the management of IBD in pregnant women are herein provided., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Gastroenterology.)

Background: As the population ages, the number of elderly inflammatory bowel disease (IBD) patients is expected to increase. The clinical features and therapeutic options for young and old patients may differ, as elderly IBD patients are likely to have different comorbidities and disease characteristics. The goal of this study was to examine the clinical aspects and therapeutic choices for elderly Saudi IBD patients., Methods: We conducted a retrospective study aimed at describing the demographic, clinical, and management characteristics of IBD in elderly patients (≥60 years) who followed up at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. The data was extracted from the KAUH inflammatory bowel disease information system (IBDIS) registry. The primary outcome was to describe disease characteristics in accordance with the Montréal classification and the secondary outcomes were to describe treatment patterns and identify significant clinical associations., Results: Our data were collected from 76 patients who fulfilled the study inclusion criteria. Females outnumbered males (53.9% vs 46.1%) and the mean age was 51.5 ± 9.7 years. Essential hypertension (26.3%) was the most common comorbidity followed by diabetes mellitus (23.6%), and malignant neoplasms (9.21%). More than half of the patients with Crohn's disease (CD) had disease onset after forty years of age. The most common form of disease distribution was ileocolonic disease (64.7%). Less than 17% of patients had a penetrating disease phenotype. About 88 percent of patients with UC presented >40 years of age. Approximately, half of the cohort had left-sided ulcerative colitis (UC) (48%), followed by pancolitis (40%). The most prescribed medication class for IBD was 5-aminosalicylic acid (5-ASA) derivatives (56.58%) followed by corticosteroids and immunosuppressive drugs., Conclusions: In Saudi Arabia, age-specific concerns including comorbidities and polypharmacy remain the major challenges in the management of elderly IBD patients., Competing Interests: None

Background: Inflammatory bowel disease (IBD) is a chronic autoimmune disorder characterized by severe inflammation and mucosal destruction of the intestine. The specific, complex molecular processes underlying IBD pathogenesis are not well understood. Therefore, this study is aimed at identifying and uncovering the role of key genetic factors in IBD., Method: The whole exome sequences (WESs) of three consanguineous Saudi families having many siblings with IBD were analyzed to discover the causal genetic defect. Then, we used a combination of artificial intelligence approaches, such as functional enrichment analysis using immune pathways and a set of computational functional validation tools for gene expression, immune cell expression analyses, phenotype aggregation, and the system biology of innate immunity, to highlight potential IBD genes that play an important role in its pathobiology., Results: Our findings have shown a causal group of extremely rare variants in the LILRB1 (Q53L, Y99N, W351G, D365A, and Q376H) and PRSS3 (F4L and V25I) genes in IBD-affected siblings. Findings from amino acids in conserved domains, tertiary-level structural deviations, and stability analysis have confirmed that these variants have a negative impact on structural features in the corresponding proteins. Intensive computational structural analysis shows that both genes have very high expression in the gastrointestinal tract and immune organs and are involved in a variety of innate immune system pathways. Since the innate immune system detects microbial infections, any defect in this system could lead to immune functional impairment contributing to IBD., Conclusion: The present study proposes a novel strategy for unraveling the complex genetic architecture of IBD by integrating WES data of familial cases, with computational analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jan, Al-Numan, Al-Twaty, Alrayes, Alsufyani, Alaifan, Alhussaini, Shaik, Awan, Qari, Saadah, Banaganapalli, Mosli and Elango.)

Objectives: To determine the prevalence of hiatal hernia (HH) and its association with age, gender, and body mass index (BMI)., Methods: We retrospectively included patients who underwent esophagogastroduodenoscopy (EGD) at an academic tertiary care hospital. Data were collected on the presence of HH as well as patient demographics including age, gender, and BMI. Univariate and multivariate analysis were done to determine risk factors for HH., Results: A total of 2805 patients were included in this study. The mean age was 48.6 (±18.6) years and males constituted 28.8% of the study population. The mean BMI was 29.7 (±8.6) kg/m². The prevalence of HH was 29.8% among all patients and 48.6% among those who underwent EGD for gastroesophageal reflux disease-related indications. There was no significant association between HH and female gender (OR 1.04, 95%CI: 0.88 -1.26, p =0.53), older age (OR 0.77, 95%CI: 0.72 - 1.06, p =0.19) or BMI (OR 1.07, 95%CI: 0.9 - 1.2, p =0.39)., Conclusion: The prevalence of HH was 28.9% based on this large endoscopy-based population. We found no association between HH and gender, age, or BMI., (Copyright: © Saudi Medical Journal.)

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The tofacitinib OCTAVE clinical program included phase III induction (OCTAVE Induction 1 and 2) and maintenance (OCTAVE Sustain) studies, and an open-label, long-term extension study (OCTAVE Open)., Objective: This post hoc analysis assessed selected long-term, disease-specific patient-reported outcome (PRO) and health-related quality-of-life (HRQoL) measurements in patients with UC receiving tofacitinib in the OCTAVE clinical program., Methods: Analyses included patients from OCTAVE Open assigned to tofacitinib 5 mg twice daily (subpopulation in remission at Week 52 of OCTAVE Sustain). OCTAVE Open data from the final analyses are shown to Month 48. Endpoints included rectal bleeding subscore (RBS) = 0, stool frequency subscore (SFS) ≤ 1, and HRQoL measure, Inflammatory Bowel Disease Questionnaire (IBDQ) remission (IBDQ total score ≥ 170); with non-responder imputation for missing data at all visits, and last observation carried forward for visits after a patient advanced to the next study (NRI-LOCF). Observed cases were also assessed., Results: At Month 48, of 175 patients, 95 (54.3%) and 96 (54.9%) achieved/maintained RBS = 0 and SFS ≤ 1, respectively (NRI-LOCF). Additionally, 93 (53.1%) patients achieved/maintained IBDQ remission at Month 48 (NRI-LOCF)., Conclusions: Among patients who entered OCTAVE Open in remission, most maintained normalization of rectal bleeding and improvement in stool frequency for ≤ 4 years of follow-up in OCTAVE Open. IBDQ remission was also generally maintained in OCTAVE Open. These data show robust maintenance of key UC PROs and durability of response with tofacitinib 5 mg twice daily., Trial Registration: http://www., Clinicaltrials: gov (NCT01465763 [21/10/2011]; NCT01458951 [21/10/2011]; NCT01458574 [21/10/2011]; NCT01470612 [21/10/2011])., (© 2022. The Author(s).)

Background and Objectives: Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition that debilitate the quality of life. Multimorbidity, a concept only beginning to emerge in IBD, is defined as two or more comorbidities present in the same individual. Notably, we used the term multimorbidity to refer to two or more comorbidities excluding IBD. Multimorbidity is linked to decreased quality of life, poorer disease outcomes, increased hospitalizations, healthcare costs and polypharmacy complications. We aim to estimate the prevalence of multimorbidity and to explore its effect on IBD patients., Methods: We retrospectively reviewed all IBD patients registered in a validated web-based registry since February 2018. Data on patient demographics, comorbidities, IBD and extraintestinal complications were obtained. We analyzed the date using univariate, bivariate and multivariable analysis., Results: Among 767 IBD patients, 54.6% had Crohn's disease (CD), 41.9% had ulcerative colitis (UC) and 3.5% had IBD unclassified. The median age at diagnosis was 22 years (IQR: 15-29). Males compromised 50.2% of patients. According to the Montréal IBD classification, most UC patients had moderate UC (47.8%) while most CD patients had non-stricturing non-penetrating CD (49.8%). Overall, 10.3% IBD patients had multimorbidity and 23.9% had at least one comorbidity. The most common comorbidity was diabetes mellitus (4.9%) followed by essential hypertension (4%) and iron deficiency anemia (3%). Female gender (P = 0.008) and UC (P = 0.005) were more likely to have multimorbidity. Multimorbid IBD patients were more likely to develop thrombosis than non-multimorbid peers (16.7% vs. 1.6%; P < 0.001). Higher age at diagnosis (OR = 1.04, 95%CI: 1.01-1.07) and having a history of thrombosis (OR = 7.82, 95% CI: 2.67-22.92) are associated with increased risk of multimorbidity., Conclusion: Multimorbidity is not uncommon among IBD patients, especially females diagnosed with UC. Our findings indicate that future studies are needed to explore the effects of multimorbidity on IBD patients., (© 2022. The Author(s).)

Optimal management of inflammatory bowel disease (IBD) relies on a clear understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This article provides concise guidelines for the management of IBD in adults, based on the most up-to-date information at the time of writing and will be regularly updated. These guidelines were developed by the Saudi Ministry of Health in collaboration with the Saudi Gastroenterology Association and the Saudi Society of Clinical Pharmacy. After an extensive literature review, 78 evidence-and expert opinion-based recommendations for diagnosing and treating ulcerative colitis and Crohn's disease in adults were proposed and further refined by a voting process. The consensus guidelines include the finally agreed on statements with their level of evidence covering different aspects of IBD diagnosis and treatment., Competing Interests: None

Background: Molecular diagnosis of early onset inflammatory bowel disease (IBD) is very important for adopting suitable treatment strategies. Owing to the sparse data available, this study aims to identify the molecular basis of early onset IBD in Arab patients., Methods: A consanguineous Arab family with monozygotic twins presenting early onset IBD was screened by whole exome sequencing (WES). The variants functional characterization was performed by a series of computational biology methods. The IBD variants were further screened in in-house whole exome data of 100 Saudi cohorts ensure their rare prevalence in the population., Results: Genetic screening has identified the digenic autosomal recessive mode of inheritance of ITGAV (G58V) and FN1 (G313V) variants in IBD twins with early onset IBD. Findings from pathogenicity predictions, stability and molecular dynamics have confirmed the deleterious nature of both variants on structural features of the corresponding proteins. Functional biology data suggested that both genes show abundant expression in gastrointestinal tract and immune organs, involved in immune cell restriction, regulation of different immune related pathways. Data from knockout mouse models for ITGAV gene has revealed that the dysregulated expression of this gene impacts intestinal immune homeostasis. The defective ITGAV and FN1 involved in integrin pathway, are likely to induce intestinal inflammation by disturbing immune homeostasis., Conclusions: Our findings provide novel insights into the molecular etiology of pediatric onset IBD and may likely pave way in developing genomic medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al-Numan, Jan, Al-Saud, Rashidi, Alrayes, Alsufyani, Mujalli, Shaik, Mosli, Elango, Saadah and Banaganapalli.)

Background and Aims: Although much of the research on the plausible environmental triggers for inflammatory bowel disease (IBD) has focused on bacterial pathogens, the relationship between bowel colonization with human papillomavirus (HPV) and IBD has not been previously explored. In this study, we aimed to investigate the association between HPV ileocolonic colonization and IBD., Patients and Methods: We performed a cross-sectional study involving consecutive patients with established IBD who were referred for endoscopic evaluation. During endoscopy, mucosal biopsies were obtained from the most inflamed colonic or ileal segments in cases and from the rectosigmoid region for controls. A hybrid capture assay was used to detect tissue HPV. The prevalence of HPV colonization was determined for cases and controls and was compared using Fisher's exact test., Results: A total of 201 patients, including 104 patients with IBD and 97 non-IBD controls, were prospectively included. Females comprised 55.5% of the study participants (58% vs. 55.2% for controls, P = 0.94). Fifty-seven (54.8%) patients had ulcerative colitis, and 45 (43.2%) had Crohn's disease. The mean age was 43.2 +-18.2 years. Endoscopically active disease was documented in 56 cases (56%). HPV colonization was detected in four (4.1% subjects in controls vs. none in the cases, P = 0.05)., Conclusions: There was no evidence of HPV ileocolonic colonization in this cohort of patients with IBD, regardless of disease activity. HPV colonization does not appear to be linked to IBD diagnosis or disease severity., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background and study aims Currently, there are no studies conducted in the Kingdom of Saudi Arabia (KSA) that have assessed the relationship between ulcerative colitis (UC) flare-ups and smoking. The present study aims to assess the risk of UC flare-ups and evaluate the relationship between UC flare-ups and smoking in adult patients following up at King Abdulaziz University Hospital in Jeddah, KSA. Patients and methods This was a retrospective study involving patients with confirmed UC between January 2015 and December 2020. Various information was examined, including demographic, clinical, endoscopic, radiologic, and laboratory data. Descriptive statistics were used for summarizing findings and a logistic regression analysis was applied to test for possible associations. Results Eighty-nine patients with UC were included in the study. Almost half (48.3%) had recurrent UC flare-ups during follow-up. A non-significant relationship was found between recurrent UC flares and all types of smoking habits (cigarette smoking, P = 0.15; shisha smoking, P = 0.88; and vape smoking, P = 0.09). Participants who were underweight ( P = 0.041), had family history of UC ( P = 0.013), depression ( P = 0.033), fecal incontinence ( P = 0.003), iron deficiency anemia ( P = 0.009), or a malignancy ( P = 0.039) had a significantly higher probability of experiencing recurrent flares. Binary logistic regressions revealed that family history of UC (OR = 5.3, P = 0.007) and fecal incontinence (OR = 4.7, P = 0.006) were associated significantly with recurrent flares. Conclusion There was no clear association between smoking and recurrent UC flares identified in this cohort. Of the variables considered, UC patients with fecal incontinence or family history of UC were at the highest risk of developing recurrent flares., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Malibary et al.)

Background: Inflammatory bowel disease (IBD), which can have a considerable effect on quality of life, productivity and performance, is typically diagnosed during periods of life in which patients have academic and career-related responsibilities., Objective: The objective of the study was to determine the effect of IBD symptoms on work and school absenteeism in patients from Saudi Arabia., Patients and Methods: This cross-sectional survey included patients diagnosed with IBD, aged >8-60 years, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. The validated 32-question IBD quality-of-life questionnaire was used to elicit information regarding quality of life and another 9-question validated questionnaire was used to assess work and school absenteeism. A logistic regression analysis was used to identify possible determinants of absenteeism., Results: A total of 123 IBD patients were included, with a 1:1 male-to-female ratio. The median age at presentation was 26 years (range: 8-59 years), 56.9% had Crohn's disease, and 43.1% had ulcerative colitis. Further, 58 (47.2%) were employed, 49 (39.8%) were students and 16 (13%) were unemployed. Forty-seven (43.9%) participants reported absenteeism: 26 were employees (55.3%) and 21 were students (44.7%). A binary logistic regression analysis identified IBD subtype ( P = 0.006) and the presence of perianal disease ( P = 0.028) as clinical predictors for absenteeism from school or work. A feeling of abdominal pain ( P = 0.015), fatigue ( P = 0.015) and difficulty taking part in social engagements ( P < 0.001) were also significantly associated with absenteeism., Conclusions: A sizeable proportion of the participants reported absenteeism owing to the effects of IBD. IBD subtype, perianal disease, presence of ongoing abdominal pain, fatigue and difficulty in social engagement were strongly associated with nonattendance., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Saudi Journal of Medicine & Medical Sciences.)

Solitary rectal ulcer syndrome (SRUS) is an uncommon disorder of the rectum. While benign, it can cause concern for patients and affect quality of life. Reported studies on SRUS worldwide are scarce. The aim of this study is to describe the clinicopathologic characteristics of SRUS in a cohort of children based in Saudi Arabia. In this study, children with a confirmed diagnosis of SRUS at King Abdulaziz University Hospital (KAUH) were included, during the period November 2003 to November 2017. Data were collected from hospital medical records. The study comprised twenty-one patients: 17 males (81%) and 4 females (19%); the median age was 11.4 years (range, 5.43-17.9 years). The most common presenting symptoms were rectal bleeding in 21 patients (100%), passage of mucus in 16 (76.1%), abdominal pain in 14 (66.6%), constipation in 13 (61.9%), straining in 9 (42.9%), and rectal prolapse in 5 (23.8%). The most common finding at initial colonoscopy was a single ulcer in 7 patients (33.3%), multiple ulcers in 6 (28.5%), polypoid lesions in 5 (23.8%), and hyperemic mucosa in 3 (14.2%). All patients received medical treatment and 14 (81%) continued to manifest one or more of the symptoms following treatment, which required subsequent modification of the treatment course. None of the patients required surgery. In conclusion, the study found rectal bleeding to be the most common presentation, with a single ulcer being the most prevalent lesion in endoscopy. Treatment response was variable, but almost half of patients reported relief of symptoms following treatment., Competing Interests: None., (IJCEP Copyright © 2021.)

Reduced bone mineral density (BMD) has broadly been found to be associated with inflammatory bowel disease across a number of geographical locations and cultures. We aimed to estimate the prevalence of reduced BMD and identify clinical predictors in a cohort of Crohn's disease patients (CD) in Saudi Arabia. We conducted a retrospective study involving children and adolescents with CD between 2013 and 2018. BMD was evaluated using dual-energy X-ray absorptiometry scans of the spine and body. A multivariate analysis was performed for the detection of predictors of low BMD. Sixty-four patients were enrolled. The median age was 16 years (range, 8-19 years) and 55% of patients were males. Total body BMD scanning identified 25 patients (39%) with osteoporosis. Twenty patients (31.3%) were found to have z scores consistent with osteopenia. A multivariate regression analysis identified a low weight-for-age z score (B coefficient = 0.347, 95% confidence interval [CI] = 0.211-0.482, p < 0.001 for Spine BMD and B coefficient = 0.321, 95% CI = 0.170-0.472, p < 0.001 for total body BMD), a low height-for-age z score (B coefficient = 0.187, 95% CI = 0.035-0.338, p = 0.017 for spine BMD and B coefficient = 0.0.258, 95% CI = 0.089-0.427, p = 0.004 for total body BMD), a low 25-hyroxyvitamin D level (B coefficient = 0.026, 95% CI = 0.013-0.038, p < 0.001 for spine BMD and B coefficient = 0.016, 95% CI = 0.002-0.031, p = 0.026 for total body BMD), and a higher number of corticosteroid induction courses (B coefficient = -0.567, 95% CI = -0.923 to -0.212, p = 0.003 for spine BMD and B coefficient = -0.566, 95% CI = 0.963-0.169, p = 0.007 for total body BMD) as predictors of low BMD. In the spine BMD analysis, older age at the time of presentation was identified as a significant predictor for low bone density (B coefficient = 0.254, 95% CI = 0.141-0.368, p < 0.001). In conclusion, Saudi Arabian children and adolescents with CD have a high prevalence rate of low bone density compared to Western populations. Several clinical characteristics are identified as significant predictors for low BMD., (Copyright © 2020 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Background: Intra-abdominal collections in the form of abscesses or matted bowel loops, called phlegmons, might occur in patients with Crohn's disease (CD). The clinical characteristics and management of such conditions are not well described. We aim to characterize CD-related intra-abdominal collections clinically, and identify predictors of need for surgical interventions and the time to surgery., Methods: We utilized the Saudi Inflammatory Bowel Disease Information System (IBDIS) database to identify all patients treated for radiologically proven intra-abdominal abscesses or phlegmons since inception. Demographics, clinical data, clinical course, and treatment outcomes were recorded. Logistic regression analysis and survival analysis were used to identify predictors of surgical resection and differences in time to surgery between patient subgroups, respectively., Results: A total of 734 patients with a diagnosis of CD were screened and 75 patients were identified. The mean age was 25.6 ± 9.9 years and 51% were males. Nearly 60% of patients had abscesses larger than 3 cm while 13% had smaller abscesses and 36% had phlegmons. On presentation, the most commonly reported symptom was abdominal pain (99%) followed by weight loss (27%). About 89% of patients were treated with antibiotics during hospitalization for an average of 2.7 weeks. Steroids were prescribed for 52% of patients and tumor necrosis factor alpha (TNF-alpha) antagonists for 17%. Surgical resection was required for 33 patients (44% of the cohort) while 51% were managed with antibiotics and/or percutaneous drainage. The most common surgical intervention was ileocecal resection (45%). Although patients who underwent follow-up imaging were more likely to require early surgical intervention (P = 0.04), no statistically significant predictor of surgery could be identified from this cohort. Time to surgery varied numerically according to abscess size (HR = 1.18, 95% CI = 0.62-2.27, P = 0.61)., Conclusions: Although the majority of patients with CD-related intra-abdominal collections underwent surgical resection in this cohort, no obvious predictors of surgical intervention could be identified. The decision to perform early surgery appeared to be influenced by the findings observed on cross-sectional imaging during the follow-up of these collections., Competing Interests: None

Objective: Metabolic bone disease concerns a broad spectrum of conditions related to reduced bone density. Metabolic bone disease has been linked to chronic inflammatory diseases, such as ulcerative colitis. This study examines the prevalence of metabolic bone disease in ulcerative colitis patients and explores possible clinical predictors., Method: The authors performed a retrospective study involving children and adolescents with confirmed ulcerative colitis between January 2013 and December 2018. Bone density was evaluated through a dual-energy X-ray absorptiometry scan of the spine and total body. Osteoporosis was defined as a bone mineral density Z-score of <-2 and osteopenia as a Z-score of between -1.0 and -2., Results: A total of 37 patients were included in this analysis, with a mean age of 13.4±3.9 years and a mean duration of illness of 2.1±2.4 years. Using lumbar spine Z-scores and total body Z-scores, osteoporosis and osteopenia were identified by dual-energy X-ray absorptiometry scan measurements in 11 patients (29.7%) and 15 patients (40.5%), and in ten patients (27%) and 13 patients (35%), respectively. Lumbar spine Z-scores were significantly positively associated with male gender (B=2.02; p=0.0001), and negatively associated with the presence of extraintestinal manifestations (B=-1.51, p=0.009) and the use of biologics (B=-1.33, p=0.004). However, total body Z-scores were positively associated with body mass index Z-scores (B=0.26, p=0.004) and duration of illness in years (B=0.35, p=0.003)., Conclusions: Metabolic bone disease is very common in this cohort of Saudi Arabian children and adolescents with ulcerative colitis and its occurrence appears to increase in female patients who suffer from extraintestinal manifestations., (Copyright © 2020 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: Inflammatory bowel disease (IBD) has been associated with restless leg syndrome (RLS). This study aims to explore the prevalence, clinical predictors, and severity of RLS in IBD patients compared to controls., Methods: We conducted a case-control study between January and December of 2019 comparing IBD patients with controls. Assessment of RLS was performed using the previously validated diagnostic restless leg syndrome questionnaire (RLSQ). Logistic regression analyses were applied to investigate associations between patient demographics and clinical features and RLS diagnosis., Results: A total of 218 IBD patients and 211 healthy controls were incorporated after excluding 6 patients with positional discomfort and 4 patients with habitual foot tapping. The mean age was 30.2+/-11.7 and 64% were females. The prevalence of RLS was 16/218 (7.34%) and 17/211 (8.06%) among cases and controls, respectively. Based on the RLSQ severity score, 6/16 (37.5%), 4/16 (25%) and 1/16 (6.3%) of the IBD patients with RLS had mild, moderate and severe RLS; respectively. The odds of IBD were lower among patients with confirmed RLS (OR=0.90, 95% CI=0.44-1.84, p=0.78). In the logistic regression analysis, only vitamin B12 deficiency (OR=10.20, 95% CI=1.40-74.10, p=0.022) was associated with RLS diagnosis among IBD patients., Conclusion: No difference was found in the prevalence of RLS between IBD patients and non-IBD controls. Vitamin B12 deficiency was associated with RLS diagnosis among patients with IBD.

Objective: The aim of this study is to evaluate the impact of adopting a pharmaceutical care model on clinical outcomes, patient satisfaction, and cost at a health payer level., Methods: All patients with hepatitis C virus (HCV) who were insured by Bupa Arabia, with a direct-acting antivirals prior authorization drug request between April 2015 and October 2018 were included in this retrospective quasi-experimental study. The clinical outcome was the achievement of a sustained virologic response at least 12 weeks from end of treatment. Economic and patients' satisfaction outcomes were included in this study. The differences in cost of treatment was analyzed by using the paired t test. Stata statistical software package (StataCorp, College Station, TX) was used for data analysis., Results: A total of 371 patients were enrolled in this program of which 74% (n = 273) required clinical intervention. Among those, HCV treatment was modified for 64%. The overall cure rate was 97% among 267 patients for which sustained virologic responses were available. The results of the paired t test show that there was a 38% reduction in the mean direct cost of medications before and after intervention (95% confidence interval, 33%-43%; P<.001) and the calculated patients' satisfaction was 98%., Conclusions: A structured pharmaceutical care program for HCV patients can guide the use of specialty medications to achieve optimal clinical outcomes, with lower expenditures and high patients' satisfaction. We can conclude that healthcare insurance can play a key role in managing specialty pharmaceuticals like HCV medications. Because this is a preliminary study, further studies are needed in an experimental design to strengthen the evidence behind the effectiveness of such a program., (Copyright © 2020 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Background/aims: Crohn's disease (CD) may involve the upper parts of the gastrointestinal (GI) tract including the esophagus, stomach, and duodenum. Clinical features of upper GI CD (UGICD) are not well characterized in the Gulf region. We therefore aimed to assess the prevalence and clinical characteristics of patients diagnosed with UGICD., Methods: We performed a retrospective analysis of all patients diagnosed with CD who underwent upper GI endoscopy between 2012 and 2017 at King Abdulaziz University Hospital, irrespective of age. Patients who had endoscopy of the upper GI tract at baseline and had histologically confirmed UGICD were included. Data on patients' demographics, clinical characteristics, extraintestinal manifestations and complications were reviewed., Results: We identified 78 CD patients who underwent upper GI endoscopy from our medical records. The mean age was 17.2±8.7 years and 55.1% were males. Of the total, 19 out of 78 patients (24.4%) had histologically confirmed UGICD (3 esophageal, 16 gastric, and 9 duodenal), of which 52.6% were symptomatic. Disease distribution was ileal in 57.8%, colonic in 21.1% and ileo-colonic in 21.1%. A non-stricturing and non-penetrating phenotype was reported in 89.4%, stricturing in 5.3%, and penetrating in 5.3%. Perianal disease was found in 10.5%. UGICD was complicated by stricture formation in 2 patients (esophageal and gastric)., Conclusions: The prevalence of UGICD is considered high among CD Saudi patients who undergo upper GI endoscopy at baseline, and is asymptomatic in 47.4% of patients. This reported prevalence is not dissimilar from reports originating from Western countries.

Objectives: Colorectal polyps are a known precursor to colorectal cancer (CRC). Using the Saudi dietary guidelines adherence scores, this study evaluated whether dietary intake can lead to the development of colorectal polyps in a Saudi cohort., Methods: In a cross-sectional study, 101 patients of both sexes, aged 30-86 years (40 patients with colorectal polyps and 61 patients without polyps), were recruited from the endoscopy unit in a Saudi hospital. A questionnaire was administered to collect demographic data, anthropometric data, and information about dietary habits., Results: Patients with colorectal polyps were significantly older than those without polyps (p  = 0.05). The mean body mass index in both patient groups was within the overweight range, with a value of 28.6 ± 6.7 kg/m 2 . We did not find significant differences between patients with and without colorectal polyps. Although there was no difference in the overall scores for adherence to the Saudi dietary guidelines between the two groups, the specific adherence score for vegetables was significantly higher in patients without colorectal polyps (5.0 ± 0.0 vs. 4.9 ± 0.3, p  = 0.03)., Conclusion: Ageing and lower vegetable intake, previously reported to be risk factors for CRC, were likewise identified in this study. However, a multi-centre study with a larger sample size, utilising data from this study, is needed., (© 2019 The Authors.)

Background: Pediatric foreign body aspiration (FBA) is a life-threatening condition responsible for many deaths every year, especially among children younger than 2 years., Objective: This study aimed to determine the level of knowledge among students in Jeddah, Saudi Arabia., Subjects and Methods: This observational, cross-sectional study was conducted between December and January 2018 at Jeddah, Saudi Arabia via a paper-based questionnaire survey of male and female high school and middle school students. The Chi-square test was used to compare frequencies, and the independent t -test was used to compare means., Results: A total of 671 students participated in this survey. The second item, "It is possible for a child to choke on a small toy" had the highest rate of correct responses among both males and females (93.2% vs. 94%, respectively). The eighth item "Sudden cough is a sign of choking among children" had the lowest rate of correct responses among males (40.8%) and females (33%). Most female participants (74.2%) knew that batteries are the most dangerous items a child can swallow, which requires immediate medical attention (item 14), while only 56.2% of male participants knew that ( P < 0.001). The only significant predictor on linear regression analysis was "Having treated anyone with FBA" (coefficient = -0.24, P = 0.03)., Conclusions: There is inadequate knowledge regarding FBA among middle and high school students, as is the case among mothers. Moreover, only a small percentage of participants had any first aid training., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Education and Health Promotion.)

Objectives: To translate and validate the malnutrition universal screening tool (MUST) for use in Arabic-speaking outpatients with inflammatory bowel disease (IBD)., Methods: We translated the MUST into Arabic by using the Brislin back-translation method. This methodological study was performed between August 2016 and November 2017 on 143 outpatients with IBD at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. The patients must completed the self-administered (PSA) Arabic version of the MUST. Then, the health-care practitioners (HCPs) administered the Arabic MUST and performed standard patient clinical assessment. The nutrition risk was defined as low (MUST score=0), medium (MUST score=1), or high (MUST score greater than 1). The chance-corrected proportional agreement between the scores from the PSA and HCP-administered Arabic MUST was evaluated using Cohen's kappa coefficient. Internal consistency was evaluated using Cronbach's alpha statistic., Results: The overall agreement between the PSA and HCP-administered Arabic MUST was almost perfect (agreement=95.9%, expected agreement=72.4%, kappa=0.85, p less than 0.0001). The calculated Cronbach's alpha statistic for MUST scores in 15/143 (10%) patients was 0.79. The calculated Pearson's correlation coefficient between PSA and HCP-administered MUST scores was 0.93 (p less than 0.0001)., Conclusions: The PSA and HCP-administered Arabic MUST showed perfect agreement in outpatients with IBD.

Background and Aims: Pouchitis is a common adverse event after proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis. Evaluation of pouchitis disease activity and response to treatment requires use of validated indices. We assessed the reliability of items evaluating endoscopic pouchitis disease activity., Methods: Twelve panelists used a modified RAND appropriateness methodology to rate the appropriateness of items evaluating endoscopic pouchitis disease activity derived from a systematic review and also identified additional potential endoscopic items based on expert opinion. Four central readers then evaluated 50 pouchoscopy videos in triplicate, in random order. Intra- and inter-rater reliability for each item was assessed by calculating and comparing intraclass correlation coefficients (ICCs). A Delphi process identified common sources of disagreement among the readers., Results: Ten existing endoscopic items were identified from the systematic review and an additional 7 exploratory items from the panelists. ICCs for inter-rater reliability were highest for the existing item of pouch ulceration (.72; 95% confidence interval [CI], .60-.82) and for the exploratory item of ulcerated surface in the pouch body (.67; 95% CI, .53-.75). Inter-rater reliability for all other existing and exploratory items was "moderate" (ICC < .60). The item "ulcerated surface in the pouch body" demonstrated the best correlation with a global evaluation of lesion severity (r = .80; 95% CI, .73-.85)., Conclusion: Substantial reliability was observed only for the endoscopic items of ulceration and ulcerated surface in the pouch body. Future studies should assess responsiveness to treatment in the next stage toward development of an endoscopic pouchitis disease activity index., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Endoscopic assessment of mucosal disease activity is routinely used to determine eligibility and response to therapy in clinical trials of ulcerative colitis. The operating properties of the existing endoscopic scoring indices are unclear., Objectives: A systematic review was undertaken to evaluate the development and operating characteristics of endoscopic scoring indices for the evaluation of ulcerative colitis., Search Methods: We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2016. We also searched references and conference proceedings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organization)., Selection Criteria: Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated endoscopic indices for evaluation of ulcerative colitis disease activity were considered for inclusion. Eligible participants were adult patients (> 16 years), diagnosed with ulcerative colitis using conventional clinical, radiologic and endoscopic criteria., Data Collection and Analysis: Two authors independently reviewed the studies identified from the literature search. These authors also independently extracted and recorded data on the number of patients enrolled; number of patients per treatment arm; patient characteristics including age and gender distribution; endoscopic index; and outcomes such as reliability (intra-rater and inter-rater), validity (content, construct, criterion), responsiveness and feasibility. Any disagreements regarding study inclusion or data extraction were resolved by discussion and consensus with a third author. Risk of bias was assessed by determining whether assessors were blinded to clinical information and whether assessors scored the endoscopic index independently. We also assessed the methodological quality of the validation studies using the COSMIN checklist MAIN RESULTS: A total of 23 reports of 20 studies met the pre-defined inclusion criteria and were included in the review. Of the 20 included validation studies, 19 endoscopic scoring indices were assessed, including the Azzolini Classification, Baron Score, Blackstone Endoscopic Interpretation, Chinese Grading System of Ulcerative Colitis, Endoscopic Activty Index, Jeroen Score, Magnifying Colonoscopy Grade, Matts Score, Mayo Clinic Endoscopic Subscore, Modified Baron Score, Modified Mayo Clinic Endoscopic Subscore, Osada Score, Rachmilewtiz Endoscopic Score, St. Mark's Index, Ulcerative Colitis Colonoscopic Index of Serverity (UCCIS), endoscopic component of the Ulcerative Colitis Disease Activity Index (UCDAI), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Witts Sigmoidoscopic Score and Watson Grade. The individuals who performed the endoscopic scoring were blinded to clinical and/or histologic information in ten of the included studies, not blinded to clinical and/or histologic information in one of the included studies, and it was unclear whether blinding occurred in the remaining nine included studies. Independent observation was confirmed in four of the included studies, unclear in five of the included studies, and non-applicable (since inter-rater reliability was not assessed) in the remaining eleven included studies. The methodological quality (COSMIN checklist) of most of the included studies was rated as 'good' or 'excellent'. One study that assessed responsiveness was rated as 'fair'. The inter-rater reliability of nine endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Endoscopic Activity Index, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS, UCEIS, Watson Grade was assessed in seven studies, with estimates of correlation, ƙ, ranging from 0.44 to 0.97. The iIntra-rater reliability of seven endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS and UCEIS was assessed in three studies, with estimates of correlation, ƙ, ranging from 0.41 to 0.86. No studies assessed content validity. Three studies evaluated the criterion validity of three endoscopic scoring indices including the Rachmilewitz Endoscopic Score, Magnifying Colonoscopy Grade and the UCCIS. These indices were correlated with objective markers of disease activity including albumin, blood leukocytes, C-reactive protein, fecal calprotectin, hemoglobin, mucosal interleukin-8 concentration and platelet count. Correlation estimates ranged from r = -0.19 to 0.83. Thirteen endoscopic scoring indices were tested for construct validity in 13 studies. Estimates of correlation between the endoscopic scoring indices and other measures of disease activity ranged from r = 0.27 to 0.93. Two studies explored the responsiveness of four endoscopic scoring indices including the Mayo Endoscopic Subscore, Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS. One study concluded that the Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS had similar responsiveness for detecting disease change in ulcerative colitis. The other included study concluded that the UCEIS may be the most accurate endoscopic scoring tool. None of the included studies formally assessed feasibility., Authors' Conclusions: While the UCEIS, UCCIS and Mayo Clinic Endoscopic Subscore have undergone extensive validation, none of these instruments have been fully validated and only two studies assessed responsiveness. Further research on the operating properties of these indices is needed given the lack of a fully-validated endoscopic scoring instrument for the evaluation of disease activity in ulcerative colitis.

Background: It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors influencing placebo rates may lead to more informed clinical trial design., Objectives: A systematic review and meta-analysis was conducted to evaluate placebo response and remission rates in RCTs evaluating UC treatments in adult patients., Search Methods: Electronic databases (i.e. MEDLINE, EMBASE, and CENTRAL) were searched from inception to 1 March 2017 with no language restrictions applied. Reference lists and conference proceedings of major gastroenterology meetings were also handsearched to identify additional studies., Selection Criteria: Placebo-controlled RCTs of adult patients with UC treated with corticosteroids, aminosalicylates, immunosuppressives or biologics were eligible, provided enrolment and outcome assessment was conducted using the Ulcerative Colitis Disease Activity Index (UCDAI) or the Mayo Clinic Score. The minimum trial duration was two weeks for induction trials and four months maintenance trials., Data Collection and Analysis: Pairs of authors independently determined study eligibility and extracted data with any disagreements resolved through consensus. Outcomes of interest included the proportion of patients with clinical response and remission. Trial characteristics such as the design, participant demographics and disease history, interventions, and enrolment and assessment criteria were also recorded. The methodological quality of the included studies was evaluated using the Cochrane risk of bias tool. Pooled placebo response and remission rates and 95% confidence intervals (95% CI) were calculated using a binomial normal model for proportions. Induction of remission and maintenance studies were pooled separately. The impact of study-level characteristics on placebo response and remission rates was investigated using mixed-effects meta-regression analyses with logits of event rates as the outcome variables. An assessment of pooled placebo rates over time was conducted using a cumulative meta-analysis based on date of publication. Publication bias was examined using funnel plots., Main Results: The screening process identified 61 included studies which encompass 58 induction phases (5111 patients randomised to placebo) and 12 maintenance phases (1579 patients randomised to placebo). For induction trials, the pooled estimate of placebo response was 33% (95% CI 30% to 36%) while the pooled estimate of placebo remission was 12% (95% CI 9% to 15%). For maintenance trials, the pooled estimate of placebo response was 23% (95% CI 19% to 28%) while the pooled estimate of placebo remission was 17% (95% CI 10% to 27%).Studies enrolling patients with more active disease confirmed objectively by endoscopy were associated with significantly lower placebo remission and response rates than trials enrolling patients with less active disease (27% versus 4%, OR 2.60, 95% CI 1.25 to 5.42, P = 0.01 for UCDAI endoscopy sub score ≥1 versus ≥ 2 for remission; and 27% versus 4%, OR 1.70, 95% CI 1.02 to 2.82, P = 0.02 for UCDAI endoscopy sub score greater than or equal to one versus greater than or equal to two for response). With respect to drug class, the lowest placebo response and remission rates were observed in trials evaluating corticosteroids (23%; 95% CI 19 to 29%, and 5%; 95% CI 2 to 11%, respectively). Trials of biologics had the highest placebo response rate (35%; 95% CI 30 to 41%), while trials evaluating aminosalicylates had the highest placebo remission rate (18%; 95% CI 12 to 24%). Disease duration of greater than five years prior to enrolment was associated with a significantly lower placebo response rate compared to disease duration of less than or equal to five years (29% versus 47%, respectively; OR 0.54, 95% CI 0.32 to 0.92, P = 0.02). The requirement of a minimum rectal bleeding score for study eligibility was associated with an increased placebo response rate compared to studies that did not use rectal bleeding for trial eligibility (37% versus 32%, respectively; OR 1.70, 95% CI 1.02 to 2.82, P = 0.02). Finally, the time point of primary outcome assessment was found to be significantly associated with placebo remission rates such that every one week increment in endpoint assessment was associated with a 6% increase in the placebo remission rate (OR 1.06, 95% CI 1.02 to 1.10, P = 0.01).Cumulative meta-analysis indicated a consistent increase in the placebo response rate from 1987 to 2007 (from 13% to 33%), although rates have remained constant from 2008 to 2015 (32% to 34%). Similarly, placebo remission rates increased from 1987 to 2007 (5% to 14%) but have remained constant from 2008 to 2015 (12 to 14%). On meta-regression, there were no statistically significant differences between the 1987-2007 and 2008-2015 point estimates for both response (P = 0.81) and remission (P = 0.32)., Authors' Conclusions: Placebo response and remission rates vary according to endoscopic disease severity and rectal bleeding score at trial entry, class of agent, disease duration, and the time point at which the primary outcome was measured. These observations have important implications for the design and conduct of future clinical trials in UC and will help researchers design trials, determine required sample sizes and also provide useful information about trial design features which should be considered when planning new trials.

Background: Disease activity can be determined using clinical, endoscopic or histologic criteria in patients with ulcerative colitis (UC). Persistent disease activity is associated with poor outcomes. Histologic disease activity has been shown to be associated with relapse, colectomy and colorectal cancer. The ability to objectively evaluate microscopic disease activity using histology is important for both clinical practice and clinical trials. However, the operating properties of the currently available histologic indices remain unclear., Objectives: A systematic review was undertaken to identify and evaluate the development and operating characteristics of histologic disease activity indices used to assess disease activity in people with ulcerative colitis., Search Methods: We searched MEDLINE, EMBASE, PubMed, CENTRAL and the Cochrane IBD Review Group Specialized Trials Register from inception to 2 December 2016 for applicable studies. There were no language or document type restrictions., Selection Criteria: Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated a histologic index in patients with UC were considered for inclusion. Eligible patients were adults (> 18 years), diagnosed with UC using conventional clinical, radiographic, endoscopic and histologic criteria., Data Collection and Analysis: Two authors (MHM and CEP) independently reviewed the titles and abstracts of the studies identified from the literature search. A standardized form was used to assess eligibility of trials for inclusion and for data extraction.Two authors (MHM and CEP) independently extracted and recorded data, which included the number of patients enrolled, number of patients per treatment arm, patient characteristics including age and gender distribution, and the name of the histologic index. Outcomes (i.e. intra-rater reliability, inter-rater reliability, internal consistency, content validity, criterion validity, construct validity, responsiveness, and feasibility) were recorded for each trial., Main Results: In total, 126 reports describing 30 scoring indices were identified through the screening process. Eleven of the 30 scoring indices have undergone some form of index validation. Intra-rater reliability was assessed for eight scoring indices. Inter-rater reliability was evaluated for all 11 of the scoring indices. Three of the indices underwent content validation. Two of the included scoring indices assessed criterion validity. Six of the included scoring indices explored content validity. Two of the included scoring indices were tested for responsiveness., Authors' Conclusions: The Nancy Index and the Robarts Histopathology Index have undergone the most validation in that four operating properties including reliability, content validity, construct validity (hypothesis testing) and criterion validity have been tested. However, none of the currently available histologic scoring indices have been fully validated. In order to determine the optimal endpoint for histologic healing in UC, more research is required. The optimal index would need to be fully validated.

Background: Minimising placebo response is essential for drug development., Aim: To conduct a meta-analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates., Methods: MEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo-controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random-effects and mixed-effects meta-regression models to evaluate effects of study-level characteristics on these rates., Results: In 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16-21%] and 28% (95% CI 24-32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25-39%) and 26% (95% CI 19-35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics., Conclusions: Placebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease., (© 2017 John Wiley & Sons Ltd.)

Objective: Although the Geboes score (GS) and modified Riley score (MRS) are commonly used to evaluate histological disease activity in UC, their operating properties are unknown. Accordingly, we developed an alternative instrument., Design: Four pathologists scored 48 UC colon biopsies using the GS, MRS and a visual analogue scale global rating. Intra-rater and inter-rater reliability for each index and individual index items were measured using intraclass correlation coefficients (ICCs). Items with high reliability were used to develop the Robarts histopathology index (RHI). The responsiveness/validity of the RHI and multiple histological, endoscopic and clinical outcome measures were evaluated by analyses of change scores, standardised effect size (SES) and Guyatt's responsiveness statistic (GRS) using data from a clinical trial of an effective therapy., Results: Inter-rater ICCs (95% CIs) for the total GS and MRS scores were 0.79 (0.63 to 0.87) and 0.80 (0.69 to 0.87). The correlation estimates between change scores in RHI and change score in GS and MRS were 0.75 (0.67 to 0.82) and 0.84 (0.79 to 0.88), respectively. The SES and GRS estimates for GS, MRS and RHI were: 1.87 (1.54 to 2.20) and 1.23 (0.97 to 1.50), 1.29 (1.02 to 1.56) and 0.88 (0.65 to 1.12), and 1.05 (0.79 to 1.30) and 0.88 (0.64 to 1.12), respectively., Conclusions: The RHI is a new histopathological index with favourable operating properties., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background and Aims: Minimisation of the placebo responses in randomised controlled trials [RCTs] is essential for efficient evaluation of new interventions. Placebo rates have been high in ulcerative colitis [UC] clinical trials, and factors influencing this are poorly understood. We quantify placebo response and remission rates in UC RCTs and identify trial design factors influencing them., Methods: MEDLINE, EMBASE, and the Cochrane Library were searched from inception through April 2014 for placebo-controlled trials in adult patients with UC of a biological agent, corticosteroid, immunosuppressant, or aminosalicylate. Data were independently doubly extracted. Quality was assessed using the Cochrane risk of bias tool., Results: In all, 51 trials [48 induction and 10 maintenance phases] were identified. Placebo response and remission rates were pooled according to random-effects models, and mixed-effects meta-regression models were used to evaluate effects of study-level characteristics on these rates. Pooled estimates of placebo remission and response rates for induction trials were 10% (95% confidence interval [CI] 7-13%) and 33% [95% CI 29-37%], respectively. Corresponding values for maintenance trials were 19% [95% CI 11-30%] and 22% [95% CI 17-28%]. Trials enrolling patients with more active disease confirmed by endoscopy [endoscopy subscore ≥ 2] were associated with lower placebo rates. Conversely, placebo rates increased with increasing trial duration and number of study visits., Conclusions: Objective assessment of greater disease activity at trial entry by endoscopy lowered placebo rates, whereas increasing trial duration and more interactions with healthcare providers increased placebo rates. These findings have important implications for design and conduct of clinical trials., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To prospectively examine the association between human papilloma virus (HPV) colonization of the colonic mucosa and the development of colorectal polyps (CRPs), and colorectal cancer (CRC) in Saudi Arabia., Methods: A case control study was performed between January 2013 and December 2014. All eligible patients underwent standard diagnostic colonoscopy. Patients with polyps or colorectal cancer were considered cases, while those with any other endoscopic findings were controls. Biopsy samples from polyps and tumors, and/or from normal colonic mucosa were acquired. Human papilloma virus colonization was detected using a hybrid capture technique of samples taken from both normal tissue, and CRPs and CRC. The association between HPV and CRPs/CRC was evaluated., Results: A total of 132 patients were recruited. The mean age was 53 (± 15.9) years. Sixty patients had endoscopically detectable CRPs/CRC, and 72 had either inflammation or normal endoscopic evaluations. Only 4 (0.8%) of the 132 samples that were collected and analyzed were positive for the HPV gene. Statistical analysis did not identify any significant association between HPV colonization and the presence of CRPs/CRC. The only significant predictor of detecting CRPs/CRC on colonoscopy was symptomatic presentation (odds ratio=11.072, 95% confidence interval 4.7-26.2, p less than 0.001)., Conclusion: Human papilloma virus colonic colonization is rare in Saudi Arabia. An association between HPV colonization and CRP/CRC development could not be identified in this cohort of patients.

Background: Thyroid nodule is a common finding in the general population. Fine-needle aspiration remains a crucial step in the assessment of any thyroid nodules. The aim of this study is to compare the accuracy of needle aspiration with and without ultrasound guidance (USFNA, FNA respectively)., Methods: Retrospective chart review of 150 consecutive patients who had thyroid surgery. Fine needle aspiration biopsy, histopathology results alongside demographics and nodule sizes were recorded., Results: There was no statistical difference in the nodule size of both groups. USFNA showed a significantly higher specificity and positive predictive values compared to FNA., Conclusion: When readily available, USFNA should be considered in the investigations of a thyroid nodule.

The manifestations of schistosomiasis typically result from the host inflammatory response to parasitic eggs that are deposited in the mucosa of either the gastrointestinal tract or bladder. We present here a case of a 50-year-old gentleman with a rare gastrointestinal presentation of both schistosomal appendicitis and mesenteric thrombosis.

Background: Inflammatory bowel diseases (IBD) are a group of heterogeneous conditions, characterized by immune-mediated inflammation of the gastrointestinal tract. Traditionally, medical management of these disorders has been based on use of systemic immunosuppressives. The development of new drugs that selectively inhibit leukocyte trafficking to the gut has the potential to reduce inflammation and minimize systemic toxicities., Key Messages: In this article, we review the immunology of the gut and the mechanism of action these emerging therapies for IBD. Natalizumab, a monoclonal antibody to the α4 integrin, was approved for the treatment of multiple sclerosis and showed promise in Crohn's disease (CD), however it is encumbered by the risk of progressive multifocal leukoencephalopathy. Vedolizumab inhibits the α4β7 integrin to induce clinical remission in patients with both ulcerative colitis and CD. Long-term safety data on this agent is not yet available. We also review agents in the pipeline. Finally, we discuss the positioning of therapies and potential alterations to therapeutic algorithms as new medications emerge., Conclusions: New therapies are emerging for IBD; however, long-term data are pending. The positioning of these agents in algorithms will evolve., (© 2016 S. Karger AG, Basel.)

Objective: Histopathology is potentially an important outcome measure in UC. Multiple histological disease activity (HA) indices, including the Geboes score (GS) and modified Riley score (MRS), have been developed; however, the operating properties of these instruments are not clearly defined. We assessed the reproducibility of existing measures of HA., Design: Five experienced pathologists with GI pathology fellowship training and expertise in IBD evaluated, on three separate occasions at least two weeks apart, 49 UC colon biopsies and scored the GS, MRS and a global rating of histological severity using a 100 mm visual analogue scale (VAS). The reproducibility of each grading system and for individual instrument items was quantified by estimates of intraclass correlation coefficients (ICCs) based on two-way random effects models. Uncertainty of estimates was quantified by 95% two-sided CIs obtained using the non-parametric cluster bootstrap method. Biopsies responsible for the greatest disagreement based on the ICC estimates were identified. A consensus process was used to determine the most common sources of measurement disagreement. Recommendations for minimising disagreement were subsequently generated., Results: Intrarater ICCs (95% CIs) for the total GS, MRS and VAS scores were 0.82 (0.73 to 0.88), 0.71 (0.63 to 0.80) and 0.79 (0.72 to 0.85), respectively. Corresponding inter-rater ICCs were substantially lower: 0.56 (0.39 to 0.67), 0.48 (0.35 to 0.66) and 0.61 (0.47 to 0.72). Correlation between the GS and VAS was 0.62 and between the MRS and VAS was 0.61., Conclusions: Although 'substantial' to 'almost perfect' ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We conducted a meta-analysis of the association between leisure time physical activity (LTPA) and risk of pancreatic cancer to update previous analyses in light of newly published studies, to examine subgroups of interest and potential sources of heterogeneity. We searched the PubMed and MEDLINE databases for studies until February 2015. Study information was collected using a standardized form to abstract relevant data on study design, number of cases, participant and study characteristics, assessment of LTPA, risk estimates, and adjustments for confounding by two independent abstractors. We used random-effects models to pool estimates from included studies of lowest versus highest comparison of LTPA. The search identified 26 studies eligible for inclusion into the meta-analysis. The combined summary risk estimate was [relative risk (RR), 0.89; 95% confidence interval (CI), 0.82-0.96]. There was evidence of heterogeneity across studies (I(2) = 22.1%, Pheterogeneity = 0.130). Some of the heterogeneity could be explained by study design, with stronger protective effects observed among case-control studies (RR, 0.69; 95% CI, 0.59-0.81) compared with cohort studies (RR, 0.96; 95% CI, 0.91-1.02). Across study designs, age of population was a source of heterogeneity, with stronger effects observed among younger (<50 years) populations. The present meta-analysis supports a protective association between LTPA and pancreatic cancer with an 11% risk reduction observed. LTPA appears to have the strongest effect among young populations. Additional investigations are needed to provide insights regarding the impact of LTPA in healthy adult populations, to reduce the risk of pancreatic cancer and encourage increases in LTPA., (©2015 American Association for Cancer Research.)

Background: Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon that has a relapsing-remitting course. Health related quality of life (HRQL) is significantly lower in patients with UC than the general population due to the negative effects of the disease on physical, psychological and social well-being. Randomized controlled trials (RCTs) evaluating medical interventions for UC have traditionally used clinical disease activity indices that focus on symptoms to define primary outcomes such as clinical remission or improvement. However, this approach does not evaluate benefits that are highly relevant to patients such as HRQL OBJECTIVES: The primary objective was to assess the impact of biologic therapy on the HRQL of UC patients., Search Methods: We searched PubMed, MEDLINE, EMBASE and CENTRAL from inception to September, 2015. Conference abstracts and reference lists were also searched., Selection Criteria: RCTs that compared biologics to placebo in UC patients and reported on HRQL using the Inflammatory Bowel Disease Questionnaire (IBDQ), or the SF-36 or EQ-5D to measure HRQL were included., Data Collection and Analysis: Two authors independently screened studies for inclusion, extracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was improvement in HRQL. For dichotomous outcomes we calculated the risk ratio (RR) and 95% confidence interval (CI). For continuous outcomes we calculated the mean difference (MD) and 95% CI. The overall quality of the evidence supporting the primary outcome was assessed using GRADE., Main Results: Nine RCTs (n = 4143) were included. Biologics included rituximab (one small study), interferon-ß-1a (one study), vedolizumab (one study), and the tumor necrosis factor-alpha (TNF-α) antagonists infliximab (two studies), adalimumab (three studies), and golimumab (one study). Risk of bias was low in eight studies. The rituximab study was judged to be at high risk of bias due to attrition bias. The studies comparing interferon-ß-1a and rituximab to placebo found no clear evidence of a difference in the proportion of patients who experienced an improvement in HRQL at 8 or 12 weeks respectively. The proportion of patients with a clinically meaningful improvement in HRQL at 6 or 52 weeks was significantly higher in vedolizumab patients compared to placebo. At 6 weeks 37% (83/225) of vedolizumab patients had an improvement in IBDQ score of at least 16 points from baseline compared to 23% (34/149) of placebo patients (RR 1.62, 95% CI 1.15 to 2.27; 1 study). At 52 weeks, 64% (157/247) of vedolizumab patients had an improvement in IBDQ score of at least 16 points from baseline compared to 38% (48/126) of placebo patients (RR 1.62, 95% CI 1.15 to 2.27; 1 study). A GRADE analysis indicated that the overall quality of the evidence supporting these outcomes was moderate due to sparse data (< 400 events). Patients who received maintenance vedolizumab every eight weeks had significantly higher mean SF-36 scores than placebo patients at 52 weeks (MD 3.40, 95% CI 1.56 to 5.24, 1 study 248 patients). This difference appears to be clinically meaningful as the lower boundary for a clinically meaningful change in SF-36 is three points. A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (< 400 events). Adalimumab patients had significantly higher mean IBDQ scores than placebo patients at weeks 8 (MD 9.00, 95% CI 2.65 to 15.35; 1 study, 494 patients) and 52 (MD 8.00, 95% CI 0.68 to 15.32; 1 study, 494 patients). However, these differences may not be clinically meaningful as the lower boundary for a clinically meaningful change in IBDQ is 16 points. A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (< 400 events). Golimumab patients who received a dose of 200/100 mg (MD 12.20, 95% CI 6.52 to 17.88; 504 patients) or 400/200 mg (MD 12.10, 95% CI 6.40 to 17.80; 508 patients) had significantly higher mean IBDQ scores than placebo patients at week 6. Although a GRADE analysis indicated that the overall quality of the evidence supporting these outcomes was high, the difference in IBDQ scores may not be clinically meaningful. Infliximab patients had significantly higher mean IBDQ scores at week 6 or 8 than placebo patients (MD 18,58, 95% CI 13.19 to 23.97; 2 studies, 529 patients). This difference in HRQL is clinically meaningful. A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was high. The proportion of patients with a clinically meaningful improvement in HRQL at eight weeks was significantly higher in infliximab patients compared to placebo. Sixty-nine per cent (333/484) of infliximab patients had an improvement in IBDQ score of > 16 points from baseline compared to 50% of placebo patients (RR 1.39, 95% CI 1.21 to 1.60; 1 study). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was high. Similar results were found between infliximab and placebo when HRQL was measured using the SF-36 instrument. One small study (n = 43) found no difference in HRQL between infliximab and placebo when measured by the EQ-5D. Pooled analyses of TNF-α antagonists showed a benefit in HRQL favouring TNF-α over placebo., Authors' Conclusions: These results suggest that biologics have the potential to improve HRQL in UC patients. High quality evidence suggests that infliximab provides a clinically meaningful improvement in HRQL in UC patients receiving induction therapy. Moderate quality evidence suggests that vedolizumab provides a clinically meaningful improvement in HRQL in UC patients receiving maintenance therapy. These findings are important since there is a paucity of effective drugs for the treatment of UC that have the potential to both decrease disease activity and improve HRQL. More research is needed to assess the long-term effect of biologic therapy on HRQL in patients with UC. More research is needed to assess the impact of golimumab and adalimumab on HRQL in UC patients. Trials involving direct head to head comparisons of biologics would help determine which biologics provide optimum benefit for HRQL.

The objective of this position statement from the Saudi Gastroenterology Association is to guide gastroenterologists on the use of tumor necrosis factor-alfa (TNF-α) antagonists for the treatment of the idiopathic inflammatory bowel diseases, Crohn's disease, and ulcerative colitis. In this article, we summarize the relevant literature regarding the safety and efficacy of TNF-α antagonists, highlight relevant safety concerns specific to the environment in Saudi Arabia, and provide specific recommendations for the use of these agents.

Objectives: Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress subclinical inflammation has emerged as a treatment concept. As endoscopic monitoring is invasive and resource intensive, identification of valid markers of disease activity is a priority. The objective was to evaluate the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD., Methods: Databases were searched from inception to November 6, 2014 for relevant cohort and case-control studies that evaluated the diagnostic accuracy of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms consistent with active IBD. Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis., Results: Nineteen studies (n=2499 patients) were eligible. The pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95% confidence interval (CI) 0.34-0.64) and 0.92 (95% CI 0.72-0.96), 0.88 (95% CI 0.84-0.90) and 0.73 (95% CI 0.66-0.79), and 0.82 (95% CI 0.73-0.88) and 0.79 (95% CI 0.62-0.89), respectively. FC was more sensitive than CRP in both diseases and was more sensitive in ulcerative colitis than Crohn's disease., Conclusions: Although CRP, FC, and SL are useful biomarkers, their value in managing individual patients must be considered in specific clinical contexts.

Background: We performed a systematic review to evaluate the efficacy and safety of vedolizumab for induction and maintenance of remission in ulcerative colitis., Methods: A literature search to June 2014 identified all applicable randomized trials. Outcome measures were clinical and endoscopic remission, clinical and endoscopic response, quality of life, and adverse events. The risk ratio (RR) and 95% confidence intervals (CI) were estimated for each outcome. Study quality was evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to assess the quality of the evidence., Main Results: Four studies (606 patients) were included. The risk of bias was low. Pooled analyses indicated that vedolizumab was significantly superior to placebo for induction of remission (RR = 0.86, 95% CI, 0.80-0.91), clinical response (RR = 0.82, 95% CI, 0.75-0.91), endoscopic remission (RR = 0.82, 95% CI, 0.75-0.91), and for achieving remission at 52 weeks in week 6 responders (RR = 2.73, 95% CI, 1.78-4.18). GRADE analyses suggested that the overall quality of the evidence was high for induction of remission and moderate for maintenance therapy (due to sparse data consisting of 246 events). No statistically significant difference was observed in the incidence of adverse events between vedolizumab and placebo., Conclusions: Vedolizumab is superior to placebo as induction and maintenance therapy for ulcerative colitis. Future studies are needed to define long-term efficacy and safety of this agent.

Background/aims: Success of colorectal cancer (CRC) screening is dependent in part on the proportion of uptake by the targeted population. We aimed in this study to identify factors that were associated with willingness to undergo CRC screening based on the health belief model (HBM)., Patients and Methods: This was a cross-sectional study among citizens of Riyadh, Saudi Arabia. Demographic data collected included gender, age, education, marital status, employment status, a history of CRC in the family or knowing a friend with CRC, as well as income. A questionnaire was developed in Arabic based on the HBM and included enquiries on knowledge about CRC symptoms and risk factors, types of CRC screening tests, perceived risk of CRC, previously undergoing CRC screening, intent to undergo CRC screening, perceived barriers to CRC screening, perceived severity of CRC, as well as attitudes toward CRC and its screening., Results: Five hundred participants were included. The mean age was 41.0 years (SD 10.7). Males were 50% and only 6.7% of those between 50 and 55 years of age had undergone CRC screening. Of those surveyed, 70.7% were willing to undergo CRC screening. Also, 70.5% thought that CRC is curable, 73.3% believed it was preventable, whereas 56.7% thought it was a fatal disease. Neither gender, level of education, occupation, income, marital status, nor general knowledge about CRC was found to be associated with the willingness to undergo CRC screening. Recognizing that colonoscopy was a screening test (OR 1.55, 95% CI; 1.04-2.29) was associated with a strong desire to undergo CRC screening while choosing a stool-based test was associated with not willing to undergo CRC screening (OR 0.59, 95%CI; 0.38-0.91)., Conclusion: We found that the majority of those interviewed were willing to undergo CRC screening and identified a number of barriers as well as potential areas that could be targeted in the promotion of CRC screening uptake if such a national program were to be implemented.

Introduction: Crohn's disease (CD) is an idiopathic inflammatory disorder of the gastrointestinal tract traditionally treated by the step-wise use of corticosteroids, antimetabolites and TNF-α antagonists. However, recent evidence indicates that the early introduction of drug combinations might be a superior strategy to step-care., Areas Covered: In this article, we review existing literature regarding the efficacy and safety of combination drug therapy for the management of CD. Five major databases: MEDLINE, EMBASE, PubMed, the Cochrane Library (CENTRAL) and DDW abstracts were electronically searched from inception to February 2015 for any relevant studies., Expert Opinion: Existing data strongly support the use of combination therapy for CD. The benefit of this approach appears to outweigh any associated risks. Until the role of gut selective therapies are better established, combination therapy should be considered the standard treatment approach for CD.

Since the cause of inflammatory bowel disease (IBD) is unknown, therapy has traditionally been based on the empiric use of anti-inflammatory drugs. However, the recent identification of specific mechanisms that regulate cellular migration into inflamed intestinal tissue has provided novel targets for drug development. In this article, we discuss these mechanisms and review emerging safety and efficacy data regarding use of selective inhibitors of leukocyte trafficking for the treatment of IBD., (© 2015 S. Karger AG, Basel.)