Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding.

OBJECTIVE: Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD. DESIGN: A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported. RESULTS: Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary. CONCLUSION: These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.

Selective internal radiation therapy for hepatocellular carcinoma: A 15-year multicenter Australian cohort study.

BACKGROUND AND AIM: The exact place for selective internal radiation therapy (SIRT) in the therapeutic algorithm for hepatocellular carcinoma (HCC) is debated. There are limited data on its indications, efficacy, and safety in Australia. METHODS: We performed a multicenter retrospective cohort study of patients undergoing SIRT for HCC in all Sydney hospitals between 2005 and 2019. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events. RESULTS: During the study period, 156 patients underwent SIRT across 10 institutions (mean age 67 years, 81% male). SIRT use progressively increased from 2005 (n = 2), peaking in 2017 (n = 42) before declining (2019: n = 21). Barcelona Clinic Liver Cancer stages at treatment were A (13%), B (33%), C (52%), and D (2%). Forty-four (28%) patients had tumor thrombus. After a median follow-up of 13.9 months, there were 117 deaths. Median overall survival was 15 months (95% confidence interval 11-19). Independent predictors of mortality on multivariable analysis were extent of liver involvement, Barcelona Clinic Liver Cancer stage, baseline ascites, alpha fetoprotein, and model for end-stage liver disease score. Median progression-free survival was 6.0 months (95% confidence interval 5.1-6.9 months). Following SIRT, 11% of patients were downstaged to curative therapy. SIRT-related complications occurred in 17%: radioembolization-induced liver disease (11%), pneumonitis (3%), gastrointestinal ulceration, and cholecystitis (1% each). Baseline ascites predicted for radioembolization-induced liver disease. CONCLUSION: We present the largest Australian SIRT cohort for HCC. We have identified several factors associated with a poor outcome following SIRT. Patients with early-stage disease had the best survival with some being downstaged to curative therapy.

Assisted Reproductive Technology in Crohn's Disease and Ulcerative Colitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Infertility may occur in women with Crohn's disease (CD) and ulcerative colitis (UC), especially after surgery such as ileal pouch-anal anastomosis (IPAA). Assisted reproductive technology (ART) may be an option, but the safety and efficacy in this setting has been based on small cohorts to date. We performed a systematic review and meta-analysis to address this data gap. METHODS: A systematic review and random-effects meta-analysis was performed until May 2020. The primary outcomes were pregnancy and live birth rates per cycle of ART. RESULTS: Eleven studies met inclusion criteria for the systematic review and 4 for the meta-analysis. Compared with the general population, women with CD (with and without previous surgery) had no difference in pregnancy rates (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.45-1.05) but had reduced live births (OR = 0.67, 95% CI: 0.53-0.85) per cycle of ART. ART live birth rates are not reduced in women with medically managed CD; however, they are 49%-71% lower after CD-related surgery. Women with UC had no difference in both pregnancy rates (OR = 0.99, 95% CI: 0.63-1.55) and live birth rates (OR = 0.88, 95% CI: 0.67-1.17); however, live birth rates were reduced after IPAA failure (hazard ratio = 0.36, 95% CI: 0.14-0.92). Two studies did not identify any significant safety signals. DISCUSSION: ART is safe and effective in patients with UC and medically managed CD, with pregnancy and live birth rates similar to that of the general population. However, within the limitations of the available literature, current data suggest that efficacy is reduced in women with CD-related surgery and IPAA failure. Greater gastroenterologist awareness of ART is needed to facilitate timely fertility therapy referral when indicated, particularly in CD.

Palliative care in hepatocellular carcinoma.

Hepatocellular carcinoma is a common cancer with a poor prognosis, associated with high economic costs and a significant burden of disease. While it is often asymptomatic in the early stages, patients may experience great discomfort from advanced disease, treatment adverse effects, or decompensation of underlying cirrhosis. Palliative care has the potential to markedly improve quality of life, physical, and psychological symptoms in patients with end-stage liver disease, and has been shown to prolong survival in some nonhepatocellular carcinoma malignancies. However, this service is underutilized in hepatocellular carcinoma, and referrals are frequently late due to factors such as stigmatization, inadequate resources, lack of education for nonpalliative care physicians and inadequate modeling for integration of palliative and supportive care within liver disease services. In the future, education workshops, population-based awareness campaigns, increased funding and improved models of care, may improve the uptake of palliative care and subsequently optimize patient care, particularly towards the end of life.

Frailty in advanced liver disease.

Prognostication of patients with cirrhosis is complex, depending on more than just the severity of liver disease. Scores such as the model for end-stage liver disease (MELD) and Child Pugh can assist with prognostication, yet by focusing on physiological parameters they fail to completely capture the elements contributing to a patient's clinical status. Evidence is increasing to support an important role for physical functioning in patient outcomes. Frailty has been increasingly recognised in medical literature over recent years, including in hepatology where it is identified in nearly half of cirrhosis patients. It is a complex construct consisting of multisystemic physiological decline and increased vulnerability to stressors. Diagnosis is complicated by lack of a consensus definition and measurement tool for frailty in cirrhosis. Frailty heralds a poor prognosis, predicting increased morbidity and mortality both pre- and postliver transplant, independent of MELD score. It is thought to be reversible, with promising data supporting prehabilitation and lifestyle intervention programs. In the future, assessment of patients with cirrhosis is likely to incorporate a measure of frailty, however, further research is required.

Oral and upper gastrointestinal Crohn's disease.

Crohn's disease is a heterogeneous, inflammatory condition that can affect any location of the gastrointestinal tract. Proximal gastrointestinal involvement occurs in 0.5-16% of patients, and it is usually diagnosed after recognition of intestinal disease. Symptoms are often mild and nonspecific; however, upper gastrointestinal disease predicts a more severe Crohn's phenotype with a greater frequency of complications such as obstruction and perforation. Gastroscopy and biopsy is the most sensitive diagnostic investigation. There is a paucity of data examining the treatment of this condition. Management principles are similar to those for intestinal disease, commencing with topical therapy where appropriate, progressing to systemic therapy such as glucocorticoids, 5-aminosalicylic acid, immunomodulators, and biologics. Acid suppression therapy has symptomatic but no anti-inflammatory benefit for gastroduodenal and esophageal involvement. Surgical intervention with bypass, strictureplasty, or less frequently, endoscopic balloon dilation may be required for complications or failed medical therapy.

First-trimester exposure to tofacitinib in ulcerative colitis: A case report of a healthy newborn and literature review.

Tofacitinib is contraindicated in pregnancy. We present a patient with ulcerative colitis on tofacitinib who had an unplanned pregnancy. Tofacitinib was ceased, switched to vedolizumab, and she gave birth to a healthy newborn at term. Case reports of reassuring outcomes provide real-world data that assists decision-making for future patients.

Reproductive Safety Issues of Novel Small Molecules for the Treatment of Inflammatory Bowel Disease: A Systematic Review.

Maintenance of remission during pregnancy is vital for women with inflammatory bowel disease (IBD). The antenatal safety of novel small molecules for IBD is yet to be ascertained. We aimed to describe the current evidence on reproductive data regarding small-molecule drugs. We performed a systematic review searching Embase Classic + Embase and Ovid MEDLINE for reproductive outcomes for tofacitinib, filgotinib, upadacitininb, and ozanimod. Additionally, we asked the manufacturers for available data on file regarding reproduction. We analysed data from 10 sources; six studies and four manufacturer reports were identified from our search. Significant malformation risks were reported for tofacitinib, filgotinib, upadacitininb, and ozanimod in animal studies. In 126 tofacitinib-exposed pregnancies, there were 55 live births with 2 congenital malformations and 1 serious infant infection, 14 terminations, 15 miscarriages, and 42 outcomes unknown. In 50 filgotinib-exposed pregnancies, there were 20 healthy babies, 1 congenital malformation, 9 terminations, 10 miscarriages, and 10 outcomes unknown. In 78 upadacitinib-exposed pregnancies, there were 30 healthy babies, 15 terminations, 15 miscarriages, and 18 outcomes unknown. In 60 ozanimod-exposed pregnancies, there were 31 live births with 1 congenital malformation, 1 case of intra-uterine growth restriction, 1 case of neonatal icterus, 13 terminations, 9 miscarriages, and 8 unknown outcomes. Animal data suggest significant risks of malformations for tofacitinib, filgotinib, upadacitininb, and ozanimod. Human data from clinical trials and real-world observations do not show concerning data so far, but these are very limited. Currently, alternative treatments should be used for IBD during pregnancy.

Managing Inflammatory Bowel Disease in Pregnancy: Health Care Professionals' Involvement, Knowledge, and Decision Making.

BACKGROUND: The management of pregnant women with inflammatory bowel disease (IBD) is complex. We aimed to assess health care professionals' (HCPs) theoretical and applied knowledge of pregnancy-related IBD issues. METHODS: A cross-sectional international survey was distributed to HCPs providing IBD care between October 2020 and March 2021. Knowledge was assessed using the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow; range, 0-17). Decision-making was assessed by free text responses to 3 clinical scenarios scored against predetermined scoring criteria (maximum score 70). RESULTS: Among 81 participants, median CCPKnow score was 16 (range, 8-17), and median total scenario score was 29 (range, 9-51). Health care professionals who treat >10 IBD patients per week (CCPKnow P = .03; scenarios P = .003) and are more regularly involved in pregnancy care (CCPKnow P = .005; scenarios P = .005) had significantly better scores. Although CCPKnow scoring was consistently high (median score ≥15) across all groups, consultants scored better than trainees and IBD nurses (P = .008 and P = .031). Median scenario scores were higher for consultants (32) and IBD nurses (33) compared with trainees (24; P = .018 and P = .022). There was a significant positive correlation between caring for greater numbers of pregnant IBD patients and higher CCPKnow (P = .001, r = .358) and scenario scores (P = .001, r = .377). There was a modest correlation between CCPKnow and scenario scores (r = .356; P < 0.001). CONCLUSIONS: Despite "good" theoretical pregnancy-related IBD knowledge as assessed by CCPKnow, applied knowledge in the scenarios was less consistent. There is need for further HCP education and clinical experience to achieve optimal standardized care for IBD in pregnancy.

Objective assessment of pregnancy-specific IBD knowledge among gastroenterology health care professionals is good; however, clinician application of knowledge in decision-making is less consistent. There is need for further clinician education to provide optimal standardized care for IBD in pregnancy.

Planning to conceive within a year is associated with better pregnancy-specific disease-related patient knowledge and better medication adherence in women of childbearing age with inflammatory bowel disease.

Background: Adherence to inflammatory bowel disease (IBD) medication is crucial to maintain remission, especially during pregnancy. Objective: To examine the influence of family planning and pregnancy-related patient knowledge regarding IBD and pregnancy on adherence. Design: Cross-sectional survey study. Methods: We surveyed female patients with IBD aged 18-35 years, who at recruitment to the UK IBD BioResource had not had children. We elicited disease and treatment history, demographics and family planning status via an online questionnaire. Patient knowledge as assessed by the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow) and adherence by visual analogue scale (VAS). Results: In 326 responders (13.8% response rate), good adherence (VAS ⩾ 80) was found in only 38.35%. Disease- and treatment-related factors were not significantly associated with good adherence, except for methotrexate (70.0% adherent of 10 exposed patients versus 37.2% non-exposed; p = 0.036). Patients planning pregnancy for the next year were more often adherent (59.0% versus 35.5%; p = 0.019) and knowledgeable (median CCPKnow 8 versus 7; p = 0.035) compared to those in other family planning categories. Pregnancy-related patient knowledge was significantly associated with adherence (Pearson correlation 0.141; p = 0.015). Adherent patients had significantly higher CCPKnow scores than non-adherent patients (median 8 versus 6; p = 0.009). On binary regression analysis, only planning to conceive within 12 months was independently associated with better adherence (p = 0.016), but not methotrexate exposure (p = 0.076) and CCPKnow (p = 0.056). Conclusions: In a cohort of women of childbearing age with IBD overall medication, adherence was low. Planning to conceive within the next year was associated with better adherence and greater patient knowledge.

Medication adherence in women with IBD of childbearing age likely associated with disease knowledge.

Background: Medication adherence in inflammatory bowel disease (IBD) is crucial, particularly during pregnancy. Unplanned pregnancies are common; therefore, efforts to maximise adherence should not be restricted to pregnant women. Objectives: We aimed to assess medication adherence in women with IBD of childbearing age, regardless of their reproduction plans. Design: We performed a multi-centre pilot questionnaire study of women with IBD age 18-45 years. Methods: Survey questions included patient demographics, disease history, and validated assessments of IBD and pregnancy knowledge, medication adherence and quality of life. The primary outcome was rates and predictors of medication adherence. Results: In all, 72 women [58.3% Crohn's disease (CD) and 37.5% ulcerative colitis] completed the survey. The median patient age was 30 years [interquartile range (IQR): 24.8-36.0) and 37.5% had children. Medication adherence was high (84%; median Medication Adherence Report Scale: 19.0/20; IQR: 17.0-20.0). Knowledge scores were adequate for both the Crohn's and Colitis Knowledge (CCKnow; median: 15.5/30; IQR: 12.3-18.0) and Crohn's and Colitis Pregnancy Knowledge (CCPKnow; median: 8.0/17; IQR: 4.0-11.0). Disease knowledge was predictive of high medication adherence (CCPKnow: p = 0.02; CCKnow: p ⩽ 0.01). Higher adherence was significantly associated with a diagnosis of CD (p = 0.01), exposure to biological agents (p = 0.03) and immunomodulators (p = 0.04), childbearing after diagnosis with IBD (p = 0.03), and correctly understanding the importance of delivery modality (p = 0.02) and IBD activity in pregnancy (p = 0.01). Conclusions: Following dedicated education at the IBD clinic, medication adherence, disease-specific and pregnancy-specific knowledge in women with IBD of childbearing age tends to be high. Unplanned pregnancies are frequent; therefore, we should aim to maximise medication adherence in all women of childbearing age to optimise maternofoetal outcomes if unexpected pregnancies occur.

Gastroenterology team members' knowledge and practices with fertility therapy for women with inflammatory bowel disease.

Introduction: Fecundity may be reduced in women with active inflammatory bowel disease (IBD) or prior IBD-related surgery, and these women may require assisted reproductive technology (ART). There are no guidelines for women with IBD to outline referral criteria for ART. Methods: We performed a prospective, multicentre, international questionnaire of gastroenterologists, gastroenterology trainees, and IBD nurses. The primary outcome was to establish clinical practices and fertility therapy referral patterns among gastroenterology team members. We hypothesised that the lack of knowledge and awareness may delay or prevent initiation of fertility consultation referrals. Discussion: Of 182 participants, most had never initiated a referral for fertility therapy (69.8%), and of respondents who do initiate referrals, 50% wait until the patient has been unsuccessfully attempting conception for 12 months. Participants were significantly more likely to initiate a fertility therapy referral if they believed ART was effective (p = 0.038), not impeded by IBD-related surgery (p = 0.053), and if they had access to a dedicated IBD-pregnancy clinic (p = 0.027). Superior pregnancy knowledge was predictive of a greater likelihood of fertility therapy referrals (p = 0.037). All participants thought they had inadequate knowledge about ART in IBD, and 96.2% expressed desire to improve their knowledge. Conclusion: Gastroenterology team members infrequently initiate referrals for fertility therapy consultation in women with IBD, increasing their risk of remaining childless. Implementation of dedicated IBD pregnancy clinics and targeted education programmes to increase awareness of ART in women with IBD might increase referral rates and reduce infertility.

Use of medications during pregnancy and breastfeeding for Crohn's disease and ulcerative colitis.

Introduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs during childbearing years, therefore management of IBD during pregnancy is a frequent occurrence. Maintenance of disease remission is crucial to optimize pregnancy outcomes, and potential maternal or fetal toxicity from medications must be balanced against the risks of untreated IBD.Areas covered: This review summarizes the literature on safety and use of medications for IBD during pregnancy and lactation.Expert opinion: 5-aminosalicylates, corticosteroids and thiopurines are safe for use during pregnancy, while methotrexate and tofacitinib should only be used with extreme caution. Anti-TNF agents (except certolizumab), vedolizumab, ustekinumab and tofacitinib readily traverse the placenta via active transport, therefore theoretically may affect fetal development. Certolizumab only undergoes passive transfer across the placenta, thus has markedly lower cord blood levels making it likely the safest biologic agent for infants. There is reasonable evidence to support the safety of anti-TNF monotherapy and combination therapy during pregnancy and lactation. Vedolizumab and ustekinumab are also thought to be safe in pregnancy and lactation, while tofacitinib is generally avoided due to teratogenic effects in animal studies.

Review of pregnancy in Crohn's disease and ulcerative colitis.

Inflammatory bowel disease (IBD) frequently affects women of childbearing age and can have implications in pregnancy. Most women with IBD have comparable fertility with women in the general population. Fertility is reduced in women with active disease or previous ileal-pouch-anal anastomosis (IPAA) surgery and is temporarily reduced in men taking sulfasalazine. Women with IBD have an increased risk of preterm delivery, low birth weight, small-for-gestational-age infants and Cesarean section (CS) delivery, however, no increased risk of congenital abnormalities. These adverse outcomes are particularly prevalent for women with active IBD compared with those with quiescent disease. Conception should occur during disease remission to optimize maternal and fetal outcomes and reduce the risk of disease exacerbations during pregnancy. Pre-conception counseling is therefore pertinent to provide patient education, medication review for risk of teratogenicity and objective disease assessment. Most medications are safe during pregnancy and breastfeeding, with the exception of methotrexate, ciclosporin, allopurinol and tofacitinib. Delivery modality should be guided by obstetric factors in most cases; however, CS is recommended for women with active perianal disease and can be considered for women with inactive perianal disease or IPAA. In conclusion, most women with IBD have uncomplicated pregnancies. Active IBD is the predominant predictor of poor outcomes and disease exacerbations; therefore, maintenance of disease remission during and before pregnancy is crucial.

Palliative medicine referrals for hepatocellular carcinoma: a national survey of gastroenterologists.

OBJECTIVES: Palliative care (PC) service involvement for hepatocellular carcinoma (HCC) patients is suboptimal and little is known about the underlying reasons for this. We aimed to study clinicians' experience and attitudes towards PC in HCC. METHODS: A nationwide survey was conducted of consultants/trainees recruited from the Gastroenterological Society of Australia membership directory. Clinician demographics, experience and attitudes towards PC use for HCC patients were collected. RESULTS: There were 160 participants. Most attended weekly multidisciplinary team meetings (MDTM, 60%) and had no formal PC training (71%). MDTM with PC attendance was reported by 12%. Rates of PC referral increased incrementally from BCLC 0/A to D patients but were not universal even in advanced (46%) or terminal (87%) stages. Most acknowledged PC patient discussions occurred too late (61%). Those with prior PC training were more likely to refer BCLC 0/A and B patients for early PC. Referral rates for outpatient PC were higher in respondents who attended MDTM with PC present across all BCLC stages. PC service was rated good/very good by 70%/81% for outpatients/inpatients. Barriers to PC referral included clinician-perceived negative patient associations with PC (83%), clinician-perceived patient/caregiver lack of acceptance (81%/77%) and insufficient time (70%). CONCLUSIONS: PC referral for HCC patients is not universal and occurs late even in late-stage disease. Prior PC training and/or PC presence at MDTM positively influences referral practices. Barriers to PC referral are not related to quality of PC services but rather to clinician-perceived patients' negative reactions to or lack of acceptance of PC.

Knowledge and Attitudes Towards Pregnancy in Females with Inflammatory Bowel Disease: An International, Multi-centre Study.

BACKGROUND AND AIMS: Poor knowledge of inflammatory bowel disease [IBD] in pregnancy underlies unwarranted voluntary childlessness [VC], and risks poorer obstetric outcomes and adverse fetal outcomes. IBD is increasing worldwide but education on IBD issues might be heterogeneous based on cultural differences and variations in models of care. METHODS: Consecutive female IBD subjects aged 18-45 years were prospectively recruited from two dedicated IBD-pregnancy clinics, two multidisciplinary IBD clinics and nine general gastroenterology clinics. Subjects completed the validated CCPKnow [score 0-17] with questions on demographics, medical history and pregnancy knowledge. The primary outcome was knowledge per clinic-type and per geographical region. RESULTS: Surveys were completed by 717 subjects from 13 hospitals across ten countries. Dedicated IBD-pregnancy clinics had the highest knowledge, followed by multidisciplinary IBD clinics then general IBD clinics (median CCPKnow 10.0 [IQR: 8.0-11.0], 8.0 [IQR: 5.0-10.5] and 4.0 [IQR:2.0-6.0]; p < 0.001). Median CCPKnow scores in Western, Asian and Middle Eastern clinics were 9.0, 5.0 and 3.0 respectively [p < 0.001]. Dedicated IBD-pregnancy clinics, IBD support organization membership, childbearing after IBD diagnosis and employment independently predicted greater knowledge. Patient perception of disease severity [r = -0.18, p < 0.01] and consideration of VC [r = -0.89, p = 0.031] negatively correlated with CCPKnow score. The overall VC rate was 15.0% [95% CI: 12.2-18.2]. VC subjects had significantly lower pregnancy-specific IBD knowledge than non-VC subjects (median CCPKnow 4.0 [IQR: 2.0-6.0] and 6.0 [IQR: 3.0-9.0] respectively; p < 0.001). Pregnancy-specific IBD knowledge and dedicated IBD-pregnancy clinic attendance were significant negative predictors of VC. CONCLUSIONS: In this large international study we identified predictors of pregnancy-specific IBD knowledge. Dedicated IBD-pregnancy clinics had the greatest IBD-related pregnancy knowledge and lowest VC rates, reflecting the benefits of pre-conception counselling.