Adherence to endoscopic surveillance guidelines for patients with inflammatory bowel disease: An Australian cohort study.

BACKGROUND AND AIM: Patients with inflammatory bowel disease have an increased risk of developing colorectal cancer as compared with the general population. Endoscopic surveillance to detect early dysplastic changes is advised by several published clinical guidelines, which provide recommendations as to the timing and performance of surveillance procedures. There is a paucity of data as to adherence with these guidelines in clinical practice. METHODS: A longitudinal inception cohort study of all new patients diagnosed with inflammatory bowel disease across a service network of Australian hospitals between January 2005 and June 2014, with continuous follow-up in a gastroenterology clinic until December 31, 2022. Patients were included if they warranted surveillance according to the Australian guidelines. Adherence to guidelines and technical and quality measures were reported. RESULTS: A total of 136 patients were included, and a total of 263 surveillance procedures were performed. Ninety-five patients (70%) had their first surveillance colonoscopy within the correct time interval. Fifty patients (37%) were completely adherent to guidelines with respect to timing of all surveillance procedure. The overall dysplasia detection rate for surveillance procedures was 10%. Chromoendoscopy was only performed in 16% of procedures. CONCLUSIONS: Adherence to endoscopic surveillance guidelines with regard to timing of procedures and the utilization of chromoendoscopy is poor. Further clinician education, promotion of the surveillance guidelines and incorporation of chromoendoscopy training as part of the national colonoscopy training program may improve adherence to guidelines.

Safety and efficacy of transitioning inflammatory bowel disease patients from intravenous to subcutaneous infliximab: a single-center real-world experience.

Background: A new subcutaneous (SC) formulation exists for infliximab (CT-P13 SC). The aim of this study was to assess the durability of clinical and endoscopic responses after a switch from intravenous (IV) to SC infliximab. Methods: Patients were transitioned on maintenance infliximab, including those with dose-optimized therapy. The primary outcome was clinical, biochemical and overall remission at 6 months, as defined by a Harvey-Bradshaw Index <5 for Crohn's disease or a partial Mayo score <3 for ulcerative colitis, C-reactive protein less than 10 mg/L, and fecal calprotectin less than 100 µg/g. Results: Forty patients were switched from IV to SC infliximab. Twenty-seven (68%) had a diagnosis of Crohn's disease and 13 (33%) had ulcerative colitis. Twenty-three (58%) were on 5 mg/kg of IV infliximab every 8 weeks and 15 (38%) 5 mg/kg every 6 weeks. There were 2 patients (4%) on 10 mg/kg every 6 weeks. At the time of their switch, 37 (93%) patients were in clinical remission, 25 (76%) were in biochemical remission, and 25 (76%) were in both biochemical and clinical remission. At 6 months the proportion of patients in clinical remission decreased from 93% to 82%, with an overall relapse rate of 11%. Treatment persistence at 6 months was 77.5%. Conclusion: Switching patients from IV infliximab to 120 mg fortnightly SC injections is a safe and effective option for the treatment of inflammatory bowel disease, including for those patients on dose-escalated infliximab or with active disease at the time of switch.

Combination therapy is not associated with improved rates of clinical or endoscopic remission in patients with inflammatory bowel disease treated with ustekinumab or vedolizumab: a retrospective study.

Background: Management of inflammatory bowel disease (IBD) involves biological agents, often in combination with thiopurines or methotrexate. The aim of our study was to compare clinical and endoscopic outcomes in IBD patients treated with vedolizumab or ustekinumab, as monotherapy or in combination with thiopurines or methotrexate. Methods: We conducted a retrospective cohort study of all patients aged ≥18 years with a diagnosis of ulcerative colitis or Crohn's disease, commenced on vedolizumab or ustekinumab between October 2015 and March 2022. Primary outcome was clinical remission or response calculated by partial Mayo score (remission: <3; response: improvement >1) for ulcerative colitis or Harvey-Bradshaw index (<5, >2 respectively) for Crohn's disease over 1 year. Secondary endpoints were treatment failure, relapse, endoscopic remission at 1 year. Statistical analysis was done using 2-sample Student's t and chi-square tests. Results: A total of 159 IBD patients were included in the study, 85 (53%) on vedolizumab and 74 (47%) on ustekinumab. For those on vedolizumab, 61 (72%) patients had ulcerative colitis, and 24 (28%) has Crohn's disease. All patients on ustekinumab had Crohn's disease. Mean disease duration in was 9.4 and 13.5 years respectively. There was no difference in clinical response or remission for vedolizumab or ustekinumab monotherapy compared to combination therapy at 1 year. There was also no difference in treatment failure, relapse or endoscopic remission. Conclusion: Combining vedolizumab or ustekinumab with an immunomodulator is not superior to monotherapy in terms of clinical response or endoscopic remission up to 1 year in IBD.

Peripheral parenteral nutrition: An evaluation of its use, safety and cost implications in a tertiary hospital setting.

BACKGROUND AND AIMS: Malnutrition is a common challenge among hospitalised patients and its associatiation with poor patient health-related outcomes places a significant financial burden on the healthcare system. Total parenteral nutrition (TPN) is the primary means for providing nutrition to individuals in whom enteral feeding is not possible but is costly and requires invasive central venous access. Peripheral parenteral nutrition (PPN) provides a suitable option for early nutrition provision in select patients; however, its routine use has been limited by safety and tolerability concerns, with high rates of phlebitis reported in previous studies. The objectives of this study were to review the use, safety, and costs of PPN in an Australian tertiary hospital. METHODS: A single-site, prospective observational study was conducted over 15 months in a tertiary hospital. 139 participants (87 male and 52 female) were enrolled in the study. Data collected assessed the indication for PPN initiation, compliance with the hospital's protocols for PPN, total fasting days, the proportion of the patient's total energy and protein requirements provided by PPN, the incidence of phlebitis and potential cost implications associated with the use of PPN. RESULTS: 139 patients (62.6% male), median age 62 years (IQR (interquartile range) 48-74) were enrolled. Most patients had an emergency admission (80.6%) under a general surgical team (84.2%). Forty-eight patients (34.5%) were malnourished, as assessed by the Subjective Global Assessment tool (SGA). Patients fasted for a median of 3 days (IQR 2-5) before PPN commencement, with a median duration of PPN use of 3 days (IQR 2-4). PPN provided an average of 61.6% of the patients' required caloric intake and 46.4% of protein requirements. Progression to TPN was observed in 34.5% of patients. There were low rates of complications with phlebitis observed in 3.7%, extravasation in 1.1%, and no patients developed septicaemia, despite suboptimal compliance with the recommended cannula management guidelines for PPN (66.4% compliant). The cost of PPN was estimated to be AUD$187 per patient day. CONCLUSION: PPN is an effective short-term nutrient delivery solution to facilitate early feeding with small numbers of patients requiring transition to TPN. PPN was safe with low rates of cannula complications. Costs were favourable, with potentially significant cost savings as compared with TPN.

Prevalence of gastrointestinal malignancy in non-anemic iron deficiency and significance for endoscopic screening: A Western Australian multicenter cohort study.

BACKGROUND AND AIM: There is a paucity of evidence regarding non-anemic iron deficiency as a predictor for colorectal cancer and therefore the indication for endoscopic evaluation. This study explores the rates of malignancy in adults with iron deficiency with and without anemia. METHODS: A retrospective multicenter diagnostic cohort study was conducted across two Australian health services. All cases that underwent both esophagogastroduodenoscopy and colonoscopy between September 1, 2018, and December 31, 2019, for the investigation of iron deficiency were included, and the cohort was divided into anemic and non-anemic arms. Multivariate binomial logistic regression was performed to establish clinical characteristics associated with neoplasia. RESULTS: Five hundred eighty-four patients underwent endoscopic evaluation over a 16-month period. There was a significantly higher rate of malignancy in the iron deficiency anemia arm as compared with those without anemia (8.76% vs 1.20%, P < 0.01). Gastrointestinal pathology to account for iron deficiency was identified in > 60% of the total cohort. The presence of anemia (odds ratio [OR] 6.87, P < 0.01) and male gender (OR 3.01, P = 0.01) were significant predictors of malignancy. CONCLUSION: This study demonstrates that anemic iron deficiency confers a significantly greater risk of gastrointestinal cancer compared with non-anemic iron deficiency. Additionally, over 60% of patients had gastrointestinal pathology to account for iron deficiency overall, supporting the need to perform baseline endoscopy in patients with iron deficiency.

Switching Australian patients with moderate to severe inflammatory bowel disease from originator to biosimilar infliximab: a multicentre, parallel cohort study.

OBJECTIVE: To examine whether non-medical switching of patients with inflammatory bowel disease (IBD) from originator infliximab to a biosimilar (CT-P13, Inflectra) is safe and clinically non-inferior to continued treatment with originator infliximab. DESIGN: Prospective, open label, multicentre, parallel cohort, non-inferiority study in seven Australian hospitals over 48 weeks, May 2017 - October 2019. PARTICIPANTS: Adults (18 years or older) with IBD receiving maintenance originator infliximab (Remicade) who had been in steroid-free clinical remission for at least 12 weeks. INTERVENTION: Managed program for switching patients in four hospitals from originator to biosimilar infliximab (CT-P13); patients in three other hospitals continued to receive originator infliximab (control). MAIN OUTCOME MEASURES: Clinical disease worsening requiring infliximab dose escalation or change in therapy. RESULTS: The switch group included 204 patients, the control group 141 patients with IBD. Ten patients in the control group (7%) and 16 patients switched to CT-P13 (8%) experienced clinical deterioration; the adjusted risk difference (control v switch group) was -1.1 percentage points (95% CI, -6.1 to 8.2 percentage points), within our pre-specified non-inferiority margin of 15 percentage points. Serious adverse events leading to infliximab discontinuation were infrequent in both the switch (six, 3%) and control (six, 4%) groups. CONCLUSION: Switching patients with IBD from originator to biosimilar infliximab is safe and non-inferior to continuing treatment with originator infliximab. Moreover, the introduction of biosimilar infliximab, by increasing market competition, has resulted in substantial cost savings for the Pharmaceutical Benefits Scheme.

Ileocolonic End-to-End Anastomoses in Crohn's Disease Increase the Risk of Early Post-operative Endoscopic Recurrence in Those Undergoing an Emergency Resection.

BACKGROUND AND AIM: Several risk factors affecting post-operative recurrence in Crohn's disease patients have been studied, and of these, the role of the anastomosis remains contentious. We aimed to compare the risk of developing early post-operative endoscopic recurrence (EPER), in resections that had an end-to-end anastomosis (ETEA) to a side-to-side anastomosis (STSA). METHODS: All Crohn's disease patients that underwent an ileocolic or small bowel resection between January 2012 and June 2017 at two tertiary IBD centres were reviewed retrospectively. Included patients had a minimum of 12-month clinical follow-up and a colonoscopy within 12 months of the resection or stoma reversal. Univariate and multivariate binary logistic regression analyses determined the independent risk factors for early post-operative endoscopic recurrence, defined as a Rutgeerts score of ≥ i2b. RESULTS: Ninety-two resections associated with an ETEA or a STSA were included for analysis. The ETEA was the most common anastomosis, constructed in 55 patients (59.8%). Forty-nine operations (53.3%) resulted in a ≥ i2b recurrence at the first surveillance colonoscopy. The multivariate analysis showed that there was no difference between the ETEA and STSA in determining the odds ratio (OR) for developing EPER (OR = 2.41 (0.95-6.05), P = 0.06). In those that underwent a resection emergently however, the significant determinants of EPER were as follows: having an ETEA (OR = 38.12 (2.44-595.87), P = 0.01), failing to commence a biologic and/or an immunosuppressant early (OR = 24.21 (1.69, 347.81), P = 0.02), and active smoking (OR = 7.19 (1.12-46.21), P = 0.04). CONCLUSION: The ETEA is best avoided in those undergoing an emergency resection. The early commencement of a biologic and/or an immunosuppressant and smoking cessation is imperative this high-risk group of patients.

Infliximab-induced optic neuritis.

Antitumour necrosis factor alpha agents are important treatments in many inflammatory conditions including rheumatoid arthritis, psoriatic arthritis and the inflammatory bowel diseases. However, there have been case reports of optic neuritis and other demyelinating diseases as complications of these agents. This case report presents a patient with ulcerative colitis on infliximab who presented with sudden onset mono-ocular visual field loss and highlights the diagnosis and management of infliximab-induced optic neuritis.

Physiological and psychological stress in pregnant women with quiescent inflammatory bowel disease: A pilot study using salivary biomarkers.

BACKGROUND: Pregnant women with inflammatory bowel disease (IBD) are more likely than the general pregnant population to experience adverse maternofetal outcomes, especially if the disease is active at the time of conception and during pregnancy. Elevated stress is often seen in patients with chronic diseases and could account for these outcomes. Salivary cortisol and alpha-amylase (sAA) are novel biomarkers of stress, reflecting the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, respectively. Our aim in this pilot study was to assess stress differences between pregnant women with inactive IBD and matched controls using psychometric questionnaires and salivary biomarker measures. METHODS: Thirteen pregnant women with quiescent IBD (6 Crohn's disease, 7 ulcerative colitis) were matched (1:3) to 39 expectant mothers without IBD by parity and gestational age. Participants completed several psychometric questionnaires assessing stress, and salivary cortisol and sAA were collected as objective biomarkers of stress during pregnancy. RESULTS: Pregnant women with quiescent IBD did not demonstrate significant differences on any psychometric measures of stress or salivary biomarker measures when compared with controls (all P > 0.05). Pregnant women with quiescent IBD demonstrated similar cortisol and sAA awakening responses (both P > 0.05) and total levels of cortisol and sAA production (both P > 0.05) when compared with controls. CONCLUSIONS: Pregnant women with well-controlled IBD do not experience demonstrable differences in psychological stress or dysregulation of salivary stress biomarkers when compared with non-IBD controls. The effect of chronic disease may be evaluated in future studies by including a comparative group of pregnant women with active IBD.

Anti-TNF-induced lupus in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Anti-Tumor Necrosis Factor (TNF)-induced lupus (ATIL) is a distinct clinical entity, increasingly recognized in patients with inflammatory bowel disease treated with anti-TNF therapy. Our aims were to evaluate the incidence and clinical and serological markers of ATIL in this population. METHODS: This observational cohort study reviewed 454 patient treatment courses with anti-TNF therapy (300 infliximab and 154 adalimumab). A diagnosis of ATIL was based on the most widely accepted diagnostic criteria: (i) a temporal relationship between symptoms and anti-TNF therapy and resolution of symptoms following cessation of the offending medication; (ii) at least one serologic American College of Rheumatology (ACR) criterion of Systemic Lupus Erythematosus (SLE); and (iii) at least one nonserological criterion such as arthritis, serositis, or rash. Clinical, demographic, and serological predictors were evaluated. RESULTS: The incidence rate of ATIL was 5.7% for infliximab and 0.6% for adalimumab, which are much higher than previously reported postmarketing estimates. The median duration to diagnosis following commencement of anti-TNF therapy was 15 months (3-62 months). ATIL occurs more commonly patients that commence therapy at an older age (46.47 years ± 13.79 years vs. 38.85 years ± 14.75 years, P = 0.033). CONCLUSIONS: ATIL is a significant complication of anti-TNF therapy, affecting 1 in every 20 patients who commence infliximab. A panel of serological markers is useful to confirm the diagnosis and exclude other conditions that may mimic ATIL. Clinicians using anti-TNF medications should counsel patients about this potential risk and monitor for clinical manifestations of lupus during routine follow up.

Complementary and alternative medications in the management of inflammatory bowel disease.

The use of complementary and alternative medications (CAM), products, and therapies not considered to be part of conventional medicine is common among patients with inflammatory bowel disease (IBD). Patients often turn to these therapies as they are considered natural and safe, with significant benefit reported beyond disease control. There is emerging evidence that some of these therapies may have anti-inflammatory activity; however, robust evidence for their efficacy in modulating disease activity is currently lacking. Patients often avoid discussing the use of CAM with their physicians, which may lead to drug interactions and/or reduced adherence with conventional therapy. It is important for physicians to be aware of the commonly used CAM and current evidence behind these therapies in order to better counsel their patients about their use in the management of IBD. This narrative review provides an overview of the evidence of the more commonly used CAM in patients with IBD.

The impact of pregnancy on biologic therapies for the treatment of inflammatory bowel disease.

Active inflammatory bowel disease during conception and pregnancy has been associated with adverse materno-fetal outcomes. Patients are often unduly concerned about the adverse effects of biologic medications on the growing fetus, however, continuing therapy is advised, with potential risks of therapy outweighed by the risks of active maternal disease. A number of physiological changes associated with pregnancy can alter the absorption, distribution and elimination of these therapies, which may impact on their safety and efficacy. We review the current evidence regarding the effects of pregnancy on the pharmacokinetics of biologic therapies, as well as drug concentration measurements during pregnancy and at time of delivery. A greater understanding of the impact of pregnancy on the pharmacokinetics of biologic therapies and the emerging utilisation of drug concentration monitoring during pregnancy may lead to improved materno-fetal outcomes in patients with inflammatory bowel disease.

Anti-MADCAM therapy for ulcerative colitis.

Introduction: The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) plays a key role in the endothelial adhesion and migration of lymphocytes to sites of inflammation in inflammatory bowel disease. Therapies that target this pathway appear to be a promising therapeutic approach in the management of ulcerative colitis (UC).Areas covered: This review provides a summary of the preclinical and available clinical data on the safety and efficacy of ontamalimab (SHP647), a fully human monoclonal antibody that binds and inhibits the action of MAdCAM-1.Expert opinion: Intestinal immune cell trafficking is emerging as an important component in the pathogenesis of UC. Ontamalimab (SHP647) inhibits this process by preventing the binding of integrins found on the surface of lymphocytes and the endothelial ligand adhesion molecule MAdCAM-1. This monoclonal antibody has already demonstrated safety and efficacy in phase II clinical trials. Its targeted mechanism of action suggests a superior safety profile as compared with the current systemic immunosuppressive therapies. Results from the phase III trials are awaited to establish ontamalimab (SHP647) as a therapeutic option in the management of UC.

Management of Inflammatory Bowel Diseases in Special Populations: Obese, Old, or Obstetric.

The epidemiology of inflammatory bowel disease (IBD) is progressively evolving impacting the type of patients with IBD we will see in clinical practice. In this review, we discuss specific challenges and solutions in the management of (1) obese, (2) older and (3) obstetric (pregnant) patients with IBD. With the global obesity epidemic, almost 1 in 3 patients with IBD are obese. Obesity is associated with greater difficulty in achieving remission, higher risk of disease relapse and higher burden and costs of hospitalization in patients with IBD. Obese patients also have inferior response to biologic therapy related to altered pharmacokinetics and obesity-mediated chronic inflammation. Surgical management of obese patients with IBD is also challenging. Similar to obesity, the prevalence of IBD in older patients is rising and it is anticipated that almost one-third of patients with IBD will be older than 60 years within the next decade. Older patients present unique diagnostic and therapeutic dilemmas, and management of these individuals warrants careful consideration of the risks of disease-related versus treatment-related complications, non-IBD-related extra-intestinal complications (eg, cardiovascular disease, malignancy), in the context of individual values, preferences, functional status and comorbidities. With evolving therapeutics, medical management of IBD surrounding pregnancy continues to be challenging. Overall, the management of pregnant patients requires a pro-active, multidisciplinary approach, with an emphasis on optimal disease control not just during, but prior to pregnancy. This often involves continuation of highly effective therapies, of which the vast majority are safe during pregnancy and breastfeeding, resulting in a reduction of risk of adverse maternal fetal outcomes.

Insights into the role of cannabis in the management of inflammatory bowel disease.

Over the last decade, interest in the therapeutic potential of cannabis and its constituents (e.g. cannabidiol) in the management of inflammatory bowel diseases (IBD) has escalated. Cannabis has been increasingly approved for a variety of medical conditions in several jurisdictions around the world. In animal models, cannabinoids have been shown to improve intestinal inflammation in experimental models of IBD through their interaction with the endocannabinoid system. However, the few randomized controlled trials of cannabis or cannabidiol in patients with IBD have not demonstrated efficacy in modulating inflammatory disease activity. Cannabis may be effective in the symptomatic management of IBD. Given the increasing utilization and cultural acceptance of cannabis, physicians need to be aware of its safety and efficacy in order to better counsel patients. The aim of this review is to provide an overview of the role of cannabis in the management of patients with IBD.

A Pharmacological Approach to Managing Inflammatory Bowel Disease During Conception, Pregnancy and Breastfeeding: Biologic and Oral Small Molecule Therapy.

The inflammatory bowel diseases commonly affect individuals during their peak reproductive years. Patients are often concerned about the impact of medical therapies on their ability to conceive, effect on the fetus, as well as the ability to breastfeed, which has led to poor medical adherence during pregnancy. However, most medications are safe, and discontinuation may lead to active disease, which is associated with adverse materno-fetal outcomes. The anti-TNF biologic therapies, infliximab and adalimumab have been extensively studied in the context of pregnancy. They are actively transferred to the placenta during the second and third trimesters; these have not been associated with an increased rate of congenital abnormalities or fetal death. The minimal amounts of drug that are transferred to breast milk are proteolyzed by the infant's digestive system with no reported short- or long-term adverse effects. There is a paucity of clinical data for the other approved anti-TNF agents or newer anti-integrin (vedolizumab) and anti-interleukin (ustekinumab) therapies used in the management of inflammatory bowel disease; however, no significant safety signals have been documented thus far. The new oral small molecule therapy, tofacitinib is teratogenic in animal models and is contra-indicated in patients attempting pregnancy. It is important that patients, as well as physicians managing patients with these conditions, be aware of the impact of these medical therapies during pregnancy.

Anemia in hospitalized patients: an overlooked risk in medical care.

BACKGROUND: This study investigated the association between nadir anemia and mortality and length of stay (LOS) in a general population of hospitalized patients. STUDY DESIGN AND METHODS: A retrospective cohort study of tertiary hospital admissions in Western Australia between July 2010 and June 2015. Outcome measures were in-hospital mortality and LOS. RESULTS: Of 80,765 inpatients, 45,675 (56.55%) had anemia during admission. Mild and moderate/severe anemia were independently associated with increased in-hospital mortality (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.36-1.86, p = 0.001; OR 2.77, 95% CI 2.32-3.30, p < 0.001, respectively). Anemia was also associated with increased LOS, demonstrating a larger effect in emergency (mild anemia-incident rate ratio [IRR] 1.52, 95% CI 1.48-1.56, p < 0.001; moderate/severe anemia-IRR 2.18, 95% CI 2.11-2.26, p < 0.001) compared to elective admissions (mild anemia-IRR 1.30, 95% CI 1.21-1.41, p < 0.001; moderate/severe anemia-IRR 1.69, 95% CI 1.55-1.83, p < 0.001). LOS was longer in patients who developed anemia during admission compared to those who had anemia on admission (IRR 1.13, 95% CI 1.10-1.17, p < 0.001). Red cell transfusion was independently associated with 2.23 times higher odds of in-hospital mortality (95% CI 1.89-2.64, p < 0.001) and 1.31 times longer LOS (95% CI 1.25-1.37, p < 0.001). CONCLUSION: More than one-third of patients not anemic on admission developed anemia during admission. Even mild anemia is independently associated with increased mortality and LOS; however, transfusion to treat anemia is an independent and additive risk factor.

Vedolizumab-induced acute pancreatitis: the first reported clinical case.

Drug-induced acute pancreatitis (DIAP) is a rare, but clinically significant diagnosis. Vedolizumab, an α4ß7 integrin inhibitor, which was approved in 2015 for treatment of moderate to severe inflammatory bowel disease, is a well-tolerated medication with a favourable safety profile and minimal serious adverse events in premarketing clinical trials. We present the first reported case of acute pancreatitis directly attributable to vedolizumab.