Considerations in gender-affirming hormone therapy in transgender and gender diverse patients undergoing liver transplantation.

Liver transplantation is lifesaving for patients with end-stage liver disease. Similar to the role of transplantation for patients with end-stage liver disease, gender-affirming hormone therapy (GAHT) can be lifesaving for transgender and gender diverse (TGGD) patients who experience gender dysphoria. However, management of such hormone therapy during the perioperative period is unknown and without clear guidelines. Profound strides can be made in improving care for TGGD patients through gender-affirming care and appropriate management of GAHT in liver transplantation. In this article, we call for the transplant community to acknowledge the integral role of GAHT in the care of TGGD liver transplant candidates and recipients. We review the current literature and describe how the transplant community is ethically obligated to address this health care gap. We suggest tangible steps that clinicians may take to improve health outcomes for this minoritized patient population.

A Population-Based Matched Cohort Study of Digestive System Cancer Incidence and Mortality in Individuals With and Without Inflammatory Bowel Disease.

INTRODUCTION: To study digestive system cancer risks in inflammatory bowel diseases (IBD) in the biologic era. METHODS: We used population-level administrative and cancer registry data from Ontario, Canada (1994 - 2020) to compare people with IBD to matched controls (1:10 by sex and birth year) on trends in age-sex standardized cancer incidence and risk ratios of incident cancers and cancer-related deaths. RESULTS: Among 110,919 IBD and 1,109,190 controls, colorectal cancer (CRC) incidence (per 100,000 person-years) declined similarly in people with ulcerative colitis (average annual percentage change (AAPC) -1.81; 95% CI, -2.48, -1.156) and controls (AAPC -2.79; 95% CI, -3.44, -2.14), while small bowel cancer incidence rose faster in those with Crohn's disease (AAPC 9.68; 95% CI, 2.51, 17.3) than controls (AAPC 3.64; 95% CI, 1.52, 5.80). Extra-intestinal digestive cancer incidence rose faster in people with IBD (AAPC 3.27; 95% CI, 1.83, 4.73) than controls (AAPC -1.87; 95% CI, -2.33, -1.42), particularly for liver (IBD AAPC 8.48; 95% CI, 4.11, 13.1) and bile duct (IBD AAPC 7.22; 95 % CI, 3.74, 10.8) cancers. Beyond 2010, the incidences (and respective mortality rates) of colorectal (1.60; 95% CI, 1.46, 1.75), small bowel (4.10; 95% CI 3.37, 4.99), bile duct (2.33; 95% CI 1.96, 2.77) and pancreatic (1.19; 95% CI, 1.00, 1.40) cancers, were higher in people with IBD. DISCUSSION: Cancer incidence is declining for CRC and rising for other digestive cancers in people with IBD. Incidence and mortality remain higher in IBD than controls for colorectal, small bowel, bile duct and pancreatic cancers.

Forecasting the Incidence and Prevalence of Inflammatory Bowel Disease: A Canadian Nationwide Analysis.

INTRODUCTION: Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade. METHODS: Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence. RESULTS: The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81). DISCUSSION: Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population.

Hormonal Contraceptives Reduce Active Symptomatic Disease but May Increase Intestinal Inflammation in IBD.

BACKGROUND: Among women of reproductive age with inflammatory bowel disease (IBD), we aimed to assess the relationship of hormonal contraceptives (HCs) with IBD-related symptoms, and intestinal inflammation. METHODS: A nested cohort of women in the longitudinal Manitoba Living with IBD Study, ages 18 to 49, were followed for 1 year, with bi-weekly online surveys. This included a validated measure of disease activity; IBD Symptom Inventory (IBDSI), and stool samples obtained at 3 time-points for assessment of fecal calprotectin (FCAL). Use of HC included oral and vaginal intrauterine devices. Logistic regression analysis was used to assess the association between HC and IBD-related symptoms (IBDSI>14 for Crohn disease, >13 for ulcerative colitis), or inflammation (FCAL>250 ug/g) at any measurement point in the study. RESULTS: Of 71 women, 17 (24%) reported taking HC in the 1 year period. Adjusting for age, disease type, disease duration, and smoking status, the odds of having increased IBD-related symptoms (IBDSI) during the year were lower for women using HC compared with women not using HC [adjusted odds ratio 0.16, 95% CI, 0.02-0.90]. Conversely, women using HC were more likely to have inflammation during the year [adjusted odds ratio 5.7, 95% CI, 1.23-43.6]. CONCLUSIONS: HC use among women with IBD was associated with a lower likelihood of IBD-related symptoms but a higher likelihood of experiencing intestinal inflammation (FCAL>250 ug/g) over 1 year. Further work is needed to examine this dichotomous result, potentially examining aspects such as duration of HC use, and the types of HC.

AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review.

DESCRIPTION: Proton pump inhibitors (PPIs) are among the most commonly used medications in the world. Developed for the treatment and prevention of acid-mediated upper gastrointestinal conditions, these agents are being used increasingly for indications where their benefits are less certain. PPI overprescription imposes an economic cost and contributes to polypharmacy. In addition, PPI use has been increasingly linked to a number of adverse events (PPI-associated adverse events [PAAEs]). Therefore, de-prescribing of PPIs is an important strategy to lower pill burden while reducing real costs and theoretical risks. The purpose of this clinical update was to provide Best Practice Advice (BPA) statements about how to approach PPI de-prescribing in ambulatory patients. METHODS: Our guiding principle was that, although PPIs are generally safe, patients should not use any medication when there is not a reasonable expectation of benefit based on scientific evidence or prior treatment response. Prescribers are responsible for determining whether PPI use is absolutely or conditionally indicated and, when uncertainty exists, to incorporate patient perspectives into PPI decision making. We collaboratively outlined a high-level "process map" of the conceptual approach to de-prescribing PPIs in a clinical setting. We identified the following 3 key domains that required BPA guidance: documentation of PPI indication; identifying suitable candidates for consideration of de-prescribing; and optimizing successful de-prescribing. Co-authors drafted 1 or more potential BPAs, supported by literature review, for each domain. All co-authors reviewed, edited, and selected or rejected draft BPAs for inclusion in the final list submitted to the American Gastroenterological Association Governing Board. Because this was not a systematic review, we did not carry out a formal rating of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient's primary care provider. BEST PRACTICE ADVICE 2: All patients without a definitive indication for chronic PPI should be considered for trial of de-prescribing. BEST PRACTICE ADVICE 3: Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI. BEST PRACTICE ADVICE 4: Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation. BEST PRACTICE ADVICE 5: Patients with known Barrett's esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing. BEST PRACTICE ADVICE 6: PPI users should be assessed for upper gastrointestinal bleeding risk using an evidence-based strategy before de-prescribing. BEST PRACTICE ADVICE 7: Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing. BEST PRACTICE ADVICE 8: Patients who discontinue long-term PPI therapy should be advised that they may develop transient upper gastrointestinal symptoms due to rebound acid hypersecretion. BEST PRACTICE ADVICE 9: When de-prescribing PPIs, either dose tapering or abrupt discontinuation can be considered. BEST PRACTICE ADVICE 10: The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PAAEs. The presence of a PAAE or a history of a PAAE in a current PPI user is not an independent indication for PPI withdrawal. Similarly, the presence of underlying risk factors for the development of an adverse event associated with PPI use should also not be an independent indication for PPI withdrawal.

Perianal Fistulas Are Associated with Persistently Higher Direct Health Care Costs in Crohn's Disease: A Population-Based Study.

BACKGROUND: The economic impact of perianal fistulas in Crohn's disease (CD) has not been formally assessed in population-based studies in the biologic era. AIM: To compare direct health care costs in persons with and without perianal fistulas. METHODS: We performed a longitudinal population-based study using administrative data from Ontario, Canada. Adults (> 17 years) with CD were identified between 2007 and 2013 using validated algorithms. Perianal fistula positive "cases" were matched to up to 4 "controls" with CD without perianal fistulas based on age, sex, geographic region, year of CD diagnosis and duration of follow-up. Direct health care costs, excluding drug costs from private payers, were estimated annually beginning 5 years before (lookback) and up to 9 years after perianal fistula diagnosis (study completion) for cases and a standardized date for matched controls. RESULTS: A total of 581 cases were matched to 1902 controls. The annual per capita direct cost for cases was similar at lookback compared to controls ($2458 ± 6770 vs $2502 ± 10,752; p = 0.952), maximally greater in the first year after perianal fistulas diagnosis ($16,032 ± 21,101 vs $6646 ± 13,021; p < 0.001) and remained greater at study completion ($11,358 ± 17,151 vs $5178 ± 9792; p < 0.001). At perianal fistula diagnosis, the cost difference was driven primarily by home care cost (tenfold greater), publicly-covered prescription drugs (threefold greater) and hospitalizations (twofold greater), whereas at study completion, prescription drugs were the dominant driver (threefold greater). CONCLUSION: In our population-based cohort, perianal fistulas were associated with significantly higher direct healthcare costs at the time of perianal fistulas diagnosis and sustained long-term.

Earlier Anti-TNF Initiation Leads to Long-term Lower Health Care Utilization in Crohn's Disease but Not in Ulcerative Colitis.

BACKGROUND & AIMS: The timing of initiating biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC) is an area of ongoing controversy. In particular, there is concern that delaying the initiation of biologic therapy may lead to more treatment-resistant disease, which can result in more complications and hospitalizations. METHODS: We used health administrative data from Manitoba, Canada to identify all persons with a new diagnosis of inflammatory bowel disease (IBD) between 2001 and 2018 who received tumor necrosis factor antagonists (anti-TNF) therapy and had at least 1 year of post anti-TNF initiation follow-up. We measured the rates of hospitalization, surgery, and outpatient visits, prior to and for up to 5 years following anti-TNF initiation. We compared the rates of these health care utilization outcomes between persons receiving anti-TNFs within 2 years following diagnosis and those receiving anti-TNFs more than 2 years following IBD diagnosis. We used inverse probability treatment weighting to adjust for baseline differences in risk between the 2 groups. RESULTS: Among 742 persons with CD, early anti-TNF initiators had fewer IBD-specific and overall hospitalizations over the 5 years following the start of therapy. Incidence of resective surgery was also lower in earlier anti-TNF initiators with CD if the first year following initiation was excluded from the analysis. In 318 cases of UC, there was no impact of the timing of anti-TNF therapy on the rates of hospitalization and surgery. CONCLUSIONS: Earlier administration of anti-TNF therapy is associated with reduced downstream health care resource utilization in CD, though these impacts are not evident in UC.

Hospitalization With Clostridioides difficile in Pediatric Inflammatory Bowel Disease: a Population-Based Study.

OBJECTIVES: Several studies have demonstrated higher rates of Clostridioides difficile infection (CDI) in adults with inflammatory bowel disease (IBD). We conducted a population-based study comparing the risk of hospitalization with CDI in children with and without IBD. METHODS: Using health administrative data and validated algorithms, we identified all children (<16 years) diagnosed with IBD in 5 Canadian provinces, then age and sex matched to 5 children without IBD. Province-specific 5-year incidence rates of hospitalization with CDI were pooled and generalized linear mixed-effects models were used to estimate the crude incidence rate ratio (IRR) comparing (1) children with and without IBD and (2) children with Crohn disease and ulcerative colitis. Hazard ratios (HR) from Cox proportional hazards models adjusting for age, sex, rural/urban household, and income were pooled using fixed-effects models. RESULTS: The incidence rate of CDI identified during hospitalization was 49.06 [95% confidence interval (CI), 39.40-61.08] per 10,000 person-years (PY) in 3593 children with IBD compared to 0.39 (95% CI, 0.13-1.21) per 10,000 PY in 16,284 children without IBD (crude IRR, 133.4, 95% CI, 42.1-422.7; adjusted HR, 68.2, 95% CI, 24.4-190.4). CDI was identified less often in children with Crohn disease than ulcerative colitis (crude IRR, 0.51, 95% CI, 0.32-0.82; adjusted HR, 0.69, 95% CI, 0.46-1.05). CONCLUSIONS: Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI.

Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study.

OBJECTIVE: The microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear. DESIGN: Here, we rank the size effect of disease activity, medications, diet and geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in patients with Crohn's disease (CD; n=303), ulcerative colitis (UC; n = 228) and controls (n=161), followed longitudinally (at three time points with 16 weeks intervals). RESULTS: Reduced microbiota diversity but increased variability was confirmed in CD and UC compared with controls. Significant compositional differences between diseases, particularly CD, and controls were evident. Longitudinal analyses revealed reduced temporal microbiota stability in IBD, particularly in patients with changes in disease activity. Machine learning separated disease from controls, and active from inactive disease, when consecutive time points were modelled. Geographic location accounted for most of the microbiota variance, second to the presence or absence of CD, followed by history of surgical resection, alcohol consumption and UC diagnosis, medications and diet with most (90.3%) of the compositional variance stochastic or unexplained. CONCLUSION: The popular concept of precision medicine and rational design of any therapeutic manipulation of the microbiota will have to contend not only with the heterogeneity of the host response, but also with widely differing lifestyles and with much variance still unaccounted for.

Anxiety and Depression Leads to Anti-Tumor Necrosis Factor Discontinuation in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Anxiety and mood disorders (AMDs) are common among persons with inflammatory bowel diseases (IBD) and are associated with increased health care use and lower quality of life. We assessed the effects of AMDs on persistence on anti-tumor necrosis factor (anti-TNF) therapy in patients with IBD, and risk of IBD-related adverse outcomes after therapy initiation. METHODS: We identified all persons with IBD in Manitoba, Canada who were dispensed an anti-TNF agent from 2001 through 2016 and then identified those with a validated administrative definition of AMD in the 2 years before initiation of therapy. Survival analysis was used to assess the association between active AMDs and anti-TNF discontinuation and the first occurrence of an IBD-related adverse outcome (defined as IBD-related hospitalization or surgery, new or recurrent corticosteroid use, switching to an alternative anti-TNF, or death). We used Cox proportional hazards multivariable regression models to adjust for demographic and clinical factors associated with outcomes. RESULTS: We identified 1135 persons with IBD who began anti-TNF therapy; 178 of these patients (15.7%) met the diagnostic criteria for an AMD. AMDs significantly increased risk of discontinuation of anti-TNF therapy (adjusted hazard ratio, 1.28; 95% CI, 1.03-1.59) and discontinuation in the 1 year following anti-TNF initiation (hazard ratio, 1.50; 95% CI, 1.15-1.94). There was no association between AMDs and subsequent risk of IBD-related adverse events. CONCLUSIONS: Patients with IBD and an AMD within 2 years before starting anti-TNF therapy are at increased risk of discontinuing therapy, compared to patients with IBD without AMD. Studies are needed to determine if treatment of AMDs increases compliance with treatment.

Trends in Corticosteroid Use During the Era of Biologic Therapy: A Population-Based Analysis.

INTRODUCTION: Corticosteroids are effective for inducing clinical remission in inflammatory bowel disease (IBD), but not for maintaining remission. Reducing corticosteroid use and dependence is an important treatment goal since their use is associated with adverse events. The extent to which the improvements in IBD therapy have led to less corticosteroid use in the modern era remains unclear. METHODS: We used the University of Manitoba Inflammatory Bowel Disease Epidemiologic Database to assess the cumulative annual dosing of corticosteroids on a per-patient basis for all persons with IBD in the province of Manitoba between 1997 and 2017. Joinpoint analysis was used to assess for trends in corticosteroid use and to look at variation in the trends over time. RESULTS: The mean annual exposure to corticosteroids decreased from 419 mg/yr (1997) to 169 mg/yr (2017) for Crohn's disease (CD) (annual decline: 3.8% per year, 95% confidence interval 3.1-4.6) and from 380 to 240 mg/yr in ulcerative colitis (UC) (annual decline: 2.5% per year, 95% confidence interval 2.1-2.8). In CD, there was an acceleration in the rate of decline after 2007 (pre-2007, 1.9% decline per year; after 2007, 5.7% per year); there was no corresponding acceleration in the rate of decline in UC. DISCUSSION: Corticosteroid use has decreased in both CD and UC over the past 2 decades, becoming more pronounced after 2007 in CD. Potential explanations include introduction and increasing penetrance of biologic therapy in CD and greater awareness of corticosteroid-related adverse events in IBD. Further work is required understand the drivers of persistent corticosteroid use in IBD and how this can be further reduced.

Dose Augmentation of Tumor Necrosis Factor Inhibitors is Frequently Performed in Persons With Inflammatory Bowel Disease in the Absence of Objective Evidence of Active Inflammation.

BACKGROUND: Antitumor necrosis factor (anti-TNF) dose augmentation is frequently utilized in the management of inflammatory bowel disease (IBD), yet the extent to which clinicians assess for objective markers of inflammation before using the strategy is unknown. AIMS: To determine the incidence of anti-TNF dose augmentation and the frequency with which it is preceded by the objective assessment of IBD activity. MATERIALS AND METHODS: All 23 prescribers of anti-TNF for IBD in Manitoba facilitated chart review of their adult anti-TNF users from 2005 to 2016. Time from anti-TNF initiation to dose augmentation was recorded for all previously biologic-naïve patients. The practices of 11 of 23 prescribers were audited in greater detail and the biochemical, imaging, and endoscopic investigations conducted in the 90-day preceding dose augmentation extracted. RESULTS: A total of 838 patients met inclusion criteria; 70.4% had Crohn's disease, whereas 29.6% had ulcerative colitis or IBD unclassified. The median duration of follow-up was 22.6 [interquartile range (IQR), 10.3-43.2] months for adalimumab and 28.4 (IQR, 10.2-59.9) months for infliximab (P=0.01). The cumulative incidence of dose augmentation at 12 months was 32.9%. Dose augmentation occurred more often in ulcerative colitis than in Crohn's disease (hazard ratio, 1.83; IQR, 1.36-2.47). Overall, 70.7% of patients underwent some form of testing to assess the inflammatory burden before dose augmentation. Objective evidence of inflammation supporting dose augmentation was documented in only 24.7% of cases. CONCLUSIONS: One third of previously biologic-naïve patients had anti-TNF doses increased within the first 12 months of treatment. Dose augmentation frequently occurred in the absence of objective evidence of inflammatory disease activity.

Events Within the First Year of Life, but Not the Neonatal Period, Affect Risk for Later Development of Inflammatory Bowel Diseases.

BACKGROUND & AIMS: We performed a population-based study to determine whether there was an increased risk of inflammatory bowel diseases (IBD) in persons with critical events at birth and within 1 year of age. METHODS: We collected data from the University of Manitoba IBD Epidemiology Database, which contains records on all Manitobans diagnosed with IBD from 1984 through 2010 and matched controls. From 1970 individuals' records can be linked with those of their mothers, so we were able to identify siblings. All health care visits or hospitalizations during the neonatal and postnatal periods were available from 1970 through 2010. We collected data on infections, gastrointestinal illnesses, failure to thrive, and hospital readmission in the first year of life and sociodemographic factors at birth. From 1979, data were available on gestational age, Apgar score, neonatal admission to the intensive care unit, and birth weight. We compared incident rate of infections, gastrointestinal illnesses, and failure to thrive between IBD cases and matched controls as well as between IBD cases and siblings. RESULTS: Data on 825 IBD cases and 5999 matched controls were available from 1979. Maternal diagnosis of IBD was the greatest risk factor for IBD in offspring (odds ratio [OR], 4.53; 95% confidence interval [CI], 3.08-6.67). When we assessed neonatal events, only being in the highest vs lowest socioeconomic quintile increased risk for later development of IBD (OR, 1.35; 95% CI, 1.01-1.79). For events within the first year of life, being in the highest socioeconomic quintile at birth and infections (OR, 1.39; 95% CI, 1.09-1.79) increased risk for developing IBD at any age. Infection in the first year of life was associated with diagnosis of IBD before age 10 years (OR, 3.06; 95% CI, 1.07-8.78) and before age 20 years (OR, 1.63; 95% CI, 1.18-2.24). Risk for IBD was not affected by gastrointestinal infections, gastrointestinal disease, or abdominal pain in the first year of life. CONCLUSIONS: In a population-based study, we found infection within the first year of life to be associated with a diagnosis of IBD. This might be due to use of antibiotics or a physiologic defect at a critical age for gut microbiome development.

Past and Future Burden of Inflammatory Bowel Diseases Based on Modeling of Population-Based Data.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) exist worldwide, with high prevalence in North America. IBD is complex and costly, and its increasing prevalence places a greater stress on health care systems. We aimed to determine the past current, and future prevalences of IBD in Canada. METHODS: We performed a retrospective cohort study using population-based health administrative data from Alberta (2002-2015), British Columbia (1997-2014), Manitoba (1990-2013), Nova Scotia (1996-2009), Ontario (1999-2014), Quebec (2001-2008), and Saskatchewan (1998-2016). Autoregressive integrated moving average regression was applied, and prevalence, with 95% prediction intervals (PIs), was forecasted to 2030. Average annual percentage change, with 95% confidence intervals, was assessed with log binomial regression. RESULTS: In 2018, the prevalence of IBD in Canada was estimated at 725 per 100,000 (95% PI 716-735) and annual average percent change was estimated at 2.86% (95% confidence interval 2.80%-2.92%). The prevalence in 2030 was forecasted to be 981 per 100,000 (95% PI 963-999): 159 per 100,000 (95% PI 133-185) in children, 1118 per 100,000 (95% PI 1069-1168) in adults, and 1370 per 100,000 (95% PI 1312-1429) in the elderly. In 2018, 267,983 Canadians (95% PI 264,579-271,387) were estimated to be living with IBD, which was forecasted to increase to 402,853 (95% PI 395,466-410,240) by 2030. CONCLUSION: Forecasting prevalence will allow health policy makers to develop policy that is necessary to address the challenges faced by health systems in providing high-quality and cost-effective care.

Effectiveness of Dose De-escalation of Biologic Therapy in Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: De-escalation of biologic therapy is a commonly encountered clinical scenario. Although biologic discontinuation has been associated with high rates of relapse, the effectiveness of dose de-escalation is unclear. This review was performed to determine the effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception to October 2019. Randomized controlled trials and observational studies involving dose de-escalation of biologic therapy in adults with inflammatory bowel disease in remission were included. Studies involving biologic discontinuation only and those lacking outcomes after dose de-escalation were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: We identified 1,537 unique citations with 20 eligible studies after full-text review. A total of 995 patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial. Seven studies included patients with Crohn's disease, 1 included patients with ulcerative colitis, and 12 included both. Overall, clinical relapse occurred in 0%-54% of patients who dose de-escalated biologic therapy (17 studies). The 1-year rate of clinical relapse ranged from 7% to 50% (6 studies). Eighteen studies were considered at high risk of bias, mostly because of the lack of a control group. DISCUSSION: Dose de-escalation seems to be associated with high rates of clinical relapse; however, the quality of the evidence was very low. Additional controlled prospective studies are needed to clarify the effectiveness of biologic de-escalation and identify predictors of success.

Longitudinal Trends in the Direct Costs and Health Care Utilization Ascribable to Inflammatory Bowel Disease in the Biologic Era: Results From a Canadian Population-Based Analysis.

OBJECTIVES: The prevalence of inflammatory bowel disease (IBD) is increasing. The total direct costs of IBD have not been assessed on a population-wide level in the era of biologic therapy. DESIGN: We identified all persons with IBD in Manitoba between 2005 and 2015, with each matched to 10 controls on age, sex, and area of residence. We enumerated all hospitalizations, outpatient visits and prescription medications including biologics, and their associated direct costs. Total and per capita annual IBD-attributable costs and health care utilization (HCU) were determined by taking the difference between the costs/HCU accrued by an IBD case and their controls. Generalized linear modeling was used to evaluate trends in direct costs and Poisson regression for trends in HCU. RESULTS: The number of people with IBD in Manitoba increased from 6,323 to 7,603 between 2005 and 2015. The total per capita annual costs attributable to IBD rose from $3,354 in 2005 to $7,801 in 2015, primarily driven by an increase in per capita annual anti-tumor necrosis factor costs, which rose from $181 in 2005 to $5,270 in 2015. There was a significant decline in inpatient costs for CD ($99 ± 25/yr. P < 0.0001), but not for ulcerative colitis ($8 increase ±$18/yr, P = 0.63). DISCUSSION: The direct health care costs attributable to IBD have more than doubled over the 10 years between 2005 and 2015, driven mostly by increasing expenditures on biological medications. IBD-attributable hospitalization costs have declined modestly over time for persons with CD, although no change was seen for patients with ulcerative colitis.

Inflammatory bowel disease and new-onset psychiatric disorders in pregnancy and post partum: a population-based cohort study.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) have an elevated risk of mental illness. We determined the incidence and correlates of new-onset mental illness associated with IBD during pregnancy and post partum. DESIGN: This cohort study using population-based health administrative data included all women with a singleton live birth in Ontario, Canada (2002-2014). The incidence of new-onset mental illness from conception to 1-year post partum was compared between 3721 women with and 798 908 without IBD, generating adjusted HRs (aHR). Logistic regression was used to identify correlates of new-onset mental illness in the IBD group. RESULTS: About 22.7% of women with IBD had new-onset mental illness versus 20.4% without, corresponding to incidence rates of 150.2 and 132.8 per 1000 patient-years (aHR 1.12, 95% CI 1.05 to 1.20), or one extra case of new-onset mental illness per 43 pregnant women with IBD. The risk was elevated in the post partum (aHR 1.20, 95% CI 1.09 to 1.31), but not during pregnancy, and for Crohn's disease (aHR 1.12, 95% CI 1.02 to 1.23), but not ulcerative colitis. The risk was specifically elevated for a new-onset mood or anxiety disorder (aHR 1.14, 95% CI 1.04 to 1.26) and alcohol or substance use disorders (aHR 2.73, 95% CI 1.42 to 5.26). Predictors of a mental illness diagnosis were maternal age, delivery year, medical comorbidity, number of prenatal visits, family physician obstetrical care and infant mortality. CONCLUSION: Women with IBD were at an increased risk of new-onset psychiatric diagnosis in the postpartum period, but not during pregnancy. Providers should look to increase opportunities for prevention, early identification and treatment accordingly.