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Background/Objectives : Data on the real-world effectiveness and safety of selective JAK inhibitors (JAKis) in ulcerative colitis (UC) and Crohn's disease (CD) are limited. Methods : We conducted a multicentre, retrospective study to assess clinical, biochemical, and endoscopic outcomes of selective JAKis in bio-experienced UC and CD. Results : A total of 246 patients (mean age: 40.5 ± 14.5 years; 131 UC and 115 CD) were included with a median follow-up of 7.5 months. Among the CD patients receiving upadacitinib ( n = 115), 76.2% achieved clinical remission (CR) at week 12. Furthermore, 59.5% of the upadacitinib-treated UC patients ( n = 100) experienced CR at week 8. Corticosteroid-free CR (CSFCR) was achieved by 76.9% of the CD patients and 80.6% of the UC patients at week 24, while 50.0% and 36.1% experienced endoscopic remission. At week 52, 66.7% of the CD and 86.2% of the UC patients achieved CSFCR, whereas 54.5% and 52.9% had endoscopic remission. In UC, the effectiveness of upadacitinib was not compromised by prior tofacitinib failure, while the upadacitinib-treated CD patients with stricturing and penetrating disease were less likely to achieve CR by the end of the induction phase ( p = 0.04). C-reactive protein ( p [CD] < 0.0001; p [UC] < 0.0001) and faecal calprotectin ( p [CD] < 0.0001; p [UC] = 0.02) decreased significantly in both patient groups as early as week 2. Among the filgotinib-treated UC patients ( n = 31), 28.6% were in CR at week 12. At week 24 and 52, 59.1% and 60% achieved CSFCR, while 0.0% and 20.0% had endoscopic remission. Both C-reactive protein ( p = 0.04) and faecal calprotectin ( p = 0.04) decreased significantly by week 12. Hyperlipidaemia (9.7-9.8%) was the most common adverse event. Conclusions : Selective JAKis are rapidly effective and safe for treating refractory, moderate-to-severe CD and UC.

Background and Aims: Active inflammatory bowel disease at conception is associated with adverse pregnancy outcomes. International guidelines address antenatal care, but contraception counselling and risk assessment are not addressed. Data on healthcare professionals' guidance for women with IBD regarding contraception are scarce. We aimed to describe contraceptive use, preferences, knowledge, and barriers among women with IBD., Methods: A 34-item questionnaire was administered to female IBD patients aged 18-45. Disease control was measured using PRO2 and IBD Control questionnaire, and contraceptive preferences were assessed by the Contraceptive Features Survey. Logistic regression explored associations between contraceptive use, attitudes, disease remission status, and other factors., Results: Of 338 women surveyed, 243 (74%) used some form of contraception. Oral birth control pills (28%) and barrier methods (18%) were most used but 20% used long-acting methods. Women with active disease were more likely to use long-acting contraception (23%) compared to those in remission (17%). Contraceptive priorities were effectiveness (78%), ease of use (75%), and minimal side effects (68%). Only 25% women had discussed reproductive issues with their IBD clinician, though 85% were comfortable to do so. Preferred sources for reproductive counselling were IBD nurses (79%), general practitioners (75%), IBD doctors (68%), and gynaecologists (49%)., Conclusion: A quarter of women with IBD were not using any contraception, and long-acting contraceptive use was low. Women prefer effective, easy-to-use contraceptives with minimal side effects but lack knowledge on effective contraception-related issues. Better education and proactive discussions between healthcare providers and patients could improve reproductive health in women with IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Many women of childbearing age with inflammatory bowel disease (IBD) require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules tofacitinib, filgotinib, upadacitinib and ozanimod (TFUO) have shown concerning teratogenic effects, and decreased fertility in animal studies. Therefore, their use in women of childbearing age needs careful consideration., Design: RAND/University of California Los Angeles (UCLA) Appropriateness Method (RAM)., Objective: To evaluate the appropriateness of TFUO in women of childbearing age., Methods: We convened a panel of six gastroenterologists, two IBD nurses, one IBD pharmacist and three expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds., Results: All 13 statements were deemed appropriate. The panel concluded that women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception and be counselled regarding the risk in unplanned pregnancies. For women using contraception while on Janus kinase inhibitor (JAKi) therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception. TFUO are contraindicated during pregnancy and breast feeding. We recommend that women receiving TFUO cease therapy in time to establish clinical remission for at least 3 months prior to conception. Therapies other than TFUO should be considered as first-line therapy in women with IBD of childbearing age, except in select individual circumstances. TFUO may be appropriate for women of childbearing age after failure of, intolerance or contraindications to one biological agent., Conclusion: TFUO should be avoided during pregnancy and breastfeeding, and alternative therapies should be considered as first-line treatments., Summary: We provide clinical practice recommendations regarding the use of TFUO for IBD in women of childbearing age., Competing Interests: C.P.S. has received unrestricted research grants from Warner Chilcott, Janssen, Galapagos and AbbVie, has provided consultancy to Warner Chilcott, Dr Falk, AbbVie, Takeda, Fresenius Kabi, Eli Lilly, Galapagos, Ferring, Arena and Janssen, and had speaker arrangements with Warner Chilcott, Dr Falk, Galapagos, AbbVie, MSD, Pfizer, Eli Lilly, BMS, UCB, Fresenius Kabi, Celltrion and Takeda. A.K. has provided consultancy to AbbVie, Galapagos, Ferring, Warner Chilcott and Janssen and had speakers fees from AbbVie, Galapagos, Janssen, Takeda and Falk. K.K. has provided consultancy to AbbVie and Galapagos, and had speaker arrangements with AbbVie, Galapagos, Janssen and Ferring. J.L. has provided consultancy to AbbVie, Arena, BioHit, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, Pfizer and Takeda; has received speaker fees from to AbbVie, BioHit, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Janssen, MSD, Pfizer, Takeda; and research grants from Galapagos and Takeda. A.F. has provided consultancy to Warner Chilcott, Dr Falk, AbbVie, Takeda, Allergan, Galapagos, Ferring, Pharmacosmos, UCB, Bristol Myers Sqibb and Janssen, and had speaker arrangements with Warner Chilcott, Allergan, Dr Falk, Galapagos, AbbVie, Pfizer, Ferring, Pharmacosmos, Bristol Myers Squibb, Fresenius Kabi, Celltrion and Takeda. F.R. has provided consultancy to Bristol Myers Squibb, Celltrion and Takeda and had speaker arrangements with Dr Falk, Ferring, Gilead, Intercept and Pfizer. The other authors have no conflict of interests to disclose., (© The Author(s), 2024.)

Objectives: Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short, intermediate, and long-term post-discharge complications among these patients., Methods: A retrospective multicenter cohort study assessing outcomes of elderly individuals (≥60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-months post-discharge IBD-related complication rates defined as: steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6-months and mortality at 12-months among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression., Results: In a cohort of 654 patients hospitalized for IBD (age 68.9 [interquartile range {IQR}]:63.9-75.2) years, 60.9% ulcerative colitis), 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6-months, and 12-months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs. 33.1%, p=0.8; 40.5% vs. 42.5%, p=0.66; and 4.6% vs. 8%, p=0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3-months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An ulcerative colitis diagnosis was the sole risk factor for complication at 6-months (aOR 1.5). CDI did not significantly impact outcomes or interact with IBD type., Conclusions: In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1-year., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening medical emergency that occurs in up to 25% of patients with ulcerative colitis. Although intravenous corticosteroids remain the cornerstone of therapy, 30-40% of patients will not respond and need timely consideration of rescue therapy with (currently) either infliximab or ciclosporin or indeed colectomy, underscoring the importance of multidisciplinary care to ensure favourable outcomes for patients. We discuss the current evidence and present an approach to the management of ASUC for general and specialist clinicians caring for patients with ASUC., Sources of Data: The information in this review is derived from data published in peer- reviewed academic journals and registered clinical trials., Areas of Agreement: Management of acute severe colitis requires a multidisciplinary approach with early initiation with steroids and timely escalation of treatment to either medical rescue therapy or surgery., Areas of Controversy: Balancing the risks of delayed surgery vs. optimizing medical therapy, including accelerated dosing schedules for biologics, remains ambiguous., Growing Points: The position on newer molecules like Janus Kinase inhibitors, such as tofacitinib, is a growing area with early real-world data showing promise for steroid refractory ASUC., Areas Timely for Developing Research: Developing predictive biomarkers and clinical risk scores for personalized rescue therapy selection is an evolving area of research., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Optimal management of inflammatory bowel disease (IBD) in pregnancy is associated with better pregnancy outcomes. We describe management of IBD during pregnancy and maternal and fetal outcomes of patients from a tertiary UK IBD centre., Methods: This is a retrospective observational cohort study of all pregnancies occurring between 2015 and 2021 in a large tertiary IBD centre in the UK. IBD activity and management prior to, during and after pregnancy were recorded along with pregnancy and neonatal outcomes. Associations between IBD-focused interventions and any adverse pregnancy outcomes, as well as the association between IBD severity and treatments and adverse maternofetal outcomes were assessed., Results: Pregnancies in 130 women with IBD were included for analysis. The mean maternal age at delivery was 30.5 (± 4.7) years. At conception, 73 women (56.2%) were in clinical remission and 24 (18.4%) were treated with a biologic agent. Active disease during pregnancy, measured by physician global assessment, was less frequent in women who were in clinical remission at conception, compared to those not in remission at conception (16/73 21.9% vs. 39/49 79.6%; data insufficient for eight women). Active IBD at conception was associated with pre-term birth (p = 0.04). Maternal corticosteroid use in any trimester was associated with low birth weight (T1 p = 0.02; T2 p = 0.005; T3 p = 0.007). Active disease (p = 0.008) and steroid use in the third trimester (p = 0.05) were both associated with neonatal infections up to six months after birth., Conclusion: Women in clinical remission at the time of conception have favorable outcomes, consistent with prospective observational studies. Our observations emphasize the importance of high quality IBD care for women pre and post-partum in line with international recommendations., (© 2024. The Author(s).)

Background: Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly., Methods: The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence., Results: Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months., Conclusions: We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients., (© Crown copyright 2024.)

Ulcerative colitis (UC) is a chronic, relapsing-and-remitting, potentially progressive form of inflammatory bowel disease (IBD) with multidimensional and often negative effects on patients' lives. Fecal urgency, the sudden and compelling desire to defecate, often accompanied by impaired bowel control leading to frequent and urgent trips to the bathroom, is a distressing symptom, experienced by more than 50% of patients with UC. 1 Physicians frequently underestimate the burden of fecal urgency on patients' lives, with ramifications ranging from disruption in daily activities, social interactions, and emotional distress with resultant impairment in quality of life (QoL). 2,3 ., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: This study compares the effectiveness of different biologic therapies and sequences in patients with inflammatory bowel disease [IBD] using real-world data from a large cohort with long exposure., Methods: Demographic, disease, treatment, and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups., Results: In total, 13 222 evaluable patients received at least one biologic. In ulcerative colitis [UC] first-line vedolizumab [VDZ] demonstrated superior effectiveness over 5 years compared to anti-tumour necrosis factor [anti-TNF] agents [p = 0.006]. VDZ was superior to both infliximab [IFX] and adalimumab [ADA] after ADA and IFX failure respectively [p < 0.001 and p < 0.001]. Anti-TNF therapy showed similar effectiveness when used as first-line treatment, or after failure of VDZ. In Crohn's disease [CD] we found significant differences between first-line treatments over 10 years [p = 0.045], with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first-line anti-TNF failure in CD [p = 0.035]. Patients with UC or CD experiencing TNF failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF., Conclusions: We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

The peak incidence of inflammatory bowel disease (IBD) coincides with a woman's prime reproductive years. The management of IBD during pregnancy can be challenging for healthcare professionals, underpinning the need for a multi-disciplinary approach with shared decision-making with the patient. Pre-conception counselling can address patient concerns, improve pregnancy specific IBD patient knowledge and provide a personalized risk assessment, to ensure optimal maternal and fetal outcomes. Most women with IBD have fertility rates comparable with the general population, although voluntary childlessness is common among women with IBD. IBD disease activity at conception and during pregnancy is a key determinant of the course of IBD during pregnancy. Active IBD during pregnancy is associated with adverse pregnancy-related outcomes, including spontaneous abortion, small for gestational age baby and preterm birth, emphasizing the importance of ensuring disease remission prior to conception. Most IBD medications (5-aminosalicylates, thiopurines if already initiated pre-conception, corticosteroids and biologic medications) are considered safe and low risk during pregnancy and breastfeeding, except for methotrexate, JAK-inhibitors, ozanimod and allopurinol and maintaining remission throughout gestation should be the priority. Most women with IBD can have a vaginal delivery, but cesarean section should be considered in active perianal disease and history of ileal pouch surgery. This narrative review outlines the current evidence for the management of IBD in pregnancy, as well as considering the pre-conceptual and post-partum period., (© 2024. The Author(s).)

Background: A growing body of evidence underscores the beneficial impact of therapeutic drug monitoring (TDM) on the efficacy and cost-effectiveness of anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD)., Objectives: We surveyed clinician attitudes, perceptions and barriers related to TDM in IBD in the Middle East., Design: A 15-question survey was distributed through national gastroenterological societies in five Middle Eastern countries (UAE, Saudi Arabia, Kuwait, Lebanon and Egypt)., Methods: Data on clinician characteristics, demographics, utilization patterns and obstacles related to the adoption of TDM with anti-TNFs were gathered. Logistic regression analysis was used to predict factors influencing the utilization of TDM., Results: Among 211 respondents (82% male), 82% were consultants, 8% were physicians with an interest in gastroenterology (GI), and 6% were GI trainees. Of these, 152 met inclusion criteria, treating >5 IBD patients per month and ⩾1 with an anti-TNF per month. TDM was used in clinical practice by 78% (95% CI: 71-85) of respondents. TDM was utilized following the loss of response (LOR) in 93%, for primary non-response (PNR) in 40% and before restarting anti-TNF therapy after a drug holiday in 33% of respondents, while 34% used TDM proactively. No specific factors were associated with the use of TDM. Barriers to TDM use included cost (85%), time lag to results (71%) and lack of insurance reimbursement (65%). Overall knowledge of TDM (70%), interpretation and actioning of results (76%) or awareness of clinical guidelines (57%) were not perceived as barriers. If barriers were removed, 95% would use TDM more frequently; 93% for LOR, 60% for PNR, 50% when restarting after a drug holiday, and 54% would use TDM proactively., Conclusion: Most gastroenterologists use TDM for LOR, with cost, time lag and insurance reimbursement being significant barriers. Addressing these barriers would increase the judicious use of reactive and proactive TDM to optimize anti-TNF therapy in IBD., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background and Aims: Technological advances have provided innovative, adaptive, and responsive models of care for inflammatory bowel diseases [IBD]. We conducted a systematic review to compare e-health interventions with standard care in management of IBD., Methods: We searched electronic databases for randomised, controlled trials [RCT] comparing e-health interventions with standard care for patients with IBD. Effect measures were standardised mean difference [SMD], odds ratio [OR], or rate ratio [RR], calculated using the inverse variance or Mantel-Haenszel statistical method and random-effects models. Version 2 of the Cochrane tool was used to assess the risk of bias. The certainty of evidence was appraised with the GRADE framework., Results: Fourteen RCTs [n = 3111; 1754 e-health and 1357 controls] were identified. The difference in disease activity scores (SMD 0.09, 95% confidence interval [CI]: -0.09-0.28) and clinical remission (odds ratio [OR] 1.12, 95% CI: 0.78-1.61) between e-health interventions and standard care were not statistically significant. Higher quality of life [QoL] [SMD 0.20, 95% CI: 0.05-0.35) and IBD knowledge [SMD 0.23, 95% CI: 0.10-0.36] scores were noted in the e-health group, and self-efficacy levels [SMD -0.09, 95% CI: -0.22-0.05] were comparable. E-health patients had fewer office [RR 0.85, 95% CI: 0.78-0.93] and emergency [RR 0.70, 95% CI: 0.51- 0.95] visits, with no statistically significant difference in endoscopic procedures, total health care encounters, corticosteroid use, and IBD related hospitalisation or surgery. The trials were judged to be at high risk of bias or to have some concerns for disease remission. The certainty of evidence was moderate or low., Conclusion: E-health technologies may have a role in value-based care in IBD., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Inflammatory bowel disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients., Methods: Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders, and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement., Results: In all, 31 members [15 gastroenterologists, 14 colorectal surgeons and two nurse specialists] from nine countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting., Conclusions: By consolidating evidence for best practice using literature review and key stakeholder and decision-making expert consultation, we have developed international consensus recommendations to support health care professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Despite advances in ulcerative colitis (UC) therapies, a relatively undefined proportion of patients experience faecal incontinence (FI) in the absence of active inflammation. For this group, there remains a significant unmet need with a limited evidence base., Aims: We aimed to estimate the prevalence and impact of FI in UC., Methods: In a prospective cross-sectional study, patients with UC completed a series of validated questionnaires, including Rome IV FI criteria, an inflammatory bowel disease (IBD)-specific FI questionnaire (ICIQ-IBD), Hospital Anxiety and Depression Scale and IBD-Control. UC remission was defined as faecal calprotectin (FCP) ≤250 μg/g, or IBD-control 8 score ≥13 and IBD-Control-VAS ≥ 85., Results: Of 255 patients with UC, overall, 20.4% fulfilled Rome IV criteria for FI. Rome IV FI prevalence did not differ between active and quiescent UC regardless of whether disease activity was defined by IBD-Control scores ± FCP (p = 0.25), or objectively with FCP thresholds of 250 μg/g (p = 0.86) and 100 μg/g (p = 0.95). Most patients (75.2%) reported FI when in 'remission' and during 'relapse' (90.6%) according to ICIQ-IBD. Those who reported FI according to both ICIQ-IBD and Rome IV definitions had higher anxiety, depression and worse quality-of-life (QoL) scores (p < 0.05). In those with Rome IV FI, there was a strong correlation between FI symptom severity and impaired QoL (r = 0.809, p < 0.001)., Conclusions: The prevalence of FI in UC is high, even in remission, and associated with significant psychological distress, symptom burden and impaired QoL. These findings highlight the urgent need for further research and development of evidence-based treatments for FI in UC., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Objective: Despite its association with poorer outcomes, opioid use in inflammatory bowel disease (IBD) is not well characterised in the UK. We aimed to examine the extent of opioid use, the associated factors and the use of mitigation techniques such as pain-service review and opioid weaning plans among individuals with IBD., Methods: Data were collected from consecutive patients attending IBD outpatient appointments at 12 UK hospitals. A predefined questionnaire was used to collect data including patient demographics, IBD history, opioid use in the past year (>2 weeks) and opioid-use mitigation techniques. Additionally, consecutive IBD-related hospital stays leading up to July 2019 were reviewed with data collected regarding opioid use at admission, discharge and follow-up as well as details of the admission indication., Results: In 1352 outpatients, 12% had used opioids within the past 12 months. Over half of these individuals were taking opioids for non-IBD pain and less than half had undergone an attempted opioid wean.In 324 hospitalised patients, 27% were prescribed opioids at discharge from hospital. At 12 months postdischarge, 11% were using opioids. Factors associated with opioid use in both cohorts included female sex, Crohn's disease and previous surgery., Conclusions: 1 in 10 patients with IBD attending outpatient appointments were opioid exposed in the past year while a quarter of inpatients were discharged with opioids, and 11% continued to use opioids 12 months after discharge. IBD services should aim to identify patients exposed to opioids, reduce exposure where possible and facilitate access to alternative pain management approaches., Competing Interests: Competing interests: SB has had speaker arrangements with Takeda and Dr Falk, has received travel grants from Galapagos, Celltrion and Dr Falk and has provided consultancy to Galapagos. JKL has received grants from Galapagos and Takeda and speaker and consultancy fees from Abbvie, Arena, Celltrion, Ferring, Galapagos, Janssen, MSD, Pfizer and Takeda. GP has had personal fees from AbbVie, Allergan, BMS, Celltrion, Ferring, Galapagos, Janssen, Takeda, Tillotts. Travel grants from—AbbVie, Celltrion, Ferring, Janssen, Takeda, Tillotts and is a Director and Shareholder in Ampersand Health. GS has had speaker arrangements with Takeda, Abbvie, Tillotts and Galapagos. TR has received research/educational grants and/or speaker/consultation fees from Abbvie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Roche, Sandoz, Takeda and UCB. CAL reports grants from Genentech, grants and personal fees from Janssen, grants and personal fees from Takeda, grants from AbbVie, personal fees from Ferring, grants from Eli Lilly, grants from Pfizer, grants from Roche, grants from UCB Biopharma, grants from Sanofi Aventis, grants from Biogen IDEC, grants from Orion OYJ, personal fees from Dr Falk Pharma, grants from AstraZeneca, outside the submitted work. NAK has served as a speaker and/or advisory board member for AbbVie, Allergan, BMS, Falk, Ferring, Galapagos, Janssen, Mylan, Pharmacosmos, Sandoz, Takeda and Tillotts. IC has speaker arrangements with Celltrion and has received a travel grant from Galapagos. RP has provided consultancy to Galapagos. CS has received unrestricted research grants from Warner Chilcott, Janssen and AbbVie, has provided consultancy to Warner Chilcott, Dr Falk, AbbVie, Takeda, Fresenius Kabi, Galapagos, Ferring, Arena and Janssen, and had speaker arrangements with Warner Chilcott, Dr Falk, AbbVie, MSD, Pfizer, Celltrion and Takeda.The preparation of this paper was funded in part by Galapagos., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Healthcare quality improvement (QI) is the systematic process to continuously improve the quality of care and outcomes for patients. The landmark Inflammatory Bowel Disease (IBD) UK National Audits provided a means to measure the variation in care, highlighting the need to define the standards of excellence in IBD care. Through a consensus approach, we aimed to establish key performance indicators (KPIs), providing reliable benchmarks for IBD care delivery in UK., Methods: KPIs that measure critical aspects of a patient journey within an IBD service were identified though stakeholder meetings. A two-stage Delphi consensus was then conducted. The first involved a multidisciplinary team of IBD clinicians and patients to refine definitions and methodology. The second stage assessed feasibility and utility of the proposed QI process by surveying gastroenterology services across UK., Results: First, the four proposed KPIs were refined and included time from primary care referral to diagnosis in secondary care, time to treatment recommendation following a diagnosis, appropriate use of steroids and advanced therapies prescreening and assessment. Second, the Delphi consensus reported >85% agreement on the feasibility of local adoption of the QI process and >75% agreement on the utility of benchmarking of the KPIs., Conclusions: Through a structured approach, we propose quantifiable KPIs for benchmarking to improve and reduce the individual variation in IBD care across the UK., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Anti-tumour necrosis factor (anti-TNF) agents are associated with increased infection risk among elderly inflammatory bowel disease (IBD) patients, and thus, alternative biologics may be preferable. However, little comparative data exist on the safety and efficacy of vedolizumab and ustekinumab in elderly IBD patients., Aims: To compare the safety and effectiveness of ustekinumab and vedolizumab in elderly Crohn's disease patients., Methods: Patients ≥ 60 years old who commenced ustekinumab or vedolizumab for Crohn's disease (CD) were included. Primary outcome was serious infections, defined as requiring hospitalisation. Efficacy was assessed by treatment persistence and clinical response rates. We appropriately adjusted for confounders using propensity score-matched analysis weighted by the inverse predicted probability of treatment weighing and performed a logistic regression analysis to assess factors associated with serious infections and treatment persistence., Results: Eighty-three patients commencing ustekinumab and 42 commencing vedolizumab therapy were included. In a propensity adjusted cohort, the rate of serious infection and treatment persistence were comparable between ustekinumab and vedolizumab. There was a significant reduction in HBI at 6 and 12 months compared to baseline in both groups. Male gender was positively associated with serious infection risk at 12 months, and penetrating disease behaviour was positively associated with 12-month treatment persistence. Baseline HBI score was negatively associated with 12-month treatment persistence. Cox regression analysis showed no overall difference in treatment discontinuation-free and serious infection-free survival by 12 months., Conclusions: We observed comparable safety and effectiveness for ustekinumab and vedolizumab in treating elderly CD patients., (© 2022. Crown.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Biologic and nonbiologic immunomodulators, used to treat immune-mediated inflammatory diseases (IMIDs), could impair the immune response to COVID-19 vaccines and thus vaccine effectiveness., Objectives: Our objective was to investigate the association between biologic and nonbiologic immunomodulators and seroconversion following the first and second dose of COVID-19 vaccines in patients with IMIDs., Methods: Serum samples were collected following the first or second dose of the BNT162b2 or AZD1222 vaccines from patients receiving biologic and/or nonbiologic immunomodulators for one or more of psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease or systemic lupus erythematosus. Seroconversion was defined as a positive Roche Elecsys® Anti-SARS-CoV-2 S (spike protein subunit S1/receptor binding domain) immunoassay (≥ 0.8 U mL-1). Association between immunomodulator exposure and seroconversion was assessed using logistic regression, adjusting for age and sex., Results: After excluding those with prior COVID-19, post-first vaccine dose samples from 193 participants and post-second dose samples from 312 participants were included in the analysis. Following the first vaccine dose, 17.6% (n = 34) of participants did not seroconvert. Seroconversion was reduced for those on nonbiologic [adjusted odds ratio (OR) 0.29, 95% confidence interval (CI) 0.12-0.69] or combined nonbiologic and biologic treatment (adjusted OR 0.14, 95% CI 0.045-0.45) compared with those on biologic monotherapy. Subgroup analysis demonstrated reduced odds of seroconversion in those on methotrexate (adjusted OR 0.097, 95% CI 0.19-0.49) or prednisolone treatment (adjusted OR 0.044, 95% CI 0.002-1.00) relative to tumour necrosis factor-α inhibitor monotherapy. No participants receiving rituximab (n < 5) seroconverted after the first vaccine dose. Following the second vaccine dose, 1.6% of all participants did not seroconvert. Non-seroconversion was associated with receiving rituximab (n = 3 of 4) compared with those receiving other therapies (n = 2 of 308, P < 0.001). Post hoc analyses demonstrated that non-seroconversion was associated with age [adjusted OR 0.18, 95% CI 0.037-0.93 for those aged 60 years and over (reference category age 18-39 years)], but not sex, ethnicity or vaccine type., Conclusions: Treatment with nonbiologics, particularly methotrexate, is associated with impaired seroconversion following two BNT162b2 or AZD1222 vaccine doses, in patients with IMIDs. These findings are consistent with those of other published studies. While this could indicate reduced protection against COVID-19, the immunological parameters that correlate most closely with vaccine effectiveness need to be defined to reach this conclusion., Competing Interests: Conflicts of interest A.A.-J. has received educational support from Janssen and UCB to attend conferences, and funding from the UK North West MRC Scheme, which is part funded by Eli Lilly, Novartis, Roche and UCB. A.C.F. has worked as a consultant for or received sponsorship to attend conferences from AbbVie, Almirall, Eli Lilly, LEO Pharma, Novartis, Pfizer, Janssen, Sanofi and UCB. H.J.A.H. has received grant funding from Janssen, Merck Serono and Pfizer; honoraria and/or consultancy fees and/or travel bursaries from AbbVie, Almirall, DICE Therapeutics, Eli Lilly, Janssen, La Roche-Posay, LEO Pharma, Novartis, Regeneron, Sanofi Genzyme, UCB and UNION Therapeutics; and has acted as an investigator for AbbVie, Almirall, DICE Therapeutics, Eli Lilly, Evelo Biosciences, Janssen, LEO Pharma, Novartis, Sanofi Genzyme, UCB and UNION Therapeutics. H.C. has received grant support from Eli Lilly and UCB; consulting fees from Alexion, AstraZeneca, Eli Lilly, Novartis and Orphazyme; and acted as a speaker for Biogen and UCB. K.L.H. has received honoraria and/or research funding from AbbVie, Bristol Myers Squibb and Pfizer. J.K.L. has received speaker and/or consultancy fees from AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Ferring Pharmaceuticals, Galapagos, Janssen, MSD, Takeda and Tillotts Pharma; and research funding from Galapagos, Takeda Pharmaceutical Company Ltd and Tillotts Pharma. C.E.M.G. has received honoraria and/or research funding from AbbVie, Amgen, Anaptysbio, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis and UCB. C.A.M. is an employee of Affinity Biomarker Labs. R.B.W. has acted as a consultant for or received research grants from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Astellas Pharma, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DICE Therapeutics, GSK, Janssen, Lilly, LEO Pharma, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB and UNION Therapeutics., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting., Methods: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents., Results: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively., Conclusion: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ulcerative colitis (UC) is a chronic relapsing and remitting gastrointestinal disorder of uncertain aetiology. The last two decades have seen an expansion in the therapeutic arsenal used to treat UC. This has resulted in improved clinical remission and response rates. Nonetheless, staples in our current medical management originate from trials conducted in the early 20th century. In this review article, we aim to outline the key milestones in the history of the medical management of UC in addition to highlighting promising therapeutic developments for the future., Competing Interests: The authors declare the following conflict of interests: SL: No conflict of interest to declare NA: No conflict of interest to declare RS: No conflict of interest to declare TB: No conflict of interest to declare JS: Has received speaker fees for Takeda, Abbvie and an unrestricted research grant from Tillots PJS: Has received speaker fees from Takeda, Janssen, Celltrion, Abbvie, Amgen, Dr Falk pharmaceuticals, Tillotts Pharma and has been an advisory board member for Abbvie, Celltrion, Galapagos and Janssen JKL: Has received speaker or consultancy fees from Abbvie, Arena, Galapagos, Janssen, MSD, Takeda, Pfizer and research grants from Takeda and Galapagos, (© The Author(s), 2022.)

Objective: Anti-tumour necrosis factor (TNF) agents are associated with increased infection risk among elderly IBD patients, but little is known about non anti-TNF biologics in this cohort. We examined the safety and effectiveness of ustekinumab in elderly Crohn's patients., Methods: This retrospective multi-centre cohort study included Crohn's patients ≥60-years old who commenced ustekinumab. We recorded Harvey-Bradshaw index (HBI), concomitant steroid therapy, treatment persistence and new infections or malignancies. Primary outcome was serious infections requiring hospitalisation., Results: Seventy patients were included, with median age of 68 years. 43 (61.4%) had prior anti-TNF exposure, and 15 (21.4%) vedolizumab. Median treatment duration was 12 months, totalling 84 patient-years. Nine serious infections were reported, incidence 106.7/1000 patient-years. Systemic steroids were associated with increased risk of serious infections [odds ratio (OR) 7.83, 95% confidence interval (CI): 1.44-44.32, P = 0.02]. There were 27 "non-serious" infections; 321.4/1000 patient-years. Charlson co-morbidity index (OR 1.49, 95% CI: 1.05-2.12, P = 0.03) and steroid exposure (OR 44.10, 95% CI: 1.75-1112.10, P = 0.02) increased non-serious infection risk (P &lt; 0.05). Mean HBI improved from 8.13 to 4.64 at 6 months and 4.10 at last follow up (P &lt; 0.0001). 12-month treatment persistence was 55.7% (N = 39); 34 (48.6%) were steroid-free., Conclusion: Ustekinumab was safe and effective in a cohort of elderly Crohn's disease patients. Infections were mostly mild, not resulting in therapy discontinuation. Serious infection risk was comparable to previously reported rates with anti-TNF agents. Steroid exposure was associated with an increased serious infection risk., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Competing interests: ‘Yes, there are competing interests for one or more authors and I have provided a Competing Interests statement in my manuscript and in the box below’

Inflammatory bowel diseases, comprising ulcerative colitis (UC) and Crohn's disease, are chronic, immune-mediated and progressive inflammatory disorders affecting the gastrointestinal tract. Tofacitinib is the first oral small-molecule Janus kinase (JAK) inhibitor licensed and approved by the National Institute for Health and Care Excellence (NICE) for use in moderately-to-severely active UC after intolerance, inadequate response, or loss of response to conventional treatment or biologic therapy. The pivotal OCTAVE studies demonstrated the efficacy and safety of tofacitinib for the induction and maintenance of remission in UC. A growing body of evidence from real-world data supports the positive clinical and endoscopic benefits observed with tofacitinib treatment in the OCTAVE trials. This narrative review summarizes the current literature regarding the mechanism of action of tofacitinib, data from registrational trials, emerging real-world evidence, and an overview of the most recent safety evidence. We explore evolving treatment paradigms, including the use of tofacitinib in the COVID-19 era, pregnancy and extraintestinal manifestations, as well as the emerging concept of combining tofacitinib with biological therapy. We will also present a brief overview of the next generation of JAK inhibitors in the pipeline., Competing Interests: Disclosure and potential conflicts of interest: EL and JKL have a non-pharmaceutical investigator-initiated sponsored research grant from Galapagos. EL has received speaker fees from Janssen. JKL has received speaker and consultancy fees from Abbvie, Arena, MSD, Galapagos, Janssen, Takeda, Pfizer and Tillots, and research support from Galapagos and Takeda. EL has received speaker fees from Janssen. The authors declare that they have no other conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2022/03/dic.2021-11-4-COI.pdf, (Copyright © 2022 Liu E, Aslam N, Nigam G, Limdi JK.)