Attitudes, perceptions and barriers in implementing therapeutic drug monitoring for anti-TNFs in inflammatory bowel disease: a survey from the Middle East.

Background: A growing body of evidence underscores the beneficial impact of therapeutic drug monitoring (TDM) on the efficacy and cost-effectiveness of anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD). Objectives: We surveyed clinician attitudes, perceptions and barriers related to TDM in IBD in the Middle East. Design: A 15-question survey was distributed through national gastroenterological societies in five Middle Eastern countries (UAE, Saudi Arabia, Kuwait, Lebanon and Egypt). Methods: Data on clinician characteristics, demographics, utilization patterns and obstacles related to the adoption of TDM with anti-TNFs were gathered. Logistic regression analysis was used to predict factors influencing the utilization of TDM. Results: Among 211 respondents (82% male), 82% were consultants, 8% were physicians with an interest in gastroenterology (GI), and 6% were GI trainees. Of these, 152 met inclusion criteria, treating >5 IBD patients per month and ⩾1 with an anti-TNF per month. TDM was used in clinical practice by 78% (95% CI: 71-85) of respondents. TDM was utilized following the loss of response (LOR) in 93%, for primary non-response (PNR) in 40% and before restarting anti-TNF therapy after a drug holiday in 33% of respondents, while 34% used TDM proactively. No specific factors were associated with the use of TDM. Barriers to TDM use included cost (85%), time lag to results (71%) and lack of insurance reimbursement (65%). Overall knowledge of TDM (70%), interpretation and actioning of results (76%) or awareness of clinical guidelines (57%) were not perceived as barriers. If barriers were removed, 95% would use TDM more frequently; 93% for LOR, 60% for PNR, 50% when restarting after a drug holiday, and 54% would use TDM proactively. Conclusion: Most gastroenterologists use TDM for LOR, with cost, time lag and insurance reimbursement being significant barriers. Addressing these barriers would increase the judicious use of reactive and proactive TDM to optimize anti-TNF therapy in IBD.

Attitudes, perceptions, and barriers in implementing therapeutic drug monitoring for anti-TNFs in inflammatory bowel disease: a survey from Middle East Anti-TNF therapies are perhaps the most widely used and available biological therapies for the treatment of inflammatory bowel disease globally even though other agents have been licensed in recent years. The role of therapeutic drug monitoring to optimise outcomes and mitigate against immunogenicity with anti-TNF agents are now being appreciated. Our study investigates clinician attitudes, perceptions, and barriers related to therapeutic drug monitoring (TDM) in the context of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD) through a comprehensive survey distributed from five Middle Eastern countries. Among 211 respondents (82% male), 82% were consultants, 8% physicians with an interest in gastroenterology (GI), and 6% GI trainees. TDM was utilised following loss of response (LOR) in 93%, for primary non-response (PNR) in 40%, and before restarting anti-TNF therapy after a drug holiday by 33% of respondents, while 34% used TDM proactively. No specific factors were associated with the use of TDM. Barriers to TDM use included cost (85%), time lag to result (71%), and lack of insurance reimbursement (65%). Overall knowledge of TDM (70%), interpretation and actioning of results (76%), or awareness of clinical guidelines (57%) were not perceived as barriers. If barriers were removed, 95% would use TDM more frequently; 93% for LOR, 60% for PNR, 50% when restarting after a drug holiday and 54% would use TDM proactively. Most gastroenterologists use TDM for LOR, with cost, time lag, and insurance reimbursement being significant barriers. Addressing these barriers would increase judicious use of reactive and proactive TDM to optimise anti-TNF therapy in IBD.

The views of African and Middle Eastern Gastroenterologists on the management of mild-to-moderate, non-erosive gastro-esophageal reflux disease (GERD).

INTRODUCTION: Gastro-esophageal reflux disease (GERD) is a common gastrointestinal disorder that occurs when backflow of the gastric contents into the esophagus results in troublesome symptoms. Though GERD has been extensively studied in Western populations, literature on the management of GERD in patients in Africa and Middle East (AME) is scarce. AREAS COVERED: In this review, we provide an overview of the management of mild-to-moderate GERD in AME. Here we focus on the efficacy and safety of currently available treatments for GERD to help physicians and community pharmacists appropriately manage patients with mild-to-moderate GERD in the primary healthcare setting, detailing specific situations and patient scenarios that are relevant to the region, including management of GERD during Ramadan and post-bariatric surgery. EXPERT OPINION: Under-appreciation of the burden of GERD in the region has resulted in a lack of consensus on management. Barriers that currently prevent the adoption of treatment guidelines in the primary healthcare setting may include lack of availability of local guidelines and referral systems, a paucity of region-specific research, and dogmatic adherence to traditional practice. By increasing awareness, strengthening knowledge, and by more effective utilization of resources, physicians and pharmacists could optimize GERD management strategies to better support patients.

Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

Modelling the benefits of an optimised treatment strategy for 5-ASA in mild-to-moderate ulcerative colitis.

OBJECTIVES: 5-aminosalicylate (mesalazine; 5-ASA) is an established first-line treatment for mild-to-moderate ulcerative colitis (UC). This study aimed to model the benefits of optimising 5-ASA therapy. METHODS: A decision tree model followed 10 000 newly diagnosed patients with mild-to-moderately active UC through induction and 1 year of maintenance treatment. Optimised treatment (maximising dose of 5-ASA and use of combined oral and rectal therapy before treatment escalation) was compared with standard treatment (standard doses of 5-ASA without optimisation). Modelled data were derived from published meta-analyses. The primary outcomes were patient numbers achieving and maintaining remission, with an analysis of treatment costs for each strategy conducted as a secondary outcome (using UK reference costs). RESULTS: During induction, there was a 39% increase in patients achieving remission through the optimised pathway without requiring systemic steroids and/or biologics (6565 vs 4725 for standard). Potential steroidal/biological adverse events avoided included: seven venous thromboembolisms and eight serious infections. Out of the 6565 patients entering maintenance following successful induction on 5-ASA, there was a 21% reduction in relapses when optimised (1830 vs 2311 for standard). This translated into 297 patients avoiding further systemic steroids and 214 biologics. Optimisation led to an average net saving of £272 per patient entering the model for the induction and maintenance of remission over 1 year. CONCLUSION: Modelling suggests that optimising 5-ASA therapy (both the inclusion of rectal 5-ASA into a combined oral and rectal regimen and maximisation of 5-ASA dose) has clinical and cost benefits that supports wider adoption in clinical practice.

International consensus on the prevention of venous and arterial thrombotic events in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous and arterial thrombotic events in patients with IBD. A virtual meeting took place in May 2020 involving 14 international IBD experts and 3 thrombosis experts from 12 countries. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75% of participants voting as 'fully agree' or 'mostly agree' with each statement. For each statement, the level of evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system. Consensus was reached for 19 statements. Patients with IBD harbour an increased risk of venous and arterial thrombotic events. Thromboprophylaxis is indicated during hospitalization of any cause in patients with IBD. Disease activity is a modifiable risk factor in patients with IBD, and physicians should aim to achieve deep remission to reduce the risk. Exposure to steroids should be limited. Antitumour necrosis factor agents might be associated with a reduced risk of thrombotic events.

Narrow band imaging for detection of gastric intestinal metaplasia and dysplasia: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Gastric intestinal metaplasia (GIM), a precursor of gastric adenocarcinoma, is challenging to diagnose with white light endoscopy (WLE) and can be missed by random gastric biopsies. Narrowband imaging (NBI) may potentially improve the detection of GIM. However, pooled estimates from prospective studies are lacking. METHODS: Electronic databases were searched for studies comparing NBI and WLE alone for detection of GIM and synchronous dysplasia. Primary outcome was pooled detection rate of GIM by NBI compared with WLE in prospective studies. The secondary outcome was concurrent dysplasia detection. RESULTS: Ten studies were found eligible from 306 articles screened. Eight prospective studies were found eligible for primary endpoint of GIM detection. Two other retrospective studies were included for dysplasia detection. A total of 1366 subjects (694 males, 54.4 ± 5.08 years) underwent upper endoscopy. GIM was detected in 482 (35.3%) subjects. NBI detected GIM in 32% additional subjects (70% vs 38%, RR 1.79; 95% CI 1.34-2.37; P < 0.01). Subgroup analysis revealed newer NBI scopes (GIF260) detected significantly more GIM than WLE (RR 2.47; 95% CI 1.63-3.76; P < 0.01) but not the older (H180) NBI endoscopes (RR 1.33; 95% CI 0.93-1.88; P = 0.11). There was moderate heterogeneity between the studies (I2  = 63%). In five studies (n = 628) that reported dysplasia, there was no significant difference between NBI and WLE in dysplasia detection (RR 1.09; 95% CI 0.81-1.47; P = 0.58). CONCLUSION: Narrowband imaging can significantly increase the detection of GIM when used in addition to standard white light exam during an upper endoscopy.

Cost analysis and outcome of endoscopic submucosal dissection for colorectal lesions in an outpatient setting.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD), a minimally invasive treatment for early gastrointestinal (GI) cancer, is considered challenging and risky in the colorectum. As such, most patients undergoing ESD are hospitalized due to the perceived increased risk of adverse events. The aim of this study was to compare the costs, safety and efficacy of colorectal-ESD in an outpatient vs inpatient setting in a tertiary level center. METHODS: This is a retrospective study on consecutive patients admitted for colorectal-ESD. Patients were divided into outpatients (Group-A, same-day discharge), and inpatients (Group-B, admitted for at least one night). Data on overall costs, outcomes and adverse events were assessed for each group. RESULTS: A total of 136 patients were considered. Fourteen were excluded because ESD was not performed due to intraprocedural suspicion of invasive cancer. Eighty-three patients were treated as outpatients (Group-A, 68%) and 39 (Group-B, 32%) were hospitalized. R0-rate was 90.4% in Group-A and 89.7% in Group-B(P = 0.98). One perforation occurred in Group-A (1.2%) and 2 in Group-B(5.1%, P = 0.2). Mean Length of stay (LOS) was 1 day for outpatients and 3.3 days for inpatients. Management of Group-A as outpatients produced a cost savings of 941€ on average per patient. CONCLUSIONS: Outpatient colorectal-ESD is a feasible, cost-effective strategy to manage superficial colorectal tumors with outcomes comparable to inpatient colorectal-ESD. By using proper selection criteria, outpatient ESD could be considered the first-line approach for most patients.

Endoscopic Management of Benign Esophageal Ruptures and Leaks.

OPINION STATEMENT: Esophageal leaks (EL) and ruptures (ER) are rare conditions associated with a high risk of mortality and morbidity. Historically, EL and ER have been surgically treated, but current treatment options also include conservative management and endoscopy. Over the last decades, interventional endoscopy has evolved as an effective and less invasive alternative to primary surgery in these cases. A variety of techniques are currently available to re-establish the continuity of the digestive tract, prevent or treat infection related to the leak/rupture, prevent further contamination, drain potential collections, and provide nutritional support. Endoscopic options include clips, both through the scope (TTS) and over the scope (OTS), stent placement, vacuum therapy, tissue adhesive, and endoscopic suturing techniques. Theoretically, all of these can be used alone or with a multimodality approach. Endoscopic therapy should be combined with medical therapy but also with percutaneous drainage of collections, where present. There is robust evidence suggesting that this change of therapeutic paradigm in the form of endoscopic therapy is associated with improved outcome, better quality of life, and shortened length of hospital stay. Moreover, recent European guidelines on endoscopic management of iatrogenic perforation have strengthened and to some degree regulated and redefined the role of endoscopy in the management of conditions where there is a breach in the continuity of the GI wall. Certainly, due to the complexity of these conditions and the variety of available treatment options, a multidisciplinary approach is strongly recommended, with close clinical monitoring (by endoscopists, surgeons, and intensive care physicians) and special attention to signs of sepsis, which can lead to the need for urgent surgical management. This review article will critically discuss the literature regarding endoscopic modalities for esophageal leak and perforation management and attempt to place them in perspective for the physician.

Gastric Perforation following Intragastric Balloon Insertion: Combined Endoscopic and Laparoscopic Approach for Management: Case Series and Review of Literature.

BACKGROUND: Obesity is a serious disease, with substantial morbidity and mortality. The endoscopic placement of an intragastric balloon (IGB) in association with a low-calorie diet is an option for the treatment of obesity. IGB complications include dislocation of the balloon causing intestinal obstruction, upper gastro-intestinal bleeding and perforation, especially during balloon insertion or removal. Our work aims at decreasing the morbidity of open laparotomy in the management of such gastric perforations. METHODS: We report three cases of gastric perforation following IGB insertion that needed surgical intervention. Decision was made to treat them with a minimally invasive combined endoscopic and laparoscopic approach to decrease postoperative morbidity. RESULTS: All patients were successfully treated by a minimally invasive approach with less morbidity than the conventional open laparotomy. CONCLUSION: Gastric perforation should be suspected in any patient with IGB who presents with an acute abdomen. This can be managed with a minimal invasive approach.

The prevalence and importance of crypt apoptosis, focal active cryptitis, and neutrophilic infiltrate of the lamina propria in colorectal adenomas.

Even though apoptotic bodies (ABs) are frequent in colorectal adenomas, their relevance has been covered only in a few studies. Focal active cryptitis (FAC) is a well-known manifestation of several etiologies; however, its prevalence and significance in colonic adenomas were not scrutinized. Likewise, whether the neutrophilic infiltrate of the lamina propria (LP) in colonic adenomas has a clinical or pathologic significance was not previously studied. We attempted to investigate the prevalence and importance of ABs in the cryptal epithelium and of neutrophils in the form of FAC and in the form of LP infiltrates in conventional colorectal adenomas. We conducted a retrospective review study over a 6-year period. We collected 223 conventional adenomas from 156 patients. We studied the interrelationship between these 3 histologic parameters and their potential association with other clinical and pathologic variables. Comparison controls included normal colonic mucosa, hyperplastic polyps, serrated adenomas, and flat adenomas. We found 91 (41%) adenomas to have crypt apoptosis, 40 (18%) to have FAC, and 69 (31%) to have neutrophilic infiltrate of the LP. We found ABs to be more frequent in high-grade adenomas. LP neutrophilic infiltrate was significantly associated with high-grade adenomas and in high-grade adenomas with invasive foci. In contrast, FAC was not associated with high-grade adenomas and was secondary to bowel preparations and drugs. Crypt apoptosis and LP neutrophils might have a potential prognostic value in predicting the biologic behavior of colonic adenomas. FAC in adenomas is a nonspecific finding of no prognostic significance and is related to external stimuli.