Publications by authors named "Talat Bessissow"

95 Publications

Comparative Efficacy of Biologic Therapies for Inducing Response and Remission in Fistulizing Crohn's Disease: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Inflamm Bowel Dis 2022 May 23. Epub 2022 May 23.

Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, Montreal, Quebec, Canada.

Background: The medical treatment of fistulizing Crohn's disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD.

Methods: We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI).

Results: In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55).

Conclusions: Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.
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http://dx.doi.org/10.1093/ibd/izac103DOI Listing
May 2022

Hereditary Nonpolyposis Colorectal Cancer in Association with Crohn's Disease and Lynch Syndrome: The Importance of a Strict Endoscopic Surveillance.

Case Rep Gastroenterol 2022 Jan-Apr;16(1):116-121. Epub 2022 Mar 17.

Division of Gastroenterology, McGill University Health Center, Montreal, Québec, Canada.

Crohn's disease (CD) and Lynch syndrome (LS) are two different entities, yet both are associated with increased risk of colorectal cancer (CRC). We present the case of a young female patient in long-standing remission of her ileocolonic luminal CD, and a family history of LS on a regular short interval (every 2 years) colonoscopy surveillance. Despite normal blood tests, fecal calprotectin, and ileocolonoscopy, her last colonoscopy showed an approximately 1.3-1.5 cm polyp in the cecum and mild UC-like colitis in the ascending colon. Histology confirmed the presence of a moderately differentiated adenocarcinoma (T2N0M0) with loss of PSM2 expression at immunohistochemistry, in line with a hereditary nonpolypoid CRC associated origin. Laparoscopic subtotal colectomy with ileorectal anastomosis was offered as the treatment of choice, which revealed a 2.4 cm exophytic ulcerated lesion and pathology confirmed invasive moderately differentiated adenocarcinoma (pT2N0M0). Patient will remain on close endoscopic surveillance for the rectum. Our case highlights the importance of a strict endoscopic surveillance in patients with long-standing CD colitis, especially in patients with additional risk factors. The aim of this article was to highlight the importance of a strict endoscopic surveillance in CD in association with LS regarding a higher risk of CRC, which mandates the adaptation of the endoscopic surveillance intervals as well as the surgical approach and postoperative management/surveillance.
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http://dx.doi.org/10.1159/000521919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035908PMC
March 2022

Is There a Best First Line Biological/Small Molecule in IBD: Are We Ready for Sequencing?

Biomedicines 2022 Mar 23;10(4). Epub 2022 Mar 23.

Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada.

Inflammatory bowel disease (IBD) is a chronic, life-long inflammatory condition of the gastrointestinal tract. Treatment strategy depends on the severity of the disease course. IBD physicians need to be aware of the life-long treatment options available. The goal is not only to achieve clinical remission but to halt or stabilize the chronic inflammation in the intestines to prevent further structural damage. Therefore, the use of early biologic therapy is recommended in moderate-to-severe IBD patients. However, in the last decade, use of therapeutic drug monitoring has increased considerably, opening an opportunity for sequencing. This review summarizes the available evidence on biologic and small molecules therapy in Crohn's disease (CD) and ulcerative colitis (UC) in different clinical scenarios, including perianal CD, the elderly, extra intestinal manifestations, and pregnancy.
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http://dx.doi.org/10.3390/biomedicines10040749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026422PMC
March 2022

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

Dig Dis Sci 2022 Mar 4. Epub 2022 Mar 4.

Division of Gastroenterology, Department of Medicine, McGill University Health Center, Montreal General Hospital 1650 Avenue Cedar C7-200, Montreal, QC, H3G 1A4, Canada.

Background: Treatment options for acute severe ulcerative colitis (ASUC) are limited. Tofacitinib, an approved treatment for moderate to severe ulcerative colitis, could be a potential rescue therapy for ASUC given its rapid onset of action.

Objective: To evaluate the effectiveness of tofacitinib in hospitalized patients with ASUC refractory to standard therapy in a real-world setting.

Methods: Retrospective observational study of hospitalized adult patients with ASUC treated with tofacitinib between January 2019 and September 2020 at five Canadian centers. We extracted patient demographics, clinical status, biomarkers (C-reactive protein and fecal calprotectin), endoscopic findings, and colectomy-free rate at admission, 30 days, 90 days, and 6 months after tofacitinib initiation.

Results: Eight patients with symptoms refractory to standard rescue therapy (corticosteroids ± infliximab if infliximab-naïve prior to admission) were treated with tofacitinib. During index hospitalization, clinical response was observed in 5/8 patients. The median time to discharge post-tofacitinib initiation was 5 days (IQR 5.0-6). At 30 and 90 days, all five responders were in clinical remission. At 6 months, only 3/5 responders remained in clinical remission. The colectomy-free rate was 37.5% during the follow-up period (two colectomies occurred within 30 days; one occurred within 90 days). No drug-related adverse reaction occurred.

Conclusion: In this small case-series, tofacitinib was an effective rescue therapy in patients with refractory ASUC. These findings need to be evaluated in a randomized controlled trial.
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http://dx.doi.org/10.1007/s10620-022-07439-2DOI Listing
March 2022

Increased Prevalence of Myocardial Infarction and Stable Stroke Proportions in Patients with Inflammatory Bowel Diseases in Quebec in 1996-2015.

J Clin Med 2022 Jan 28;11(3). Epub 2022 Jan 28.

Division of Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada.

Background: Chronic inflammatory diseases are linked to an increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is controversial. We therefore examined the risk of and risk factors for myocardial infarction (MI) and stroke in IBD patients.

Methods: We used the public health administrative database from the Province of Quebec, Canada, to identify IBD patients newly diagnosed between 1996 and 2015. The incidence and prevalence of MI and stroke in IBD patients were compared to those for the Canadian population.

Results: A cohort of 35,985 IBD patients was identified. The prevalence but not incidence rates of MI were higher in IBD patients (prevalence: 3.98%; incidence: 0.234) compared to the Canadian rates (prevalence: 2.0%; incidence: 0.220), while the prevalence and incidence rates of stroke were not significantly higher in the IBD patients (prevalence: 2.98%; incidence: 0.122, vs. Canadian rates: prevalence: 2.60%; incidence: 0.297). We identified age, female gender, hyperlipidemia, diabetes, and hypertension ( < 0.001 for each) as significant risk factors associated with MI and stroke in IBD. Exposure to biologics was associated with a higher incidence of MI (IRR: 1.51; 95% CI: 0.82-2.76; = 0.07) in the insured IBD population.

Conclusions: An increased prevalence but not incidence of MI and no increased risk of stroke were identified in this population-based IBD cohort.
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http://dx.doi.org/10.3390/jcm11030686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837182PMC
January 2022

Camu Camu effects on microbial translocation and systemic immune activation in ART-treated people living with HIV: protocol of the single-arm non-randomised Camu Camu prebiotic pilot study (CIHR/CTN PT032).

BMJ Open 2022 Jan 17;12(1):e053081. Epub 2022 Jan 17.

Research Institute of the McGill University Health Centre, McGill University Health Centre, Montreal, Quebec, Canada

Introduction: Despite the success of antiretroviral therapy (ART) in transforming HIV disease into a chronic infection, people living with HIV (PLWH) remain at risk for various non-AIDS inflammatory comorbidities. Risk of non-AIDS comorbidities is associated with gut dysbiosis, epithelial gut damage and subsequent microbial translocation, and increased activation of both circulating CD4+ and CD8+ T-cells. Therefore, in addition to ART, novel gut microbiota-modulating therapies could aid in reducing inflammation and immune activation, gut damage, and microbial translocation. Among various gut-modulation strategies under investigation, the Amazonian fruit Camu Camu (CC) presents itself as a prebiotic candidate based on its anti-inflammatory and antioxidant properties in animal models and tobacco smokers.

Method And Analysis: A total of 22 PLWH on ART for more than 2 years, with a viral load <50 copies/mL, a CD4 +count >200 and a CD4+/CD8 +ratio <1 (suggesting increased inflammation and risk for non-AIDS comorbidities), will be recruited in a single arm, non-randomised, interventional pilot trial. We will assess tolerance and effect of supplementation with CC in ART-treated PLWH on reducing gut damage, microbial translocation, inflammation and HIV latent reservoir by various assays.

Ethics And Dissemination: The Canadian Institutes of Health Research (CIHR)/Canadian HIV Trials Network (CTN) pilot trial protocol CTNPT032 was approved by the Natural and Non-prescription Health Products Directorate of Health Canada and the research ethics board of the McGill university Health Centre committee (number 2020-5903). Results will be made available as free access through publications in peer-reviewed journals and through the CIHR/CTN website.

Trial Registration Number: NCT04058392.
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http://dx.doi.org/10.1136/bmjopen-2021-053081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765027PMC
January 2022

Treatment Targets in Ulcerative Colitis: Is It Time for All In, including Histology?

J Clin Med 2021 Nov 26;10(23). Epub 2021 Nov 26.

Division of Gastroenterology, McGill University Health Center, Montreal, QC H3G 1A4, Canada.

The main therapeutic goal of ulcerative colitis (UC) is to induce and maintain remission to prevent long-term disease progression. Treat-to-target strategies, first introduced by the STRIDE consensus and updated in 2021, have shifted focus from symptomatic control toward more stringent objective endpoints. Today, patient monitoring should be based on a combination of biomarkers and clinical scores, while patient-reported outcomes could be used as short-term targets in monitoring disease activity and therapeutic response. In addition, endoscopic healing was the preferred long-term goal in UC. A Mayo endoscopic score (MES) ≤ 1 can be recommended as a minimum target. However, recent evidence suggests that more stringent endoscopic goals (MES of 0) are associated with superior outcomes. Recently, emerging data support that histological remission (HR) is a superior prognostic factor to endoscopic healing in predicting long-term remission. Despite not yet being recommended as a target, HR may become an important potential therapeutic goal in UC. However, it remains questionable if histological healing should be used as a routine assessment in addition to clinical, biomarker, and endoscopic targets in all patients. Therefore, in this review, our aim was to discuss the current evidence for the different treatment targets and their value in everyday clinical practice.
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http://dx.doi.org/10.3390/jcm10235551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658443PMC
November 2021

Clinical Outcomes of COVID-19 and Impact on Disease Course in Patients with Inflammatory Bowel Disease.

Can J Gastroenterol Hepatol 2021 30;2021:7591141. Epub 2021 Nov 30.

Division of Gastroenterology, McGill University Health Center, Montreal, Canada.

Background And Aims: The impact of COVID-19 has been of great concern in patients with inflammatory bowel disease (IBD) worldwide, including an increased risk of severe outcomes and/or possible flare of IBD. This study aims to evaluate prevalence, outcomes, the impact of COVID-19 in patients with IBD, and risk factors associated with severe COVID-19 or flare of IBD activity.

Methods: A consecutive cohort of IBD patients who were diagnosed with COVID-19 infection and followed up at the McGill University Health Care Centre was obtained between March 1, 2020, and April 30, 2021. Demographics, comorbidities, IBD (type, treatments, pre- and post-COVID-19 clinical activity, biomarkers, and endoscopic activity), and COVID-19-related outcomes (pneumonia, hospitalization, death, and flare of IBD disease) were analyzed.

Results: A cohort of 3,516 IBD patients was included. 82 patients (2.3%) were diagnosed with COVID-19 infection (median age: 39.0 (IQR 27.8-48.0), 77% with Crohn's disease, 50% were female). The prevalence of COVID-19 infection in IBD patients was significantly lower compared to the general population in Canada and Quebec (3.5% versus 4.3%, < 0.001). Severe COVID-19 occurred in 6 patients (7.3%); 2 patients (2.4%) died. A flare of IBD post-COVID-19 infection was reported in 8 patients (9.8%) within 3 months. Biologic therapy was held during active COVID-19 infection in 37% of patients. Age ≥55 years (odds ratio (OR): 11.1, 95% CI: 1.8-68.0), systemic corticosteroid use (OR: 4.6, 95% CI: 0.7-30.1), active IBD (OR: 3.8, 95% CI: 0.7-20.8), and comorbidity (OR: 4.9, 95% CI: 0.8-28.6) were factors associated with severe COVID-19. After initial infection, 61% of IBD patients received COVID-19 vaccinations.

Conclusion: The prevalence of COVID-19 infection among patients with IBD was lower than that in the general population in Canada. Severe COVID-19, mortality, and flare of IBD were relatively rare, while a large proportion of patients received COVID-19 vaccination. Older age, comorbidities, active IBD disease, and systemic corticosteroid, but not immunosuppressive or biological therapy, were associated with severe COVID-19 infection.
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http://dx.doi.org/10.1155/2021/7591141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632463PMC
December 2021

Tofacitinib-Associated Iatrogenic Kaposi Sarcoma in a Patient With Ulcerative Colitis.

ACG Case Rep J 2021 Nov 23;8(11):e00678. Epub 2021 Nov 23.

Division of Gastroenterology, McGill University Health Center, Montreal, Canada.

Tofacitinib is an oral Janus kinase inhibitor. Although it contributes to the induction and maintenance of clinical remission of patients with moderate-to-severe ulcerative colitis, various malignancies have been reported after the use of this small molecule. We report a rare case of biopsy-proven Kaposi sarcoma in a patient with complex biological-resistant ulcerative colitis after 2 years of treatment with tofacitinib. Kaposi sarcoma lesions spontaneously regressed after tofacitinib was discontinued. Given the concern of potential risk of malignancy associated with this agent, we believe that specialists should be aware of this rare but serious possible adverse event.
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http://dx.doi.org/10.14309/crj.0000000000000678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613348PMC
November 2021

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

J Clin Gastroenterol 2022 03;56(3):e166-e170

Division of Gastroenterology and Hepatology, McGill University Health Centre.

Background: Fucosyltransferase 2 (FUT2) participates in intestinal antigen secretion and bacterial adherence. FUT2 homozygous nonsense mutations (FUT2M) and subsequent nonsecretor status is associated with Crohn's disease (CD). The common null allele is rs601338. We assessed the relationship between FUT2M and disease course.

Methods: In consecutive adult CD outpatients, clinical, biochemical, and genetic data were collected at baseline visits. Patients were longitudinally followed over 5 years. The primary outcome analyzed the relationship between FUT2M and rates of CD patients in persistent steroid-free clinical remission requiring neither surgery, biologics, nor immunomodulators.

Results: Sixty-two CD patients were recruited. FUT2M homozygotes (rs601338 or any mutation in linkage disequilibrium) were detected in 27% of CD (17/62). Patients with rs601338 mutations had higher rates of the primary outcome (homozygous: 46.6%, heterozygous: 28.0%, wild-type: 5.3%, P=0.02). Similar findings existed for CD patients with homozygous mutations in any single-nucleotide polymorphism for FUT2 (homozygous: 41.2%, heterozygous: 25.9%, wild-type: 5.6%, P=0.04). On multivariable analysis, rs601338 mutation was associated with the primary outcome (odds ratio=3.4, 95% confidence interval: 1.3-8.7, P=0.01), while other parameters were not. Mutation of rs601338 was associated with lower rates of penetrating disease (homozygous: 13.3%, heterozygous: 28.0%, wild-type: 52.6%, P=0.05) and particularly in high-risk patients (homozygous: 0%, heterozygous: 37.5%, wild-type: 83.3%, P=0.01).

Conclusions: FUT2 mutation status is associated with a favorable clinical course in CD. Further confirmatory studies are needed.
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http://dx.doi.org/10.1097/MCG.0000000000001626DOI Listing
March 2022

Therapeutic drug monitoring in inflammatory bowel disease: The dawn of reactive monitoring.

World J Gastroenterol 2021 Oct;27(37):6231-6247

Division of Gastroenterology, McGill University, Montreal H3G 1A4, Quebec, Canada.

Inflammatory bowel disease (IBD) is a chronic condition that significantly affects the quality of life of its patients. Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution, there remains a proportion of patients that do not respond or lose response to treatment. Therapeutic drug monitoring (TDM) involves measuring levels of serum drug concentrations and anti-drug antibodies. TDM of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory diseases. This was then introduced in IBD to rationalize primary non-response or secondary loss of response, given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment failure. The aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations, in everyday practice. A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management, through an electronic search using PubMed and ScienceDirect. TDM has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in treatment. Despite a trend towards an association between clinical outcomes and drug concentrations, proactive TDM based strategies have not been shown to achieve clear benefit in long-term outcomes. In the clinical setting, TDM has proven to be useful in managing IBD patients, and its use in the reactive setting, as an additional tool to help manage patients with treatment failure, is being promoted as newer guidelines and consensus groups implement TDM as part of the management plan.
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http://dx.doi.org/10.3748/wjg.v27.i37.6231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515794PMC
October 2021

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

J Can Assoc Gastroenterol 2021 Aug 29;4(4):e72-e91. Epub 2021 Jul 29.

Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.

Background And Aims: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines.

Methods: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients.

Results: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years.

Conclusions: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.
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http://dx.doi.org/10.1093/jcag/gwab016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407486PMC
August 2021

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 1: Live Vaccines.

J Can Assoc Gastroenterol 2021 Aug 29;4(4):e59-e71. Epub 2021 Jul 29.

Department of Medicine and Community Health and Epidemiology, Dalhousie University, Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada.

Background & Aims: Patients with inflammatory bowel disease (IBD) may be at increased risk of some vaccine-preventable diseases. The effectiveness and safety of vaccinations may be altered by immunosuppressive therapies or IBD itself. These recommendations, developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in patients with inflammatory bowel disease. This publication focused on live vaccines.

Methods: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative process and voted on by a multidisciplinary panel. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients.

Results: Three good practice statements included reviewing a patient's vaccination status at diagnosis and at regular intervals, giving appropriate vaccinations as soon as possible, and not delaying urgently needed immunosuppressive therapy to provide vaccinations. There are 4 recommendations on the use of live vaccines. Measles, mumps, rubella vaccine is recommended for both adult and pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). Varicella vaccine is recommended for pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). For adults, recommendations are conditionally in favor of varicella vaccine for those not on immunosuppressive therapy, and against for those on therapy. No recommendation was made regarding the use of live vaccines in infants born to mothers using biologics because the desirable and undesirable effects were closely balanced and the evidence was insufficient.

Conclusions: Maintaining appropriate vaccination status in patients with IBD is critical to optimize patient outcomes. In general, live vaccines are recommended in patients not on immunosuppressive therapy, but not for those using immunosuppressive medications. Additional studies are needed to evaluate the safety and efficacy of live vaccines in patients on immunosuppressive therapy.
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http://dx.doi.org/10.1093/jcag/gwab015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407487PMC
August 2021

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

Gastroenterology 2021 08;161(2):681-700

Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada, CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario and CHEO Research Institute, Ottawa, Ontario, Canada, ICES Ottawa, Ottawa, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada, SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology Hepatology and Nutrition, The Hospital for Sick Children, Child Health Evaluative Sciences, SickKids Research Institute, ICES, Toronto, Ontario, Canada. Electronic address:

Background And Aims: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines.

Methods: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients.

Results: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years.

Conclusions: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.
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http://dx.doi.org/10.1053/j.gastro.2021.04.034DOI Listing
August 2021

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

Dig Dis Sci 2022 Jul 20;67(7):3089-3095. Epub 2021 Jul 20.

1st Department of Medicine, Semmelweis University, Koranyi S u 2/a, Budapest, 1083, Hungary.

Background: Optimal management of patients with ulcerative colitis (UC) requires the accurate, objective assessment of disease activity.

Aims: We aimed to determine how strong patient-reported outcomes, clinical scores and symptoms correlate with endoscopy and biomarkers for assessment of disease activity in patients with UC.

Methods: Consecutive patients with UC followed at the McGill University IBD Center and referred for endoscopy (surveillance or flare) were included prospectively between September 2018 and August 2020. Patient-reported outcome (PRO2), partial Mayo, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES) and Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C-reactive protein (CRP) and fecal calprotectin (FCAL) were collected.

Results: A total of 171 patients with UC [age: 49(IQR:38-61) years, female: 46.2%, 57.3% extensive disease, 42.7% on biologicals] were included prospectively. Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS0 and SF ≤ 1), partial Mayo (≤ 2) and SCCAI (≤ 2.5) remission were similarly associated with mucosal healing defined by MES (0 or ≤ 1), Baron (0 or ≤ 1) or UCEIS (≤ 3) scores in ROC analysis (AUC:0.93-0.72). There was a moderate-to-strong agreement between MES Baron and UCEIS (K = 0.91-0.41). A UCEIS of ≤ 3 was identified as the best cutoff to clinical or endoscopic remission. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K ~ 0.2), while agreement between FCAL and RBS-PRO2 or MES/Baron/UCEIS was moderate to strong (K = 0.44-0.70).

Conclusions: Agreement between RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing was moderate to strong, while no clinically meaningful difference was found in accuracy across the scores and definitions. FCAL, but not CRP, was associated to clinical and endoscopic remission.
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http://dx.doi.org/10.1007/s10620-021-07178-wDOI Listing
July 2022

Subcutaneously Administered Anti-TNFs for the Treatment of Ulcerative Colitis: A Retrospective, Propensity Score-Matched, US Health Claims Analysis.

Adv Ther 2021 07 22;38(7):4115-4129. Epub 2021 Jun 22.

Janssen Inc., 19 Green Belt Dr, Toronto, ON, M3C 1L9, Canada.

Introduction: Adalimumab and golimumab are subcutaneously administered anti-tumor necrosis factor α (TNFα) biologics used in the treatment of ulcerative colitis (UC). To date, no studies have directly compared treatment patterns and healthcare resource utilization (HRU) among patients with UC receiving these therapies in a real-world setting. The objective of this study was to compare these outcomes among patients with UC treated with either adalimumab or golimumab using a US claims database.

Methods: Patients with UC treated with golimumab or adalimumab were identified using the US Optum Clinformatics Data Mart database. Outcomes of interest included treatment patterns (discontinuations, dose optimizations, persistence, and concomitant medication use) and HRU (outpatient office visits, emergency room [ER] visits, and inpatient stays). Propensity score matching (PSM) was used to account for differences in confounding variables between groups.

Results: Overall, 990 patients were identified (golimumab: n = 277; adalimumab: n = 713). After PSM, 246 patients were included in each group. There were no significant differences between the adalimumab and golimumab groups over the full follow-up period in terms of treatment discontinuations (53.7% vs. 51.2%; P = 0.5881), dose optimizations (35.4% vs. 39.4%; P = 0.3515), or persistence (338.2 vs. 361.2 days; P = 0.4194). During the year after initiating therapy, there were no significant differences in concomitant immunosuppressant (21.9% vs. 21.7%; P = 0.9686) or corticosteroid use (74.7% vs. 78.8%; P = 0.3573) or in HRU outcomes including outpatient office visits (93.3% vs. 94.0%; P = 0.7660), ER visits (15.2% vs. 10.9%; P = 0.2238), and inpatient stays (15.2% vs. 13.6%; P = 0.6680).

Conclusions: In this nationwide PSM cohort study of patients with UC receiving golimumab or adalimumab, no significant differences were observed between groups for treatment patterns or HRU outcomes. High rates of concomitant corticosteroid use, treatment discontinuations, and HRU while on therapy highlight key unmet needs in the treatment of UC.
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http://dx.doi.org/10.1007/s12325-021-01818-3DOI Listing
July 2021

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

Dig Dis Sci 2022 Jun 21;67(6):1956-1974. Epub 2021 May 21.

Division of Gastroenterology, Department of Medicine, McGill University, Montreal, Canada.

Background: In this systematic review, our objective was to assess inflammatory bowel disease (IBD) patient preferences and perspectives relating to their disease diagnosis, treatment, knowledge needs and telemedicine.

Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases and conference proceedings were searched between January 1, 1980, and May 1, 2020. The methodological quality of the included studies was assessed using the Standards for reporting qualitative research checklist.

Results: Our search identified 240 citations and 52 studies met the inclusion criteria. The major expectations of the patients are symptomatic and pain control, quality of life and normal endoscopy. Patients' main concerns are access to information and healthcare, and shared decision making. At the time of diagnosis, patients expressed a greater need for knowledge about their IBD, preferentially by their treating gastroenterologist. The main treatment expectations in active disease are efficacy, safety and convenience. Patients are willing to accept relatively high risks of complications from medical therapy to avoid a permanent ostomy and to achieve durable remission. Patients are more interested in disease monitoring, research and development during the time of remission. Telemedicine and self-management with supervised e-health tools are feasible and acceptable amongst patients with IBD.

Conclusion: This systematic review demonstrates that patients with IBD expect more information about their disease process, shared decision making and symptom control. Further research is needed to help align patient and physician expectations in order to improve the quality of care provided to patients with IBD.
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http://dx.doi.org/10.1007/s10620-021-07025-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139371PMC
June 2022

Anti-TNF Therapy and the Risk of Herpes Zoster Among Patients With Inflammatory Bowel Disease.

Inflamm Bowel Dis 2022 02;28(2):176-182

Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada.

Background: The specific contribution of anti-TNF therapy to the onset of herpes zoster (HZ) in patients with inflammatory bowel disease (IBD) remains uncertain. Thus, the purpose of this nested case-control study was to explore whether the use of anti-TNF therapy is associated with an increased risk of HZ.

Methods: Using the Regie de l'Assurance Maladie du Québec, we identified incident cases of IBD between 1998 and 2015. We matched IBD cases of HZ with up to 10 IBD HZ-free controls on year of cohort entry and follow-up. Current use was defined as a prescription for anti-TNF therapy 60 days before the index date, with nonuse as the comparator. We conducted conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for potential confounders.

Results: The cohort consisted of 15,454 incident IBD patients. Over an average follow-up of 5.0 years, 824 patients were diagnosed with HZ (incidence of 9.3 per 1000 person-years). Relative to nonuse, current use of anti-TNF therapy was associated with an overall increased risk of HZ (OR, 1.5; 95% CI, 1.1-2.1). The risk was increased among those older than 50 years (OR, 2.1; 95% CI, 1.2-3.6) and those additionally using steroids and immunosuppressants (OR, 4.1; 95% CI, 2.3-7.2).

Conclusions: Use of anti-TNF therapy was associated with an increased risk of HZ among patients with IBD, particularly among those older than 50 years and those on combination therapy. Prevention strategies for HZ ought to be considered for younger IBD patients commencing treatment.
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http://dx.doi.org/10.1093/ibd/izab092DOI Listing
February 2022

Fecal Diversion for Perianal Crohn Disease in the Era of Biologic Therapies: A Multicenter Study.

Inflamm Bowel Dis 2022 02;28(2):226-233

Department of Medicine, University of British Columbia, Vancouver, Canada.

Background: The natural history of perianal Crohn disease (PCD) after fecal diversion in the era of biologics is poorly understood. We assessed clinical and surgical outcomes after fecal diversion for medically refractory PCD and determined the impact of biologics.

Methods: We performed a retrospective, multicenter study from 1999 to 2020. Patients who underwent fecal diversion for refractory PCD were stratified by diversion type (ostomy with or without proctectomy). Times to clinical and surgical outcomes were estimated using Kaplan-Meier methods, and the association with biologics was assessed using multivariable Cox proportional hazards models.

Results: Eighty-two patients, from 3 academic institutions, underwent a total of 97 fecal diversions: 68 diversions without proctectomy and 29 diversions with proctectomy. Perianal healing occurred more commonly after diversion with proctectomy than after diversion without proctectomy (83% vs 53%; P = 0.021). Among the patients who had 68 diversions without proctectomy, with a median follow-up of 4.9 years post-diversion (interquartile range, 1.66-10.19), 37% had sustained healing, 31% underwent surgery to restore bowel continuity, and 22% underwent proctectomy. Ostomy-free survival occurred in 21% of patients. Biologics were independently associated with avoidance of proctectomy (hazard ratio, 0.32; 95% confidence interval, 0.11-0.98) and surgery to restore bowel continuity (hazard ratio, 3.10; 95% confidence interval, 1.02-9.37), but not fistula healing.

Conclusions: In this multicenter study, biologics were associated with bowel restoration and avoidance of proctectomy after fecal diversion without proctectomy for PCD; however, a minority of patients achieved sustained fistula healing after initial fecal diversion or after bowel restoration. These results highlight the refractory nature of PCD.
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http://dx.doi.org/10.1093/ibd/izab086DOI Listing
February 2022

Novel Negative Pressure Protective Box in Upper Digestive Endoscopy: A Prospective Case Series.

Am J Gastroenterol 2021 06;116(6):1339-1341

Division of Gastroenterology and Hepatology, McGill University Health Center, McGill University, Montreal, Quebec, Canada.

In the context of the Severe Acute Respiratory Syndrome Coronavirus 2 pandemic, we have developed a novel negative pressure aerosol protector for upper endoscopy (TRACEY). TRACEY is the first endoscopic enclosure to have passed stringent testing for aerosol protection. The following describes its clinical use in a single-center prospective case series. Overall, 15 patients were included. All endoscopic procedures were successful without premature removal of TRACEY. In addition, its use did not lead to significant patient discomfort, technical hinderance, or adverse events. TRACEY seems to offer a safe and easy to use aerosol protection for upper endoscopy and a potential Severe Acute Respiratory Syndrome Coronavirus 2 mitigation strategy in endoscopy.
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http://dx.doi.org/10.14309/ajg.0000000000001221DOI Listing
June 2021

Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis.

J Virus Erad 2021 Mar 15;7(1):100033. Epub 2021 Feb 15.

Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montréal, QC, Canada.

The greatest obstacle to an HIV cure is the persistence of latently infected cellular reservoirs in people living with HIV (PLWH) taking antiretroviral therapy (ART). However, no consensus exists on the direct link between local tissue inflammation and the HIV burden. Herein, we have compared the levels of local inflammation, epithelial integrity and HIV DNA between inflamed and non-inflamed colon tissue in a PLWH who underwent a colectomy due to ulcerative colitis. We have observed a 27-fold higher frequency of cells harboring HIV DNA in inflamed compared to non-inflamed colon tissue. Analysis of the expression of occludin-1 and claudin-3 confirmed our macroscopic characterization of inflamed and non-inflamed colon. Our results confirm that increased gut permeability and inflammation are associated with a higher frequency of infected cells and suggest that restoring gut barrier integrity may be used as a strategy to reduce inflammation and HIV persistence in the gut.
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http://dx.doi.org/10.1016/j.jve.2021.100033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906891PMC
March 2021

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 1: Live Vaccines.

Gastroenterology 2021 08 19;161(2):669-680.e0. Epub 2021 Feb 19.

Department of Medicine and Community Health and Epidemiology, Dalhousie University, Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada.

Background & Aims: Patients with inflammatory bowel disease (IBD) may be at increased risk of some vaccine-preventable diseases. The effectiveness and safety of vaccinations may be altered by immunosuppressive therapies or IBD itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on live vaccines.

Methods: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative process and voted on by a multidisciplinary panel. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients.

Results: Three good practice statements included reviewing a patient's vaccination status at diagnosis and at regular intervals, giving appropriate vaccinations as soon as possible, and not delaying urgently needed immunosuppressive therapy to provide vaccinations. There are 4 recommendations on the use of live vaccines. Measles, mumps, rubella vaccine is recommended for both adult and pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). Varicella vaccine is recommended for pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). For adults, recommendations are conditionally in favor of varicella vaccine for those not on immunosuppressive therapy, and against for those on therapy. No recommendation was made regarding the use of live vaccines in infants born to mothers using biologics because the desirable and undesirable effects were closely balanced and the evidence was insufficient.

Conclusions: Maintaining appropriate vaccination status in patients with IBD is critical to optimize patient outcomes. In general, live vaccines are recommended in patients not on immunosuppressive therapy, but not for those using immunosuppressive medications. Additional studies are needed to evaluate the safety and efficacy of live vaccines in patients on immunosuppressive therapy.
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http://dx.doi.org/10.1053/j.gastro.2020.12.079DOI Listing
August 2021

Use of various immunotherapies for refractory ulcerative colitis in a person living with HIV: a case report.

Oxf Med Case Reports 2021 Jan 23;2021(1):omaa131. Epub 2021 Jan 23.

Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada.

Cancer therapies include several immune checkpoint or anticytokine therapies whereas ulcerative colitis treatments consist of anticytokine therapies. The development of tolerance and immunogical effects of these agents in people living with HIV are not well assessed as these persons are often excluded from clinical trials. Herein, we report a case of a Caucasian woman who received multiple sequential immunotherapies for severe ulcerative colitis. Due to steroid-refractory disease, receipt of maximal doses of mesalamine and initial repeated decline of surgical intervention, she went on to receive biologic immune inhibitors like tumor necrosis fator-α blockers infliximab and adalimumab, the αβintegrin blocker vedolizumab, anti-interleukin 12/23 blocker ustekinumab and Janus Kinase inihibitor tofacitinib without achieving remission. Only minor infectious complications were encountered and no significant changes in CD4 count nor CD4/CD8 ratio occurred. This case provides support for the safety and tolerability of the above immunotherapies in people living with HIV with suppressed viral load on antiretroviral therapy.
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http://dx.doi.org/10.1093/omcr/omaa131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846135PMC
January 2021

The Burden of Anemia Remains Significant over Time in Patients with Inflammatory Bowel Diseases at a Tertiary Referral Center.

J Gastrointestin Liver Dis 2020 Dec 12;29(4):555-559. Epub 2020 Dec 12.

McGill University, Division of Gastroenterology Department of Medicine, Montreal, Canada; Semmelweis University, 1st Department of Medicine, Budapest, Hungary.

Background And Aims: Anemia is a common complication of inflammatory bowel diseases (IBD), as well as a predictor of poor outcomes. The aim of this study was to determine the prevalence of anemia over time and the management of moderate to severe anemia at a tertiary referral IBD center.

Methods: We retrospectively reviewed the occurrence of anemia at the time of referral or diagnosis and during follow-up at the McGill University Health Centre IBD center. Consecutive patients presenting with an outpatient visit between July and December 2016 and between December 2018 and March 2019 were included. Disease characteristics, biochemistry and medical management, including the need for intravenous iron therapy were recorded.

Results: 1,356 Crohn's disease (CD) and 1,293 ulcerative colitis (UC) patients [disease duration: 12 (IQR: 6-22) and 10 (IQR: 5-19) years respectively] were included. The prevalence of moderate to severe anemia at referral/diagnosis (15.4% and 8.5%) and during follow-up (11.1% and 8.1%) were higher in CD than in UC patients. In CD, previous resective surgery, perianal disease and elevated C-reactive protein (CRP) at assessment, while in UC steroid therapy, an elevated CRP and fecal calprotectin at assessment were associated with anemia in a multivariate analysis. Anemia improved by >2g/dL in 56.5% after 4-6 weeks (intravenous iron dose >1000 mg in 87% of patients).

Conclusion: Anemia occurred frequently in this IBD cohort, at referral to the center and during follow-up, and contributes to the burden of IBD in referral populations. Most patients were assessed for anemia regularly and with accurate anemia workup; however, the targeted management of moderate to severe anemia was suboptimal.
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http://dx.doi.org/10.15403/jgld-2705DOI Listing
December 2020

Adenocarcinoma Within Carpet-Like Pseudopolyposis.

ACG Case Rep J 2020 Jun 23;7(6):e00415. Epub 2020 Jun 23.

Division of Gastroenterology, McGill University, Montreal, Quebec, Canada.

Pseudopolyps are benign lesions without malignant potential and typically do not require biopsy or excision. We describe a 68-year-old man with ulcerative colitis found to have multiple large bridging pseudopolyps. Repeated colonoscopies and extensive biopsies revealed a large ulcerated lesion previously hidden within the pseudopolyps. The pathology of the lesion was consistent with a low-grade adenocarcinoma with invasion into the muscularis propria. This demonstrates that large pseudopolyps, although benign, can obscure other lesions with malignant potential. Therefore, in addition to careful inspection, healthcare providers must perform periodic surveillance colonoscopies and offer surgical resection to patients with giant pseudopolyposis.
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http://dx.doi.org/10.14309/crj.0000000000000415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535685PMC
June 2020

Do You See What I See? An Assessment of Endoscopic Lesions Recognition and Description by Gastroenterology Trainees and Staff Physicians.

J Can Assoc Gastroenterol 2020 Oct 19;3(5):216-221. Epub 2019 Jun 19.

Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada.

Background: Gastroenterologists should accurately describe endoscopic findings and integrate them into management plans. We aimed to determine if trainees and staff are describing inflammatory bowel disease (IBD) lesions in a similar manner.

Methods: Using 20 ileocolonoscopy images, participants described IBD inflammatory burden based on physician severity rating, and Mayo endoscopic score (MES) (ulcerative colitis [UC]) or simple endoscopic score (SES-CD) (Crohn's disease [CD]). Images were selected based on agreement by three IBD experts. Findings of varying severity were presented; 10 images included a question about management. We examined inter-observer agreement among trainees and staff, compared trainees to staff, and determined accuracy of response comparing both groups to IBD experts.

Results: One hundred and twenty-nine staff and 47 trainees participated from across Canada. There was moderate inter-rater agreement using physician severity rating (κ = 0.53 UC and 0.52 CD for staff, κ = 0.51 UC and 0.43 CD for trainees). There was moderate inter-rater agreement for MES for staff and trainees (κ = 0.49 and 0.48, respectively), but fair agreement for SES-CD (κ = 0.37 and 0.32, respectively). For accuracy of response, the mean score was 68.7% for staff and 63.7% for trainees ( = 0.028). Both groups identified healed bowel or severe disease better than mild/moderate ( < 0.05). There was high accuracy for management, but staff scored higher than trainees for UC ( < 0.01).

Conclusion: Inter-rater agreement on description of IBD lesions was moderate at best. Staff and trainees more accurately describe healed and severe disease, and better describe lesions in UC than CD.
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http://dx.doi.org/10.1093/jcag/gwz022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465549PMC
October 2020

No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015.

Inflamm Bowel Dis 2021 04;27(5):655-661

Division of Gastroenterology, McGill University Health Centre, Montreal, Québec, Canada.

Background: Crohn disease (CD) and ulcerative colitis (UC) have high health care expenditures because of medications, hospitalizations, and surgeries. We evaluated disease outcomes and treatment algorithms of patients with inflammatory bowel disease (IBD) in Québec, comparing periods before and after 2010.

Methods: The province of Québec's public health administrative database was used to identify newly diagnosed patients with IBD between 1996 and 2015. The primary and secondary outcomes included time to and probability of first and second IBD-related hospitalizations, first and second major surgery, and medication exposures. Medication prescriptions were collected from the public prescription database.

Results: We identified 34,644 newly diagnosed patients with IBD (CD = 59.5%). The probability of the first major surgery increased after 2010 in patients with CD (5 years postdiagnosis before and after 2010: 8% [SD = 0.2%] vs 15% [SD = 0.6%]; P < 0.0001) and patients with UC (6% [SD = 0.2%] vs 10% [SD = 0.6%] ;P < 0.0001). The probability of the second major surgery was unchanged in patients with CD. Hospitalization rates remained unchanged. Patients on anti-tumor necrosis factor (anti-TNF) medications had the lowest probability of hospitalizations (overall 5-year probability in patients with IBD stratified by maximal therapeutic step: 5-aminosalicylic acids 37% [SD = 0.6%]; anti-TNFs 31% [SD = 1.8%]; P < 0.0001). Anti-TNFs were more commonly prescribed for patients with CD after 2010 (4% [SD = 0.2%] vs 16% [SD = 0.6%]; P < 0.0001) in the public health insurance plan, especially younger patients. Corticosteroid exposure was unchanged before and after 2010. Immunosuppressant use was low but increased after 2010. The use of 5-ASAs was stable in patients with UC but decreased in patients with CD.

Conclusions: The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs.
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http://dx.doi.org/10.1093/ibd/izaa166DOI Listing
April 2021

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

Dig Dis Sci 2021 05 26;66(5):1650-1657. Epub 2020 Jun 26.

Division of Gastroenterology, Montreal General Hospital, McGill University Health Center, 1650 Cedar Avenue, C7-200, Montreal, QC, H3G 1A4, Canada.

Background: Immunomodulator monotherapy is an important component in the treatment of inflammatory bowel disease (IBD). However, there is conflicting literature about thiopurines maintaining long-term remission in patients with active IBD.

Aim: To determine the durable clinical remission rate in adults with Crohn's disease (CD) or ulcerative colitis (UC) on thiopurine monotherapy over 5 years.

Methods: We performed a retrospective analysis of adult patients identified at McGill University Health Centre from 2009 to 2012. We included IBD patients who initiated thiopurine monotherapy and were in remission for at least 3 months (Harvey-Bradshaw Index (HBI) < 5 points for CD and partial Mayo Score (pMS) < 2 points in UC). The primary endpoint was sustained clinical remission on thiopurines during a 5-year follow-up. This included patients who had not relapsed or discontinued the drug due to side effects. The secondary endpoint was clinical relapse over the follow-up period, which was defined as HBI > 5 in CD and pMS > 2 in UC.

Results: There were 148 patients included in the study (100 CD; 48 UC). At 5 years, 23% (34/148) patients remained in clinical remission on thiopurine monotherapy (25 CD and 9 UC patients). Thirty-three percent (33/100) of CD and 46% (22/48) of UC patients relapsed while on thiopurines. There was no difference in relapse rates between CD and UC patients. Eighty-four percent (42/50) of patients with CD with side effects and all UC (17/17) patients who experienced side effects discontinued the drug.

Conclusion: This analysis demonstrates that there is poor sustainability of clinical remission in IBD patients on thiopurine monotherapy given that a high proportion of patients discontinue thiopurines due to either relapse or side effects.
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http://dx.doi.org/10.1007/s10620-020-06427-8DOI Listing
May 2021

Esophageal Squamous Cell Carcinoma With Colonic Metastases.

ACG Case Rep J 2020 Feb 24;7(2):e00335. Epub 2020 Feb 24.

Division of Gastroenterology, McGill University, Montreal, Quebec, Canada.

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the most lethal malignancies worldwide. The disease's tendency to quickly metastasize precludes many patients from receiving curative therapy. The most common sites of distal metastases include the liver, lungs, bones, and brain. We report a case of ESCC metastasizing to the rectosigmoid region years after treatment with neoadjuvant chemoradiation and esophagectomy. To our knowledge, only a handful of cases of ESCC with colonic metastases have been previously documented.
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http://dx.doi.org/10.14309/crj.0000000000000335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145180PMC
February 2020

Concordance between tuberculin skin test and interferon-gamma release assay for latent tuberculosis screening in inflammatory bowel disease.

Intest Res 2020 Jul 20;18(3):306-314. Epub 2020 Mar 20.

Department of Gastroenterology, McGill University, Montreal, QC, Canada.

Background/aims: Latent tuberculosis screening is mandatory prior to initiating anti-tumor necrosis factor (anti-TNF) medications. Guidelines recommend interferon-gamma release assays (IGRA) as first line screening method for the general population. Studies provided conflicting evidence on IGRA and tuberculin skin test (TST) performance in inflammatory bowel disease (IBD) patients. We assessed test concordance and the effects of immunosuppression on their performance in IBD patients.

Methods: We searched MEDLINE, Embase and Cochrane databases (2011-2018) for studies testing TST and IGRA in IBD. Primary outcome was TST and IGRA concordance. Secondary outcomes were effects of immunosuppressive therapy on performance. Immunosuppression defined as either steroids, thiopurine, methotrexate or cyclosporine use. We used the pooled random effects model to adjust for heterogeneity analyzed using (I2-Q statistics). We compared the fixed model to exclude smaller study effects.

Results: Sixteen studies (2,488 patients) were included. Pooled TST and IGRA concordance was 85% (95% confidence interval [CI], 81%-88%; P=0.01). Effects of immunosuppression were reported in 8 studies (814 patients). The odds ratio of testing positive by IGRA decreased to 0.57 if immunosuppressed (95% CI, 0.31-1.03; P=0.06). The odds ratio of testing positive by TST if immunosuppressed was 1.14 (95% CI, 0.61-2.12; P=0.69). The fixed model yielded similar results, however the negative effect of immunosuppression on IGRA reached statistical significance (P=0.01).

Conclusions: While concordance was 85% between TST and IGRA, the performance of IGRA seems to be negatively affected by immunosuppression. Given the importance of detecting latent tuberculosis prior to anti-TNF initiation, further randomized controlled trials comparing the performance of TST and IGRA in IBD patients are needed.
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http://dx.doi.org/10.5217/ir.2019.00116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385575PMC
July 2020
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