Differences in the Adverse Event Burden of Corticosteroid Use in Inflammatory Bowel Disease as Reported Between Adverse Event Reporting Systems and a Patient Questionnaire.

BACKGROUND AND AIMS: Corticosteroids are widely used in managing inflammatory bowel disease [IBD]. While adverse events [AEs] of corticosteroids are well recognised, current understanding of corticosteroid-related AE burden in IBD remains incomplete. METHODS: AE reports for prednisone/prednisolone and budesonide were extracted from the Food and Drug Administration Adverse Event Reporting System [FAERS] and VigiBase databases. Total and frequently reported AEs were tabulated, and AEs of special interest were compared with reports for all drugs using proportional reporting ratio criteria. Database reports were compared with AEs reported in a patient survey capturing corticosteroid exposure and AE recall. RESULTS: In FAERS and VigiBase, 344,140 and 42,836 AEs were reported, respectively, in patients with IBD; among these, 10,157 [3.0%] and 11,391 [26.6%], respectively, were related to prednisone/prednisolone or budesonide. AEs associated with corticosteroid use in IBD increased over time. Adrenal insufficiency, Cushingoid complications, osteonecrosis, osteoporosis, diabetes and pancreatitis were disproportionately reported for corticosteroids. Among 9229 patients who responded to the survey, 6434 [69.7%] reported corticosteroid exposure. AEs were more frequently recalled by patients exposed to prednisone [61.9%] vs budesonide [27.4%; p = 0.0001]. The most commonly recalled AEs differed from those reported in the pharmacovigilance databases and included weight gain, sleep problems, mood disturbance and skin changes. Younger patients and those with mental health disorders were more likely to recall suicidal thoughts/attempts. CONCLUSIONS: AEs associated with IBD-related corticosteroid use were frequent. Patients reported AEs affecting quality of life, while clinicians disproportionately reported AEs based on objective diagnostic criteria.

Biologic therapy for inflammatory bowel disease: Real-world comparative effectiveness and impact of drug sequencing in 13,222 patients within the UK IBD BioResource.

BACKGROUND AND AIMS: To compare effectiveness of different biologic therapies and sequences in patients with Inflammatory Bowel Disease (IBD) using real-world data from a large cohort with long exposure. METHODS: Demographic, disease, treatment and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups. RESULTS: 13,222 evaluable patients received at least one biologic. In ulcerative colitis (UC) first line vedolizumab (VDZ) demonstrated superior effectiveness over five years compared to anti-TNF agents (p=0.006). VDZ was superior to both infliximab (IFX) and adalimumab (ADA) after ADA and IFX failure respectively (p<0.001 and p<0.001). Anti-TNF therapy showed similar effectiveness when used first-line, or after failure of VDZ. In Crohn's disease (CD) we found significant differences between first line treatments over ten years (p=0.045), with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first line anti-TNF failure in CD (p=0.035). Patients with UC or CD experiencing TNF-failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF. CONCLUSIONS: We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF.

Methotrexate in inflammatory bowel disease: A primer for gastroenterologists.

Methotrexate is an antineoplastic agent that is also used at lower doses for anti-inflammatory properties. Along with thiopurines (azathioprine and 6-mercaptopurine), it has historically been an important part of pharmacological treatment for patients with inflammatory bowel disease. Despite an increase in therapeutic options, these immunomodulators continue to play important roles in the management of inflammatory bowel disease, used either as a monotherapy in mild to moderate cases or in combination with monoclonal antibodies to prevent immunogenicity and maintain efficacy. In light of data linking the use of thiopurines with the risk of malignancies, methotrexate has regained attention as a potential alternative. In this article, we review data on the pharmacology, safety, and efficacy of methotrexate and discuss options for the positioning of methotrexate alone, or in combination, in therapeutic algorithms for Crohn's disease and ulcerative colitis.

Undisclosed payments by pharmaceutical manufacturers to authors of inflammatory bowel disease guidelines in the United States.

BACKGROUND: Payments from pharmaceutical drug manufacturers to authors of clinical practice guidelines (CPGs) may have an impact on their recommendations. In this study, we aimed to evaluate the accuracy of financial conflict of interest (FCOI) declarations among authors of Inflammatory Bowel Disease (IBD) guidelines. METHODS: We collected data on industry payments to authors of IBD guidelines published by the American Gastroenterology Association (AGA), American College of Gastroenterology (ACG) and American Society of Gastrointestinal Endoscopy (ASGE). We reported the accuracy of the authors' declarations by comparing their statements in the FCOI section of the guidelines with the data reported on the Centers for Medicare and Medicaid Services website (CMS-OP). We also investigated the adherence of IBD guidelines to the National Academy of Medicine (NAM) criteria for trustworthy guidelines. RESULTS: A total of eight clinical practice guidelines and 35 individual authors were included. Four authors had no profile identified at CMS-OP. The total payment to all included authors was $10,575,843.06, with a mean payment of $314,242.38 per author. A total of 28/35 authors (80%) received payment from pharmaceutical companies, 23/35 (65.7%) received $10,000 or more, 15/35 (42.8%) received $100,000 or more and 3/35 (8.57%) received $1,000,000 or more. Total discrepancies identified while comparing the authors' declaration of their FCOI and CMS-OP were 28: ACG had 12/14 (85.7%), AGA had 7/12 (53.8%) and ASGE had 9/10 (90%) discrepancies. None of the guidelines met all NAM criteria and 4/8 (50%) guidelines met none. CONCLUSIONS: Discrepancies exist between authors' declarations in the FOCI section and data on CMS-OP. Poor compliance with the NAM criteria was prevalent among authors of IBD guidelines. More transparency in reporting and monitoring is needed.

Idiopathic Myointimal Hyperplasia of Mesenteric Veins (IMHMV) with two spontaneous bowel perforations: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is a poorly understood disorder which poses a diagnostic challenge to clinicians and pathologists. Here we have described the case of a male patient with IMHMV along with a presumed history of ulcerative colitis for 1 year. CASE PRESENTATION: A 55-year-old male presented to the OPD with history of chronic abdominal pain. Clinical and radiological examination coupled with endoscopic findings resulted in the patient being wrongly diagnosed to be a case of ulcerative colitis and was managed accordingly. Throughout his multiple hospital visits following treatment for ulcerative colitis, the patient was persistently symptomatic. He presented with 10 days history of increasing abdominal pain and constipation following which he developed spontaneous colonic perforation for which he underwent exploratory laparotomy left colectomy and Hartman's procedure. The final pathology of the resected colon found to be consistent of Idiopathic myointimal hyperplasia of the mesenteric veins and ischemic bowel changes. CLINICAL DISCUSSION: The absence of clear-cut endoscopic biopsy findings of ulcerative colitis made radiological picture to be the mainstay for diagnosis, which was inaccurate and exposed the patient to unnecessary treatment with immuno-modulators thus resulting in poor response to treatment. As the disease progressed, further narrowing of the vessels made the clinical picture to look closer to ischemic bowel pathology as the patient developed a top surgical emergency (i.e. bowel perforation). Such pathological finding (IMHMV) can only be diagnosed in a fully prepared tissue histology, but rather be considered when no other consistent alternative diagnosis was found. CONCLUSION: The treating physicians must definitely consider the possibility of idiopathic myointimal hyperplasia of mesenteric veins when similar manifestations are encountered in biopsy specimens of old cases with suspected inflammatory bowel disease or non-occlusive ischemia of the distal colorectum.

Barriers to research productivity among gastroenterologists and hepatologists in Saudi Arabia.

BACKGROUND: Clinical research is essential for the advancement of medical knowledge and evidence-based medical practice. In this study, we aimed to identify barriers that limit research productivity among gastroenterologists in Saudi Arabia. METHODS: We conducted a national online survey targeting gastroenterologists in Saudi Arabia. Participants were asked about the patterns of their practice, their prior research activities, and potential barriers to research productivity. Univariate and multivariate analyses were performed to examine the association between different factors and research productivity. RESULTS: A total of 85 gastroenterologists completed the survey. Respondents were predominantly male physicians (90.6%) and 40% of them belonged to the age group of 40-49 years. About 85.9% had at least one prior research participation of any type. Around 67.1% of the respondents had been a primary investigator at least once in the last 5 years, while only 23.5% had been a primary investigator at a minimum average rate of once a year. Multiple barriers to research productivity were identified: insufficient research time (78.8%), lack of funding and compensation (77.6%), lack of a statistician (68.2%), insufficient research training (64.7%), lack of connection (60%), lack of technical support (57.6%), and lack of interest (31%). On univariate analysis, insufficient research time and lack of funding and compensation were significantly associated with no research participation (P <0.01 and 0.03, respectively). On multivariate analysis, lack of funding and compensation was independently associated with no research participation (adjusted OR 15.32;95% C.I 2.66, 121.58, P < 0.01). CONCLUSIONS: Barriers to research productivity are highly prevalent among gastroenterologists in Saudi Arabia. Insufficient research time and lack of funding and compensation are the most common. Interventions are needed to promote research activities.

The Prevalence of Irritable Bowel Syndrome Among Board-Certified Medical Doctors In Saudi Arabia: A Cross-sectional Study.

INTRODUCTION: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. A pooled analysis showed a global prevalence of 11.2%. Few studies looked at the prevalence of IBS in health care providers. The aim of this study was to determine the prevalence of IBS among board-certified physicians and surgeons. METHODS: Board-certified physicians and surgeons in Saudi Arabia were invited to complete a web-based survey. It included questions regarding participant demographics, specialty, practice type and hours worked per week. The Rome IV-validated questionnaire was used to identify subjects with IBS. The primary outcome of the study was the prevalence of IBS among physicians. Secondary outcomes included exploring the effect on IBS prevalence of age, gender, marital status, work hours, specialty, gastroenterology subspecialty and working in a public versus private hospital. RESULTS: The final analysis included 594 subjects, with 419 males and a median age of 41. The vast majority (86%) were married. Nearly 90% worked in a public hospital exclusively, and the median number of hours worked per week was 48. The overall prevalence of IBS was 16.3%. In a binary logistic regression model, age (odds ratio [OR] = 0.931, P < 0.0001), gender (OR = 0.504, P = 0.003) and work hours (OR = 2.397, P < 0.0001) significantly predicted the presence of IBS. Marital status and specialty did not predict IBS prevalence. DISCUSSION: This cross-sectional study shows that the prevalence of IBS among physicians in Saudi Arabia to be 16.3%. IBS was more common in females, those who worked longer hours and younger physicians. There was no association between practicing certain specialties and IBS. However, the lack of difference in our cohort may be attributed to the relatively small sample size from each specialty.

A cross-sectional survey on the psychological impact of the COVID-19 pandemic on inflammatory bowel disease patients in Saudi Arabia.

Background/Aims: The coronavirus (COVID-19) pandemic has caused significant disruption to patients with chronic illnesses. We explored the emotional state, perception, and concerns of Saudi patients with inflammatory bowel disease (IBD) during the crisis. Materials and Methods: We conducted a cross-sectional survey from 30 March to 5 April, 2020 using a pre-designed questionnaire distributed through social media platforms to IBD patients. The five-part questionnaire included an assessment of psychological wellbeing using a previously validated Arabic version of the Hospital Anxiety and Depression Scale (HADS), which includes domains for anxiety (HADS-A) and depression (HADS-D). A logistic regression analysis was used to uncover possible associations between patient characteristics and anxiety and depression. Results: The data from 1156 IBD patients were analyzed. Normal, borderline, and HADS-A scores consistent with a diagnosis of anxiety were reported by 423 (36.6%), 174 (15.1%), and 559 (48.4%) patients, respectively. However, 635 (69%) patients had normal scores and 273 (30.1%) had borderline HADS-D scores; no patients reported scores consistent with depression. Based on a multiple logistic regression analysis, patients educated till a high school diploma (OR = 2.57, 95% CI: 0.09-6.05, P = 0.03) and that had indeterminate colitis (OR = 2.23, 95% CI: 1.27-3.89, P = 0.005) were more likely to express anxiety. Conclusions: Many patients expressed symptoms of anxiety, although not depression. Female patients, patients educated till a high school diploma, and those with indeterminate colitis were more likely to have anxiety. IBD patients require greater attention during a pandemic to avoid adverse disease-related outcomes.

Risk of neutropenia in inflammatory bowel disease patients treated with TNF inhibitors: A single-center, retrospective cohort study.

BACKGROUND/AIM: Tumor necrosis factor inhibitors (TNFi) have become the mainstay of treatment in moderate-to-severe cases of inflammatory bowel disease (IBD). Neutropenia has been reported in patients receiving TNFi for IBD and other diseases. In this study, we aimed to ascertain the relationship between the use of TNFi and the development of neutropenia in patients with IBD. PATIENTS AND METHODS: This is a retrospective cohort study including all adult patients with IBD receiving TNFi at a tertiary care center over an 11-year period. The primary outcome was the development of any neutropenic episode after starting a TNFi. For our secondary outcomes, we evaluated the impact of concomitant use of 5-aminosalicylic acid (5-ASA) or an immunomodulator on the risk of developing neutropenia. RESULTS: The final analysis included 281 patients. Of those included, 34.2% developed at least one episode of neutropenia while on a TNFi. The majority of these episodes (67.7%) were mild with ANC between 1000 and 1500/mm3. No significant difference was observed in the age, gender, agent used or type of IBD between those who developed neutropenia and those who did not. Concomitant use of azathioprine (OR = 2.32, 95% CI: 1.26-4.28; P = 0.007) or 5-ASA (OR = 3.15, 95% CI: 1.55-6.39; P = 0.001) were significant independent predictors of developing neutropenia. CONCLUSIONS: In this study, mild neutropenia was common among patients with IBD on TNFi. Future prospective studies are required to further clarify the significance of neutropenia in patients with IBD receiving TNFi.

The psychological impact of COVID-19 pandemic on physicians in Saudi Arabia: A cross-sectional study.

Background/Aim: COVID-19 pandemic exposed physicians to extraordinary stress and made them vulnerable to various types of psychological illnesses. The aim of this study was to evaluate the impact that the COVID-19 pandemic had on the psychological well-being of physicians. Materials and Methods: We performed a cross-sectional, survey-based study, targeting physicians in Saudi Arabia during the COVID-19 pandemic. The primary outcome was to assess the psychological impact that the pandemic had on physicians by using a questionnaire that was previously designed and used by Reynold's et al. to survey Canadians during the SARS outbreak in 2003. The questionnaire assessed respondents' understanding of the rationale for quarantine, quarantine behaviors (including difficulties and compliance), as well as socio-economic and psychological impacts through answers that are based on a Likert scale. We also assessed the possible risk factors for psychological disorders related to the pandemic. Results: The study included 529 physicians from various regions in Saudi Arabia. The enrolled physicians were practicing different specialties and branches in medicine. We classified them based on their workplace in relation to COVID-19 exposure to: COVID-19 designated center vs. non-COVID-19 designated centers. Furthermore, we subdivided the physicians who work in COVID-19 designated centers to those who work in high-risk areas such as ER, ICU and COVID-19 isolation wards and other areas as low-risk areas. The most common feelings reported by the physicians during the pandemic were: worry (357, 67.5%), isolation (301, 56.9%) and fear (263, 49.7%). According to logistic regression analysis, physicians older than age 60 were less likely to feel isolated (OR = 0.08, 95% CI = 0.01-0.96, P = 0.05), female physicians were more likely to experience fear (OR = 2.96, 95% CI = 1.20 - 7.27, P = 0.02) and worry (OR = 2.87,95% CI = 1.23 - 6.69, P = 0.02), while physicians with a previous exposure to similar traumatic events were less likely to experience fear (OR = 0.24, 0.10 - 0.64, P = 0.004) during the COVID-19 pandemic. Conclusions: The COVID-19 pandemic had a negative psychological effect on physicians in Saudi Arabia. Gender, age, and previous exposure to similar traumatic events were predictive of psychological reactions to the pandemic in this population.

Biosimilars to Antitumor Necrosis Factor Agents in Inflammatory Bowel Disease.

Anti- tumor Necrosis Factor (anti-TNF) agents are the backbone treatment of moderate to severe cases of inflammatory bowel disease. One of the main drawbacks of these agents is the high cost. The introduction of biosimilar products to anti-TNF agents is expected to lower the cost. Health care providers ought to be aware of the available data that addresses the safety and efficacy of biosimilars in IBD patients. This article outlines the current evidence-based data regarding the available biosimilar products, their safety, efficacy and how to deal with patients' concerns.