Inflammatory bowel disease burden in the Middle East and North Africa Region: a comprehensive analysis of incidence, prevalence, and mortality from 1990-2019.

Background: The epidemiology of inflammatory bowel disease (IBD) has changed rapidly in recent years. Objective data concerning the IBD burden in the Middle East and North Africa (MENA) region is limited. We aimed to provide a systematic report on the IBD burden in the MENA region. Additionally, we aimed to study the age- and sex-specific trends in IBD incidence, prevalence and mortality rates from 1990-2019. Methods: Using the Global Burden of Disease (GBD) 2019 Study Database, we investigated the changes in incidence, prevalence and mortality rate, and disability-adjusted life-years (DALYs), at a regional and country level between 1990 and 2019. Results: In 2019, there were 282,534 cases (95% confidence interval [CI] 239,506-334,478) of IBD in the MENA region (50.5% male). There was an overall increase in the incidence and prevalence rates of IBD in the MENA region from 1990 to 2019, while a simultaneous decrease in overall mortality rates was identified. Incidence rates were highest in Jordan, at 6.9 (95%CI 5.8-8.1) per 100,000, and lowest in Morocco, at 1.6 (95%CI 1.4-2) per 100,000. From 1990-2019, the incidence was found increased in males at a higher rate than in females. The age-standardized mortality rate decreased for both sexes by 24% from 1990-2019. Conclusion: The trends and geographic variations in IBD within the MENA region provide policymakers with vital information for making informed decisions in policy, research, and investment, thereby enabling the development of more effective strategies and better allocation of resources.

Saudi consensus guidance for the diagnosis and management of inflammatory bowel disease in children and adolescents.

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

Inflammatory bowel disease training assessment of gastroenterology fellows in Saudi Arabia.

BACKGROUND: Recent advancement and complexity in the management of inflammatory bowel disease (IBD) has made it challenging for gastroenterology (GI) fellows to obtain competency and confidence in managing the complex IBD patient. We aimed to evaluate the confidence and training in IBD among GI fellows in Saudi Arabia. METHODS: We conducted an electronic, voluntary, and anonymous multicenter survey study of GI fellows in Saudi Arabia, from 1/5/2023 to 1/9/2023. The survey evaluated the fellows' confidence level in IBD management, methods of training received, and the amount of additional training desired in 20 core IBD domains. GI fellows' preferred learning method was also evaluated. RESULTS: A total of 65 GI fellows responded to the survey. In the entire cohort, >50% of fellows reported low confidence in 7 out of 20 IBD management domains, which included 71% in managing j-pouch disorders, 67% in managing the elderly/frail patient with IBD, 60% in managing extraintestinal manifestations, 57% in recommending preventative health services, and 54% in counseling patients on small molecules. Receiving >4 IBD didactic sessions per year was significantly associated with high confidence in managing j-pouch disorders (44.4% vs 13.3%, P = 0.05) and managing the elderly/frail patient with IBD (86.7% vs 50.0%, P = 0.03). Doing an external rotation to expand IBD knowledge was associated with high confidence in managing the elderly/frail patient with IBD (100% vs 26.7%, P = 0.01). CONCLUSION: Many GI fellows lacked confidence and training in key domains of IBD management. Enhancing IBD exposure with didactics and external rotations improved fellows' confidence in specific domains.

Clinical Decision Making in Inflammatory Bowel Disease Mimics: Practice Management from Inflammatory Bowel Disease LIVE.

Background: Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified "IBD-mimics" with consequent clinical management implications. Methods: Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018-February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results: Confirmed IBD cases made up 82.5% (306/371; 193 Crohn's disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions: The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.

Rates, Predictors, and Outcomes of Ustekinumab Dose Escalation in Inflammatory Bowel Disease.

OBJECTIVE: Ustekinumab (UST) is effective for the induction and maintenance of remission in inflammatory bowel disease (IBD). However, a significant proportion of patients will require UST dose escalation. We sought to determine the rates, predictors, and outcomes of UST dose escalation in patients with IBD. PATIENTS AND METHODS: This was a multicenter, retrospective study of all patients with IBD who received UST from January 1, 2014 to March 1, 2022. Primary outcomes were the rates and predictors of UST dose escalation. Secondary outcomes included steroid-free clinical remission, endoscopic healing, and normalization of serum c-reactive protein in patients who underwent UST dose escalation. RESULTS: A total of 198 patients were included (58% females and 76.7% with Crohn's disease). UST dose was escalated by 55.5% (n = 110). Mean baseline albumin was lower in the UST dose escalation group at 3.86 ± 0.47 versus 4.03 ± 0.45 g/dL (P = 0.044). The mean hemoglobin was lower in the UST dose escalation group at 12.1 ± 1.83 versus 12.7 ± 1.42 (P = 0.049). On multivariate analysis, male sex alone was associated with the need for dose escalation (odds ratio: 4.08, 95% CI: 1.20 - 13.90; P = 0.025). In the UST dose escalation group, 66.1% achieved steroid-free clinical remission, 55.8% had normalization of c-reactive protein, and 35.8% achieved endoscopic healing. CONCLUSIONS: UST dose escalation was needed in more than half of patients with IBD in this real-world cohort. UST dose escalation resulted in clinical remission in more than half of the cohort and endoscopic healing in one-third of patients.

Longer Colonoscopy Withdrawal Time Is Associated With the Detection of Visible Dysplasia in Patients With Inflammatory Bowel Disease.

Background: Colonoscopy withdrawal time (CWT) of at least 6-9 minutes is the minimum time needed for adequate adenoma detection in the general population. The ideal CWT in patients with inflammatory bowel disease (IBD) has not been determined. We aimed to identify the optimal CWT associated with the detection of visible dysplasia in patients with IBD. Methods: This is a retrospective study from 1/1/2017 to 9/1/2022 of adult patients with IBD in endoscopic healing undergoing surveillance via high-definition white light colonoscopy. The primary outcome was the association of CWT with visible dysplasia detection. Results: A total of 259 patients (mean age 56 ±â€…14.8 years; 51.3% female, 68% with ulcerative colitis; 8.9% with primary sclerosing cholangitis) underwent 330 colonoscopies. Patients with visible dysplasia were more likely to be older (P < .001) and have a personal history of visible dysplasia (P < .001) and invisible dysplasia (P = .023). The mean CWT was significantly longer in the visible dysplasia group at 26 minutes (interquartile range [IQR] 20-38.5) vs. 21 minutes (IQR 15-28) in procedures without visible dysplasia (P < .001). On multivariable analysis, increased age (P < .001), increased CWT (P = .001), and personal history of visible dysplasia (P = .013) were independently associated with the detection of visible dysplasia. A CWT of ≥15 minutes (odds ratio [OR] 2.71; 95% confidence interval [CI], 1.11-6.6; P = .02] and not ≥9 minutes (OR 2.57; 95% CI, 0.33-20.2; P = .35) is significantly associated with detection of visible dysplasia. Conclusions: For patients with IBD undergoing surveillance via high-definition white light colonoscopy, the mean CWT was independently associated with the detection of visible dysplasia.

Impact of COVID-19 Treatment on Real-World Outcomes in Inflammatory Bowel Disease.

BACKGROUND: While there are multiple safe and effective agents for COVID-19 treatment, their impact in inflammatory bowel disease (IBD) remains uncertain. AIMS: Our objective was to assess the effects of these therapies on both IBD and COVID outcomes. METHODS: A single-center retrospective study of adult patients with IBD who contracted COVID-19 between 12/2020 and 11/2022 was performed. Patients were stratified by COVID-19 treatment (antivirals and/or intravenous antibodies) vs no therapy. The primary outcome was the development of severe COVID-19 infection, defined by need for supplemental oxygen, corticosteroids and/or antibiotics, or hospitalization. Secondary outcomes included rates of withholding advanced IBD therapy (defined as biologic agents or small molecules) and of post-COVID-19 IBD flare. RESULTS: Of 127 patients with COVID-19 infection, 70% were on advanced therapies, 35% received COVID-19 treatment, and 15% developed severe COVID-19. Those treated for COVID-19 were more likely to be on corticosteroids [odds ratio (OR) 4.61, 95% confidence interval (CI) 1.72-12.39, p = 0.002] or advanced IBD therapies (OR 2.78, 95% CI 1.04-7.43, p = 0.041). After adjusting for age, race, sex, corticosteroid use, obesity, COVID-19 vaccination status, and severe COVID-19 infection, those treated for COVID-19 were more likely to have IBD therapy held (OR 6.95, 95% CI 1.72-28.15, p = 0.007). There was no significant difference in rates of post-COVID-19 IBD flares or severe COVID-19 infection. There were no COVID-related deaths. CONCLUSIONS: Patients with IBD on advanced therapies were frequently treated for acute COVID-19. Although COVID-19 treatment was associated with temporary withholding of IBD therapy, it did not result in increased IBD flares.

Ustekinumab Drug Levels and Outcomes in Inflammatory Bowel Disease.

BACKGROUND: Data regarding the utility of therapeutic drug monitoring with ustekinumab (UST) are sparse. Our aim was to determine the correlation of UST levels with outcomes in a cohort of patients with inflammatory bowel disease (IBD). METHODS: This was a multicenter, retrospective study of all patients with IBD who received UST from January 1, 2014 to March 1, 2022. The primary outcomes were the correlation of UST level with clinical remission (per physician global assessment), endoscopic healing [the absence of ulcers/erosions in Crohn's disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC)], and normal serum C-reactive protein (CRP) (≤5 mg/L). Secondary outcomes included defining optimal UST trough levels associated with favorable outcomes. RESULTS: A total of 71 patients (74.6% with CD; 57.7% female) were included. The median age was 39.5 years [interquartile range (IQR): 26 to 52] and 12.6% were on combination therapy with immunomodulators. Median UST trough levels were significantly higher in patients who achieved endoscopic healing at 5.4 µg/mL versus 3.5 µg/mL (P=0.035) and normal CRP at 5.5 µg/mL versus. 3.1 µg/mL (P=0.002). A cutoff UST level of 4.8 µg/mL yielded the highest area under the curve (AUC) of 0.73 (95% CI: 0.61-0.80) to predict a normal CRP followed by a cutoff of 3.5 µg/mL which yielded an AUC of 0.66 (95% CI: 0.52-0.81) to predict endoscopic healing. CONCLUSIONS: UST trough levels were significantly higher in patients who achieved a normal CRP and endoscopic healing. A cutoff UST level of 4.8 µg/mL reliably predicted CRP normalization.

Epstein-Barr virus seroprevalence among inflammatory bowel disease patients in Saudi Arabia.

BACKGROUND: Seroprevalence of Epstein-Barr virus (EBV) in patients with inflammatory bowel disease (IBD) is variable based on geographic distribution. There are no published data on the seroprevalence of EBV in patients with IBD in Saudi Arabia. This study aims to assess the seroprevalence of EBV in patients with IBD in a tertiary center in Saudi Arabia. METHODS: This is a retrospective chart review of patients ≥14 years of age with a confirmed diagnosis of IBD and known EBV status at our institution from January 1, 2018, to January 1, 2023. The primary outcome was the seroprevalence of EBV in IBD. Secondary outcomes included factors associated with EBV seropositivity and rates of EBV seroconversion in originally negative patients. RESULTS: A total of 150 patients were included (74.7% with Crohn's disease, median age 28 years [interquartile range 21-36.3]). EBV non-exposure was noted in 16.8% ( n = 25). The mean age was significantly lower in the EBV-naïve group at 26 ± 8.5 years compared to the EBV-exposed group at 31.2 ± 12.9 years ( P = 0.02). Seroprevalence of EBV was highest in patients >40 years of age (92.9%) and lowest in patients 14-25 years of age (78.2%). The rate of seroconversion in EBV-naïve patients was 16.7% after a mean follow-up time of 47.9 ± 46.3 months. CONCLUSION: In our cohort of IBD patients, 16.8% were naïve to EBV, and young age was a significant predictor of EBV non-exposure. Our data supports the practice of assessing EBV before initiating thiopurine therapy since EBV seroprevalence is not universal in our population.

Saudi consensus guidance for the management of inflammatory bowel disease during pregnancy.

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

ScRNA-seq defines dynamic T-cell subsets in longitudinal colon and peripheral blood samples in immune checkpoint inhibitor-induced colitis.

Immune checkpoint inhibitors (ICIs) are increasingly being used to manage multiple tumor types. Unfortunately, immune-related adverse events affect up to 60% of recipients, often leading to treatment discontinuation in settings where few alternative cancer therapies may be available. Checkpoint inhibitor induced colitis (ICI-colitis) is a common toxicity for which the underlying mechanisms are poorly defined. To better understand the changing colon-specific and peripheral immune environments over the course of progression and treatment of colitis, we collected blood and colon tissue from a patient with Merkel cell carcinoma who developed colitis on treatment with pembrolizumab. We performed single-cell RNA sequencing and T-cell receptor sequencing on samples collected before, during and after pembrolizumab and after various interventions to mitigate toxicity. We report T-cells populations defined by cytotoxicity, memory, and proliferation markers at various stages of colitis. We show preferential depletion of CD8+ T cells with biologic therapy and nominate both circulating and colon-resident T-cell subsets as potential drivers of inflammation and response to immune suppression. Our findings highlight the need for further exploration of the colon immune environment and rationalize future studies evaluating biologics for ICI-colitis, including in the context of ICI re-challenge.

Use of Standardized Inflammatory Bowel Disease Endoscopy Scores in Clinical Practice.

Background: Inflammatory bowel disease (IBD) treatment targets include mucosal healing based on standardized endoscopic scoring systems. The rates and ease of use of these scoring systems in practice have not been well described. We aimed to assess the rates and factors associated with the use of IBD endoscopic scoring systems in practice from IBD LIVE attendees. Methods: IBD Live is an international case-based conference focusing on the management of patients with IBD. We created a web-based survey consisting of 38 questions on the frequency and ease of use of various IBD endoscopic scores. This survey was emailed to the IBD Live listserv in March 2022 with a second email sent 14 days later. We included only respondents who are currently performing endoscopy. Continuous variables were analyzed using an unpaired student's t-test. Categorical variables were analyzed using Pearson's chi-square test. Results: There were 65 responses out of 170 (38.2% response rate) regular attendees. Eleven responses were excluded (4 with no response on the use of endoscopy scores, and 7 were not performing endoscopy). Of the respondents, 72.2% are from the United States, 70.4% are adult gastroenterologists, 53.9% in academic practice, and 40.7% in practice for ≥15 years. Of the endoscopy scores used ≥50% of the time, 74.1% were using the Mayo Endoscopic Subscore (MES), 72.3% using the Rutgeerts Score, 61.2% using the Simple Endoscopic Score for Crohn's Disease, and 28.6% using the Pouchitis Disease Activity Index. Attending IBD LIVE ≥ monthly (P = .028), attending an IBD conference at least every 2 years (P = .020), and having the scoring system incorporated into the endoscopy documentation software (P = .002) were associated with more consistent use of the MES. Attending IBD Live at least monthly (P = .026), having an IBD volume of ≥50% (P = .011), and attending an IBD conference at least every 2 years (P = .004) was associated with more frequent use of the Rutgeerts score. There were no factors that increased the use of other endoscopic scores. Conclusions: The MES and the Rutgeerts score are more commonly used with much lower rates of use of endoscopic scores for Crohn's disease and pouchitis. The use of these endoscopy scores is more common among those who regularly attend IBD conferences, have higher volume IBD practices, and have these scoring systems incorporated into endoscopy software. Further evaluation of barriers to use and ways to improve utilization of endoscopic scoring for Crohn's disease and pouchitis is needed.

Emerging Therapies for Ulcerative Colitis: Updates from Recent Clinical Trials.

Ulcerative colitis (UC) is a chronic and progressive inflammatory disorder that affects the colon. The advent of advanced therapies such as biologic agents and small molecules has revolutionized the management of UC. Despite the expanding therapeutic armamentarium of advanced therapies to treat UC, the overall net remission rates and durability of currently available agents are relatively low. This highlights the need for further drug development and more innovative clinical trial design. There are currently multiple emerging agents in the pipeline for the management of UC. This includes agents with alternative routes of administration such as oral or subcutaneous tumor necrosis factor inhibitors or novel mechanisms of action such as toll-like receptor 9 (TLR9) agonist cobitolimod and phosphodiesterase 4 inhibitor apremilast. In this review, we will highlight novel and emerging advanced therapies currently in the pipeline for the management of UC.

Outcomes of Infliximab-Treated inflammatory bowel disease patients undergoing therapeutic drug monitoring with two different assays.

OBJECTIVES: There are multiple assays for infliximab (IFX) drug level (IFX-DL) and antibody to infliximab (ATI) measurement. The aims of this study are to examine the correlation and outcomes of IFX-DL and ATI in inflammatory bowel disease (IBD) patients, simultaneously measured with different methods in different institutions. DESIGN AND METHODS: Residual samples of IFX-treated IBD patients undergoing drug monitoring for IFX-DL and ATI, both measured by ECLIA (Esoterix Laboratories) were used to simultaneously quantify IFX-DL via LC-MS/MS and ATI via an in-house ECLIA (ih-ECLIA) (Mayo Clinic Laboratories). Comparisons of IFX-DL and ATI detection between the assays from different institutions were performed, along with a comparison between the assays by association of IFX-DL and ATI obtained by each method with clinical remission, endoscopic healing (EH) and normal serum C-reactive protein (CRP ≤ 8 mg/L). RESULTS: A total of 151 patients were included (median age, 32 years (range, 12-84); 45.7% female). The median IFX-DL was 7 mcg/mL (IQR: 1.3, 19.4) and 6 mcg/mL (IQR: 0.9, 20) via LC-MS/MS and ECLIA, respectively (Spearman correlation coefficient r = 0.97). ATI was detected in 13/142 (9.2%) via ih-ECLIA of whom 100% had IFX-DL < 5 mcg/mL by LC-MS/MS. ATI was positive in 39/151 (25.8%) via ECLIA, and 84.6% of positives had IFX-DL < 5 mcg/mL by ECLIA. Compared to ECLIA, the frequency of ATI detection via ih-ECLIA was lower in patients in clinical remission (7.3% vs 36.6%; p = 0.0005), those with normal CRP (5.9% vs. 20.0%; p = 0.0005), and in patients with EH (5.3% vs 18.4%; p = 0.03). CONCLUSIONS: IFX-DL was comparable between LC-MS/MS and ECLIA assays. Rate of ATI detection via ih-ECLIA was lower than ECLIA, which was more aligned with favorable clinical outcomes.

Early Flexible Sigmoidoscopy Improves Clinical Outcomes in Acute Severe Ulcerative Colitis.

Objectives: Guidelines recommend performing a flexible sigmoidoscopy in patients hospitalized with acute severe ulcerative colitis (ASUC). However, it is unclear if time to sigmoidoscopy affects relevant clinical outcomes. We aimed to assess the impact of early sigmoidoscopy on clinical outcomes using a well-characterized cohort of patients with ASUC. Methods: This is a single-center, retrospective study of all patients hospitalized with ASUC from January 1, 2012 to November 1, 2021. Early sigmoidoscopy was defined as occurring within 72 hours of admission while delayed sigmoidoscopy was defined as occurring >72 hours after admission. Primary outcomes were cumulative days of intravenous (IV) corticosteroid (CS) use, length of hospital stay, and colectomy rates. Secondary outcomes were time to infliximab (IFX) rescue and inpatient opioid medication use. Results: A total of 112 patients hospitalized with ASUC who underwent sigmoidoscopy were included in the analysis. Eighty-seven patients (78%) had early sigmoidoscopy and 25 (22%) had delayed sigmoidoscopy. Patients in the early sigmoidoscopy group were exposed to significantly fewer days of IV CS (4.5 vs 9.2 days; P < .001), had shorter hospital stays (6.4 vs 19.3 days; P < .001), and shorter time to IFX rescue (3.5 vs 6.4 days; P = .004). Rates of colectomy in the early and delayed sigmoidoscopy groups were 17% versus 28%, respectively (P = .23). Longer time to sigmoidoscopy was associated with a 16% increased risk of colectomy (HR = 1.16, P = .002). Conclusions: In this well-characterized cohort, early sigmoidoscopy in ASUC was associated with favorable clinical outcomes. These findings highlight the benefits of early sigmoidoscopy in patients with ASUC. Larger prospective studies are needed to corroborate these findings.

Oral Vancomycin Induced and Maintained Clinical and Endoscopic Remission in Ulcerative Colitis and Primary Sclerosing Cholangitis Post-liver Transplantation.

We present a case of a 34-year-old man with primary sclerosing cholangitis and associated ulcerative colitis refractory to multiple advanced therapies who achieved clinical and endoscopic remission with oral vancomycin therapy.

Assessment of Inflammatory Bowel Disease Training Among Gastroenterology Fellows.

In this multicenter survey study, we found that many gastroenterology fellows lacked confidence and desired a "moderate to a lot more" training in important inflammatory bowel disease management domains.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

Impact of thiopurine dose in anti-tumor necrosis factor combination therapy on outcomes in inflammatory bowel disease.

Background: Combination therapy with thiopurines and anti-tumor necrosis factor (TNF) is superior to monotherapy in Crohn's disease (CD) and ulcerative colitis (UC). The optimal dose of thiopurines in combination therapy remains unclear. We investigated the impact of thiopurine dose in combination therapy on outcomes in inflammatory bowel disease (IBD). Methods: This was a single-center, retrospective study of patients with IBD treated with thiopurine and anti-TNF combination therapy between 1/2012 and 11/2020. A therapeutic dose of thiopurines was defined as ≥1 mg/kg for 6-mercaptopurine and ≥2 mg/kg for azathioprine. The primary outcome was anti-drug antibody (ADA) formation in patients on a therapeutic thiopurine dose vs. a lower thiopurine dose group. Secondary outcomes included steroid-free clinical remission, endoscopic healing (absence of ulcers/erosions in CD and Mayo endoscopic score ≤1 for UC), and normal serum C-reactive protein (CRP) in patients who were on combination therapy. Results: A total of 108 patients were included (median age 31.5 years; 58.3% male). A therapeutic dose of thiopurine was used in 19%. In the therapeutic thiopurine dose group, 23.8% developed ADA vs. 29.9% (P=0.58) in the lower dose group. No significant differences were noted between the therapeutic and lower dose thiopurine groups in terms of steroid-free clinical remission (57.1% vs. 60.9%, P=0.75), endoscopic healing (55% vs. 60%, P=0.69), and normal CRP (52.4% vs. 52.9%, P=0.27). Conclusion: In our cohort of patients with IBD on anti-TNF combination therapy, thiopurine dose was not associated with significant differences in anti-TNF immunogenicity and clinical outcomes.