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Background Dyslipidemia may be an important modifiable risk factor contributing to the increased cardiovascular risk in inflammatory bowel disease (IBD). The lipid metabolism is subject to both systemic inflammation and drug therapy; however, it is unclear if this effect is drug-class dependent. Our aim was to assess lipid changes after IBD induction therapy and evaluate associated factors with a particular focus on drug class and disease activity. Methods In this prospective study, consecutive IBD patients starting systemic therapy (eg, corticosteroids, thiopurines, methotrexate, anti-TNF-α agents, vedolizumab, ustekinumab, and tofacitinib) were included. Primary outcomes were changes in total cholesterol, high density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides at week 10. Results One hundred ninety-eight IBD patients (107 women [54%], median age 36 years; interquartile range [IQR], 27-47) were included: 137 Crohn’s disease (67%), 61 ulcerative colitis (29%), and 8 IBD-unclassified (4%). Median C-reactive protein and fecal calprotectin at baseline were 5.1 mg/L (IQR, 1.6-12.0) and 1040 ug/g (IQR, 383-1800), respectively. Relative increases in total cholesterol, HDL-c, and LDL-c were significant after prednisone (+26%, +31%, +12%) and tofacitinib therapy (+20%, +25%, +26%), respectively. Results remained after adjusting for concomitant corticosteroids, cholestyramine, and PSC diagnosis. Changes in clinical scores were inversely correlated with total cholesterol changes (R −186, P = .014), as was CRP with total cholesterol and LDL-c (R −0.292 and R −0.259, P < .001). No correlation was found with FCP. Lipid changes remained after adjusting for age and CRP. Conclusions Prednisone and tofacitinib induction therapy significantly increase serum lipid levels, whereas no changes were observed in other drug classes. The observations seem drug-specific inasmuch as adjustment for systemic inflammation did not alter the results.

Background: An unmet need remains for improved management in perianal fistulising Crohn's disease (pCD). Recently, local administration of adipose-derived cells has shown promising results. Aims: To assess the safety and feasibility of injection of stromal vascular fraction (SVF) with platelet-rich plasma (PRP) in patients with pCD. Methods: Patients ≥ 18 years with pCD were included and underwent fistula curettage, SVF with PRP injection, and closure of the internal opening. The primary endpoint was safety at 12 months. The secondary outcomes were complete radiological healing at 3 months (absence of fluid-containing tracts on MRI) and partial and complete clinical response at 3 and 12 months (closure of ≥1, respectively, all treated external opening(s)). Results: Twenty-five patients were included (35 [IQR 25–40] years; 14 [56%] female); median CD duration 4 [IQR 2–8] years. Twenty-four (95%) patients had previously undergone fistula surgery. No adverse events were encountered at lipoharvesting sites. Two (8%) patients were readmitted to hospital and six (24%) underwent unplanned re-interventions. Post-operative MRI (n = 24) showed complete radiological healing in nine (37.5%) patients. Partial clinical response was present in 48% (12/25) at 3 months and in 68% (17/25) at 12 months, and complete clinical closure in five (20%) patients at 3 months and in 10 (40%) patients at 12 months. Conclusion: Injection with autologous SVF with PRP is feasible and safe in patients with treatment-refractory pCD. Early complete radiological healing was observed in more than one-third of patients, and clinical response in two-thirds of patients at 12 months.

Background: Ustekinumab, a human immunoglobulin G1 monoclonal antibody that binds to and inhibits interleukin (IL)-12/IL-23, is indicated for multiple immune-mediated diseases. Ustekinumab is actively transported across the placenta and theoretically could impact pregnancy outcomes. Limited data on pregnancy outcomes with ustekinumab exposure are available. Aim: To assess pregnancy outcomes in patients exposed to ustekinumab during pregnancy. Methods: Cumulative data on medically confirmed ustekinumab-exposed pregnancies from the manufacturer's Global Safety Database were summarised. Descriptive data for pregnancy outcomes were presented overall and by patient subgroups. Results: As of 31 August 2020, 408 medically confirmed, prospective, maternal ustekinumab-exposed pregnancies with reported outcomes were identified. The mean maternal age was 31 years. Of the 420 pregnancy outcomes (including 4 sets of twins),a,b 340 (81%) were live births, 51 (12.1%) spontaneous abortions, 25 (6%) elective/induced abortions, 3 (0.7%) stillbirths and 1 (0.2%) ongoing pregnancy with foetal congenital anomaly (CA). Among 340 live births, 33 (9.7%) were born pre-term. The rate of major CAs was similar by indication (Crohn's disease vs psoriasis), ustekinumab dose (45 mg vs 90 mg) and timing and duration of maternal exposure to ustekinumab. Prospective outcomes of pregnancies with paternal periconceptional ustekinumab exposure (n = 87) included 92% live births (1.2% major CA), 5.7% spontaneous abortions and 2.3% elective/induced abortions. Conclusions: Rates of adverse pregnancy outcomes or CAs with ustekinumab exposure were consistent with rates reported for the US general population and do not suggest a higher risk associated with maternal or paternal exposure to ustekinumab.

Background To learn from the crisis caused by the coronavirus disease (COVID-19) pandemic and be prepared for future pandemics, it is important to investigate the impact of this period on the wellbeing of patients with inflammatory bowel disease (IBD). Aims To describe the health-related quality of life (HRQoL) and disease control of IBD patients during the first wave of the COVID-19 pandemic in The Netherlands. Methods Between March 17 and July 1, 2020, patients aged 18 years and older with IBD from the Erasmus MC (Rotterdam, The Netherlands) were invited to complete online questionnaires at week 0, 2, 6 and 12. The Inflammatory Bowel Disease Questionnaire (IBDQ), the Inflammatory Bowel Disease Control-8 (IBD-control-8) and the numeric rating scale on fatigue were used. The evolution of the different outcomes over time was measured using mixed models. Results Of 1151 invited patients, 851 patients (67% CD and 33% UC or IBD-U) participated in the study (response rate 74%). No relevant changes in total scores were found over time for the IBDQ (effect estimate 0.006, 95% CI [− 0.003 to 0.015]) and IBD-control-8 (effect estimate 0.004, 95% CI [0.998–1.011]). There was a slight, increasing trend in fatigue scores over time (effect estimate 0.011, 95% CI [0.004, 0.019]). Conclusions This first lock down due to the COVID-19 pandemic in The Netherlands did not impact on the HRQoL and disease control of patients with IBD. Up to date information may have contributed to a stable HRQoL in IBD patients even in an extreme period with restrictions and insecurities. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-021-07118-8.

Patients with Crohn’s disease (CD) are at a considerable risk for intestinal surgery. Approximately 25% of patients with CD will undergo an intestinal resection within 10 years of diagnosis. Postoperative complications after CD surgery have been reported in 20%-47% of the patients. Both general and CD-related risk factors are associated with postoperative complications, and comprise non-modifiable (e.g., age) and potentially modifiable risk factors (e.g., malnutrition). Prehabilitation focuses on the preoperative period with strategies designed to optimize modifiable risk factors concerning the physical and mental condition of the individual patient. The aim of prehabilitation is to enhance postoperative recovery and return to or even improve preoperative functional capacity. Preoperative improvement of nutritional status, physical fitness, cessation of smoking, psychological support, and critical revision of preoperative use of CD medication are important strategies. Studies of the effect on postoperative outcome in CD patients are scarce, and guidelines lack recommendations on tailored management. In this opinion review, we review the current evidence on the impact of screening and management of nutritional status, physical fitness, CD medication and laboratory values on the postoperative course following an intestinal resection in CD patients. In addition, we aim to provide guidance for individualized multimodal prehabilitation in clinical practice concerning these modifiable factors.

Aims Inflammatory bowel disease (IBD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). We compared cardiovascular disease (CVD) risk factors and 10-year risk in IBD patients to the general population. Methods and results In this cross-sectional study, consecutive IBD patients ≥45 years were included. History of ASCVD and CVD risk factors (smoking, hypertension, overweight, hypercholesterolaemia, diabetes, and metabolic syndrome) were assessed. The Systematic COronary Risk Evaluation (SCORE2) algorithm was used to estimate 10-year CVD risk. One to four age/sex-matched controls were derived from the prospective population-based Rotterdam Study cohort. In total, 235 IBD patients were included {56% women, median age 59 years [interquartile range (IQR) 51–66]} and matched to 829 controls [56% women, median age 61 years (IQR 56–67)]. Inflammatory bowel disease patients experienced ASCVD events more often compared with matched controls [odds ratio (OR) 2.01, 95% confidence interval (CI) 1.23–3.27], specifically heart failure (OR 2.02, 95% CI 1.02–4.01) and coronary heart disease (OR 2.01, 95% CI 1.7–3.13). Inflammatory bowel disease patients showed lower odds of overweight (OR 0.48, 95% CI 0.35–0.66) and hypercholesterolaemia (OR 0.45, 95% CI 0.31–0.65) and higher odds of hypertension (OR 1.67, 95% CI 1.19–2.32), as well as higher waist circumference (+4 cm, P = 0.006) and triglyceride levels (+0.6 mmol/L, P < 0.001) as compared with controls. Mean 10-year CVD risk was 4.0% [standard deviation (SD) ±2.6] in 135 IBD patients vs. 6.0% (SD ±1.6) in 506 controls. Conclusion The increased CVD risk in IBD is discrepant with the 10-year CVD risk estimate. Systematic COronary Risk Evaluation may underestimate CVD risk in IBD patients due to differing CVD risk profiles compared with the general population, including a lower prevalence of hypercholesterolaemia and overweight and a higher prevalence of hypertension, abdominal obesity, and hypertriglyceridaemia.

Item does not contain fulltext BACKGROUND: Despite its effectiveness in treating Crohn's disease, adalimumab is associated with an increased risk of infections and high health-care costs. We aimed to assess clinical outcomes of increased adalimumab dose intervals versus conventional dosing in patients with Crohn's disease in stable remission. METHODS: The LADI study was a pragmatic, open-label, multicentre, non-inferiority, parallel, randomised controlled trial, done in six academic hospitals and 14 general hospitals in the Netherlands. Adults (aged ≥18 years) diagnosed with luminal Crohn's disease (with or without concomitant perianal disease) were eligible when in steroid-free clinical and biochemical remission (defined as Harvey-Bradshaw Index [HBI] score

A considerable proportion of Crohn's disease patients that undergo ileocecal resection (ICR) have failed anti-tumor necrosis factor (TNF) therapy preoperatively. This study aimed to assess the effectiveness of retreatment of anti-TNF therapy in patients with postoperative recurrence.A real-world cohort study was performed on Crohn's disease patients who underwent primary ICR after anti-TNF therapy failure, and who were retreated with anti-TNF therapy for postoperative symptomatic Crohn's disease. The primary outcome was treatment failure (the need for (re)introduction of corticosteroids, immunosuppressants, or biologicals or the need for re-resection). Sub-analyses were performed on the nature of preoperative anti-TNF failure (primary non-response, secondary loss of response, intolerance), indication for ICR (refractory, stricturing, penetrating disease), combination therapy with immunomodulators, retreatment with the same anti-TNF agent and preoperative exposure to 1 vs.1 anti-TNF agents.In total, 66 of 364 patients retreated with anti-TNF therapy following ICR. Cumulative rates of treatment failure at 1 and 2 years were 28% and 47%. Treatment failure rate at 2 years was significantly lower in patients receiving combination therapy as compared to anti-TNF monotherapy (30% vs. 49%, P = 0.02). No difference in treatment failure was found with regards to the nature of preoperative anti-TNF failure (P = 0.76), indication for ICR (P = 0.88) switch of anti-TNF agent (P = 0.55) agent, and preoperative exposure to 1 vs.1 anti-TNF agents (P = 0.88).Retreatment with anti-TNF therapy for postoperative Crohn's disease recurrence is a valid strategy after preoperative failure. Combination therapy is associated with a lower rate of treatment failure.

Background: Increase in lipid levels associated with the treatment of inflammatory bowel disease (IBD) has previously been reported. However, it is unknown if this effect is similar for all IBD drug classes.Aim: To precisely assess the effect of different IBD drug classes on lipid profilesMethods: We performed a systematic literature search of randomised controlled trials and observational cohort studies that assessed lipid levels before and after induction (10 weeks) of IBD treatment. Data of 11 studies (1663 patients) were pooled using random effects models. The influence of patient and disease characteristics on treatment effects on total cholesterol levels was analysed in 6 studies (1211 patients) for which individual data were available, using linear mixed models.Results: A statistically significant increase in total cholesterol was observed after induction treatment with corticosteroids (+1.19 mmol/L, 95% confidence interval [CI95] +0.52 to +2.59), and tofacitinib (+0.66 mmol/L, CI95 +0.42 to +0.79), but not after anti-TNF alpha treatment (-0.11 mmol/L, CI95 -0.26 to +0.36 mmol/L). Similar differences were observed after maintenance treatment. Treatment effects were significantly related to age, but not with other factors. Lipid changes were inversely correlated with but not modified by CRP changes.Conclusions: Increase in total cholesterol levels was strongest for corticosteroids followed by tofacitinib but was not observed for anti-TNF alpha agents. Whether total cholesterol change associated with IBD treatment has an effect on cardiovascular risk requires further study.

Background: Therapeutic drug monitoring (TDM) is important in optimizing use of biologics in inflammatory bowel diseases (IBD). However, the role of proactive TDM during remission remains uncertain. Methods: This retrospective study included patients receiving infliximab (IFX) therapy at Massachusetts General Hospital or Erasmus University Medical Center. All eligible patients had completed induction phase of IFX and were in clinical and endoscopic remission. Our primary outcome was clinical relapse within 2 years after baseline. Multivariable regression models examined the association between infliximab trough levels during remission and relapse, need for IBD-related surgery or hospitalization. Results: Our study cohort included 110 patients with IBD (72 CD, 38 UC) on IFX maintenance therapy. In total, 12 patients (10.9%) experienced relapse of disease over 2 years. The mean IFX trough level at baseline was 8.0 µg/mL (± 8.6) and did not differ between the institutions. 49.1% of patients had levels < 5 µg/mL and 2.7% had antibodies to infliximab at baseline. There was no difference in the mean IFX trough levels between patients who relapsed (7.5 µg/mL ± 3.7 µg/mL) over 24 months compared to those who did not (8.1 µg/mL ± 7.9 µg/mL, p = 0.815). On multivariable logistic regression analysis, IFX trough levels at baseline were not associated with relapse of disease over 24 months (OR 1.01, 95% CI 0.93–1.09, p = 0.856). Conclusion: This retrospective multicenter study provides evidence that IFX trough levels during quiescent disease do not predict relapse over 2 years, suggestive that proactive TDM in this setting is not warranted.

OBJECTIVES Disease knowledge is important in adolescents with inflammatory bowel disease (IBD) transitioning to adult care. We developed an IBD-specific knowledge questionnaire, the Rotterdam Transition Test (RTT), and aimed to validate this tool. METHODS This is a prospective longitudinal validation study. The RTT has 25 open questions on IBD, medication, lifestyle and transition to adult care. A scoring model was developed, and inter-rater agreement was assessed. Using a Rasch model, we determined the difficulty and performance of the questions. Cronbach's alpha was used to demonstrate reliability. Patient factors (age, disease, education, medication use, illness acceptance and independence) were correlated to RTT score. RESULTS A total of 207 RTTs were evaluated in 111 adolescent IBD patients. The scoring model showed a kappa score of > 0.61 for all questions. Reliability with Cronbach's alpha was good (0.81). Mean total result of the RTT was 58% (females) and 55% (males) of maximal score.The RTT discriminated well between the different levels of knowledge. Knowledge scores increased in patients who did repeated RTTs during the transition period. Male sex, low educational level, disease acceptance issues and dependence on parents associated with a significantly lower total RTT score. Prednisone use within three months and treatment without biologics associated with significantly higher RTT scores. Disease activity was not a significant factor. CONCLUSION The Rotterdam Transition Test is a reliable and valid tool to assess IBD knowledge. The RTT can be used to detect and discuss knowledge gaps in adolescents with IBD transitioning to adult healthcare. An infographic is available for this article at:http://links.lww.com/MPG/C472.

BACKGROUND AND AIMS: Current guidelines recommend endoscopic resection of visible and endoscopically resectable colorectal colitis-associated neoplasia (CAN) in patients with inflammatory bowel disease (IBD). However, patients with high-risk CAN (HR-CAN) are often not amenable to conventional resection techniques, and a consensus approach for the endoscopic management of these lesions is presently lacking. This Delphi study aims to reach consensus among experts on the endoscopic management of these lesions. METHODS: A 3-round modified Delphi process was conducted to reach consensus among worldwide IBD and/or endoscopy experts (n = 18) from 3 continents. Consensus was considered if ≥75% agreed or disagreed. Quality of evidence was assessed by the criteria of the Cochrane Collaboration group. RESULTS: Consensus was reached on all statements (n = 14). Experts agreed on a definition for CAN and HR-CAN. Consensus was reached on the examination of the colon with enhanced endoscopic imaging before resection, the endoscopic resectability of an HR-CAN lesion, and endoscopic assessment and standard report of CAN lesions. In addition, experts agreed on type of resections of HR-CAN (< 20 mm, >20 mm, with or without good lifting), endoscopic success (technical success and outcomes), histologic assessment, and follow-up in HR-CAN. CONCLUSIONS: This is the first step in developing international consensus-based recommendations for endoscopic management of CAN and HR-CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of CAN and HR-CAN. The present work and proposed standardization might benefit future studies. ispartof: GASTROINTESTINAL ENDOSCOPY vol:97 issue:4 ispartof: location:United States status: published

BACKGROUND Despite enormous clinical improvements, due to better management strategies and the availability of biologicals, immune-mediated inflammatory diseases (IMIDs) still have a significant impact on patients’ lives. To further reduce disease burden, provider- as well as patient-reported outcomes (PROs) should be taken into account during treatment and follow-up. Web-based collection of these outcomes generates valuable repeated measurements, which could be used (1) in daily clinical practice for patient-centered care, including shared decision-making; (2) for research purposes; and (3) as an essential step toward the implementation of value-based health care (VBHC). Our ultimate goal is that our health care delivery system is completely aligned with the principles of VBHC. For aforementioned reasons, we implemented the IMID registry. OBJECTIVE The IMID registry is a digital system for routine outcome measurement that mainly includes PROs to improve care for patients with IMIDs. METHODS The IMID registry is a longitudinal observational prospective cohort study within the departments of rheumatology, gastroenterology, dermatology, immunology, clinical pharmacy, and outpatient pharmacy of the Erasmus MC, the Netherlands. Patients with the following diseases are eligible for inclusion: inflammatory arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, uveitis, Behçet disease, sarcoidosis, and systemic vasculitis. Generic and disease-specific (patient-reported) outcomes, including adherence to medication, side effects, quality of life, work productivity, disease damage, and activity, are collected from patients and providers at fixed intervals before and during outpatient clinic visits. Data are collected and visualized through a data capture system, which is linked directly to the patients’ electronic health record, which not only facilitates a more holistic care approach, but also helps with shared decision-making. RESULTS The IMID registry is an ongoing cohort with no end date. Inclusion started in April 2018. From start until September 2022, a total of 1417 patients have been included from the participating departments. The mean age at inclusion was 46 (SD 16) years, and 56% of the patient population is female. The average percentage of filled out questionnaires at baseline is 84%, which drops to 72% after 1 year of follow-up. This decline may be due to the fact that the outcomes are not always discussed during the outpatient clinic visit or because the questionnaires were sometimes forgotten to set out. The registry is also used for research purposes and 92% of the patients with IMIDs gave informed consent to use their data for that. CONCLUSIONS The IMID registry is a web-based digital system that collects provider- and PROs. The collected outcomes are used to improve care for the individual patient with an IMID and facilitate shared decision-making, and they are also used for research purposes. The measurement of these outcomes is an essential step toward the implementation of VBHC. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/43230

Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). The increased risk of CVD concerns an increased risk of venous thromboembolism (VTE), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), at corresponding relative risks of 2.5, 1.2 and 2.0, respectively, as compared with the general population. Especially young patients under the age of 40 years run a relatively high risk of these complications when compared with the general population. Chronic systemic inflammation causes a hypercoagulable state leading to the prothrombotic tendency characteristic of VTE, and accelerates all stages involved during atherogenesis in ASCVD. Increased awareness of VTE risk is warranted in patients with extensive colonic disease in both ulcerative colitis and Crohn’s disease, as well as during hospitalization, especially when patients are scheduled for surgery. Similarly, critical periods for ASCVD events are the 3 months prior to and 3 months after an IBD-related hospital admission. The increased ASCVD risk is not fully explained by an increased prevalence of traditional risk factors and includes pro-atherogenc lipid profiles with high levels of small dense low-density lipoprotein cholesterol particles and dysfunctional high-density lipoprotein cholesterol. Risk factors associated with HF are location and extent of inflammation, female sex, and age exceeding 40 years. A dose-dependent increase of overall CVD risk has been reported for corticosteroids. Immunomodulating maintenance therapy might reduce CVD risk in IBD, not only by a direct reduction of chronic systemic inflammation but possibly also by a direct effect of IBD medication on platelet aggregation, endothelial function and lipid and glucose metabolism. More data are needed to define these effects accurately. Despite accumulating evidence on the increased CVD risk in IBD, congruent recommendations to develop preventive strategies are lacking. This literature review provides an overview of current knowledge and identifies gaps in evidence regarding CVD risk in IBD, by discussing epidemiology, pathogenesis, and clinical management.

Summary Background Knowledge of the cost of illness of inflammatory bowel disease (IBD) is essential for health policy makers worldwide. Aim To assess the cost of illness of IBD from the societal perspective taking into account time trends and geographical differences. Methods A systematic review of all population‐based studies on cost of illness of IBD published in Embase, Medline, Web of Science and Google Scholar. Methodology of included studies was assessed and costs were adjusted to 2018 US dollars. Results Study methodologies differed considerably, with large differences in perspective, valuation method and population. For prevalent Crohn's disease (CD) cases in the last ten years annual healthcare costs were in Asia $4417 (range $1230‐$31 161); Europe $12 439 ($7694‐$15 807) and North America $17 495 ($14 454‐$20 535). For ulcerative colitis (UC), these were $1606 ($309‐$14 572), $7224 ($3228‐$9779) and $13 559 ($13 559‐$13 559). The main cost driver was medication, the cost of which increased considerably between 1985 and 2018, while outpatient and inpatient costs remained stable. IBD had a negative impact on work productivity. Annual costs of absenteeism for CD and UC were in Asia (with presenteeism) $5638 ($5638‐$5638) and $4828 ($4828‐$4828); Europe $2660 ($641‐$5277) and $2394 ($651‐$5992); North America $752 ($307‐$1303) and $1443 ($85‐$2350). Conclusion IBD societal cost of illness is increasing, driven by growing costs of medication, and varies considerably between continents. While biologic therapy was expected to decrease inpatient costs by reducing hospitalisations and surgery, these costs have not declined., Costs of IBD are increasing due to biologics and vary between continents. Biologics do not reduce inpatient costs.

Aims Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin [IL]-12 and IL-23. It is registered for the treatment of inflammatory bowel diseases. We assessed the 2-year effectiveness and safety of ustekinumab in a real world, prospective cohort of patients with Crohn’s disease [CD]. Methods Patients who started ustekinumab were prospectively enrolled in the nationwide Initiative on Crohn and Colitis [ICC] Registry. At weeks 0, 12, 24, 52 and 104, clinical remission Harvey Bradshaw Index≤ 4 points], biochemical remission (faecal calprotectin ≤ 200 μg/g and/or C-reactive protein ≤5 mg/L], perianal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. The primary outcome was corticosteroid-free clinical remission at week 104. Results In total, 252 CD patients with at least 2 years of follow-up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission was 32.3% [81/251], 41.4% [104/251], 39% [97/249] and 34.0% [84/247] at weeks 12, 24, 52 and 104, respectively. In patients with combined clinical and biochemical disease activity at baseline [n = 122], the corticosteroid-free clinical remission rates were 23.8% [29/122], 35.2% [43/122], 40.0% [48/120] and 32.8% [39/119] at weeks 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks in all patients was 64.3% and 54.8%, respectively. The main reason for discontinuing treatment after 52 weeks was loss of response [66.7%]. No new safety issues were observed. Conclusion After 104 weeks of ustekinumab treatment, one-third of CD patients were in corticosteroid-free clinical remission.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC. ispartof: GASTROENTEROLOGY vol:163 issue:4 pages:950-964 ispartof: location:United States status: published

Inflammatory bowel disease has a high incidence and prevalence especially in young individuals in their reproductive years. Trying to conceive and being pregnant is an emotional period for those involved. In the majority of patients suffering from inflammatory bowel disease, maintenance therapy is required during pregnancy to control the disease, and disease control might necessitate introduction of new drugs during a vulnerable period. Therefore, the management of patients with a wish to conceive and during pregnancy requires specialized counselling and appropriate management including a multidisciplinary approach and close involvement of the prospective parents under a shared decision-making model. This updated consensus paper addresses these issues and is aimed to optimize pre-conceptional, pregnancy and post pregnancy counselling, including the monitoring and therapeutic management of patients with IBD patients with a wish to conceive. ispartof: JOURNAL OF CROHNS & COLITIS vol:17 issue:1 pages:1-27 ispartof: location:England status: published

Background & Aims The superiority of anti-TNF-α agents to thiopurines for the prevention of postoperative recurrence of Crohn’s disease (CD) after ileocolonic resection remains controversial. In this meta-analysis of individual participant data (IPD), the effect of both strategies was compared and assessed after risk stratification. Methods After a systematic literature search, IPD were requested from randomized controlled trials investigating thiopurines and/or anti-TNF-α agents after ileocolonic resection. Primary outcome was endoscopic recurrence (ER) (Rutgeerts score ≥i2) and secondary outcomes were clinical recurrence (Harvey-Bradshaw Index/Crohn’s Disease Activity Index score) and severe ER (Rutgeerts score ≥i3). A fixed effect network meta-analysis was performed. Subgroup effects were assessed and a prediction model was established using Poisson regression models, including sex, smoking, Montreal classification, CD duration, history of prior resection and previous exposure to anti-TNF-α or thiopurines. Results In the meta-analysis of IPD, 645 participants from 6 studies were included. In the total population, a superior effect was demonstrated for anti-TNF-α compared with thiopurine prophylaxis for ER (relative risk [RR], 0.52; 95% confidence interval [CI], 0.33–0.80), clinical recurrence (RR, 0.50; 95% CI, 0.26–0.96), and severe ER (RR, 0.41; 95% CI, 0.21–0.79). No differential subgroup effects were found for ER. In Poisson regression analysis, previous exposure to anti-TNF-α and penetrating disease behavior were associated with ER risk. The advantage of anti-TNF-α agents as compared with thiopurines was observed in low- and high-risk groups. Conclusions Anti-TNF-α is superior to thiopurine prophylaxis for the prevention of endoscopic and clinical postoperative CD recurrence after ileocolonic resection. The advantage of anti-TNF-α agents was confirmed in subgroup analysis and after risk stratification.

BackgroundInflammatory bowel disease (IBD) has a major impact on different aspects of life of patients with IBD, but functioning in the home environment is under-reported in literature. The aim of this study was to assess the impact of IBD on household and/or family life.MethodAdult patients with IBD from the outpatient clinic of the Erasmus MC (Rotterdam, the Netherlands) were invited to participate in this cross-sectional study between September and December 2020. A questionnaire was composed to measure the impact of IBD on functioning in the household and family life. In addition, the IBD Disability Index and Work Productivity and Activity Impairment Questionnaire were used. Data were analysed using descriptive statistics and multiple logistic regression modelling.ResultsOf 308 invited patients, 229 patients were included (response rate 74%). Sixty-eight per cent of patients were diagnosed with Crohn’s disease, 69% were female and median age was 38.0 years. Many patients reported difficulties with domestic activities (55.0%), leisure (53.9%), parenting (50.6%), sexual activities (48.4%) and interpersonal relationships (39.1%). Fatigue was associated with the experience of more severe difficulties in domestic activities (OR 16.160, 95% CI 6.053 to 43.141). Furthermore, 32.7% of patients felt that IBD influenced their desire to have children.ConclusionIBD has a markedly negative impact on household and/or family life in many patients. To optimise patient care, household and family related difficulties need to be considered in a holistic treatment approach.

Background and Aims The long-term safety and efficacy of allogeneic bone marrow-derived mesenchymal stromal cell [bmMSC] therapy in perianal Crohn’s disease [CD] fistulas is unknown. We aimed to provide a 4-year clinical evaluation of allogeneic bmMSC treatment of perianal CD fistulas. Methods A double-blind dose-finding study for local bmMSC therapy in 21 patients with refractory perianal fistulising Crohn’s disease was performed at the Leiden University Medical Center in 2012–2014. All patients treated with bmMSCs [1 x 107 bmMSCs cohort 1, n = 5; 3 × 107 bmMSCs cohort 2, n = 5; 9 × 107 bmMSCs cohort 3, n = 5] were invited for a 4-year evaluation. Clinical events were registered, fistula closure was evaluated, and anti-human leukocyte antigen [HLA] antibodies were assessed. Patients were also asked to undergo a pelvic magnetic resonance imaging [MRI] and rectoscopy. Results Thirteen out of 15 patients [87%] treated with bmMSCs were available for long-term follow-up. Two non-MSC related malignancies were observed. No serious adverse events thought to be related to bmMSC therapy were found. In cohort 2 [n = 4], all fistulas were closed 4 years after bmMSC therapy. In cohort 1 [n = 4] 63%, and in cohort 3 [n = 5] 43%, of the fistulas were closed, respectively. In none of the patients anti-HLA antibodies could be detected 24 weeks and 4 years after therapy. Pelvic MRI showed significantly smaller fistula tracts after 4 years. Conclusions Allogeneic bmMSC therapy for CD-associated perianal fistulas is also in the long-term a safe therapy. In bmMSC-treated patients, fistulas with closure at Week 24 were still closed after 4 years.

Influenza vaccination can be less effective in patients treated with immunosuppressive therapy. However, little is known about the effects of ustekinumab, an anti-IL-12/23 agent used to treat Crohn&rsquo, s disease (CD), on vaccination response. In this prospective study, we assessed immune responses to seasonal influenza vaccination in CD patients treated with ustekinumab compared to CD patients treated with anti-TNF&alpha, therapy (adalimumab) and healthy controls. Humoral responses were assessed with hemagglutinin inhibition (HI) assays. Influenza-specific total CD3+, CD3+CD4+, and CD3+CD8+ T-cell responses were measured with flow cytometry. Fifteen patients treated with ustekinumab, 12 with adalimumab and 20 healthy controls were vaccinated for seasonal influenza in September 2018. Seroprotection rates against all vaccine strains in the ustekinumab group were high and comparable to healthy controls. Seroconversion rates were comparable, and for A/H3N2 highest in the ustekinumab group. HI titers were significantly higher in the ustekinumab group and healthy controls than in the adalimumab group for the B/Victoria strain. Post-vaccination T-cell responses in the ustekinumab group were similar to healthy controls. One-month post-vaccination proliferation of CD3+CD8+ T-cells was highest in the ustekinumab group. In conclusion, ustekinumab does not impair immune responses to inactivated influenza vaccination. Therefore, CD patients treated with ustekinumab can be effectively vaccinated for seasonal influenza

BACKGROUND: Low-dose thiopurine-allopurinol (LDTA) combination therapy is a commonly applied optimisation strategy in IBD patients with a skewed thiopurine metabolism.AIM: To assess continued LDTA maintenance treatment at annual intervals and explore risk factors for treatment cessation METHODS: Adult IBD patients treated with LDTA between 2009 and 2016 were retrospectively included. Data on the incidence of clinical and laboratory adverse events (AEs), including hepatotoxicity and myelotoxicity resulting in imposing LDTA therapy cessation and associated risk factors were collected.RESULTS: In total, 221 IBD patients (46% male, median age 42 years) were included. Maintenance LDTA treatment was continued in 78% of patients at 1 year (n = 145), 66% at 2 years (n = 83), 57% at 3 years (n = 52) and 52% at 4 years (n = 33). Treatment in patients receiving LDTA therapy for AEs during thiopurine monotherapy was more often continued than in patients initiating LDTA for other indications (eg, ineffectiveness of thiopurine monotherapy, routinely discovered skewed metabolism) (P = 0.016). Myelotoxicity during thiopurine monotherapy resolved in 87% and hepatotoxicity in 86% after median of 1.2 and 1.4 months after LDTA initiation. Cumulative incidence of AEs during LDTA resulting in therapy cessation within total follow-up of 449 treatment-years was 7% for clinical AEs, 4% for myelotoxicity and 1% for hepatotoxicity.CONCLUSION: LDTA therapy is a safe and beneficial optimisation strategy in IBD patients. Continued maintenance LDTA treatment is 52% after 4 years of treatment and most commonly affected by ineffectiveness of LDTA rather than LDTA-attributed toxicity. LDTA optimisation strategy is most advantageous in patients failing thiopurine monotherapy due to AEs.

This randomized trial studied the effect of cognitive behavioral therapy (CBT) for the treatment of subclinical anxiety and/or depression on disease course in young IBD patients. CBT did not influence time to relapse, clinical disease activity, C-reactive protein or calprotectin levels., Background Anxiety and depressive symptoms are prevalent in patients with inflammatory bowel disease (IBD) and may negatively influence disease course. Disease activity could be affected positively by treatment of psychological symptoms. We investigated the effect of cognitive behavioral therapy (CBT) on clinical disease course in 10–25-year-old IBD patients experiencing subclinical anxiety and/or depression. Methods In this multicenter parallel group randomized controlled trial, IBD patients were randomized to disease-specific CBT in addition to standard medical care (CBT + care us usual [CAU]) or CAU only. The primary outcome was time to first relapse in the first 12 months. Secondary outcomes were clinical disease activity, fecal calprotectin, and C-reactive protein (CRP). Survival analyses and linear mixed models were performed to compare groups. Results Seventy patients were randomized (CBT+CAU = 37, CAU = 33), with a mean age of 18.3 years (±50% < 18 y, 31.4% male, 51.4% Crohn’s disease, 93% in remission). Time to first relapse did not differ between patients in the CBT+CAU group vs the CAU group (n = 65, P = 0.915). Furthermore, clinical disease activity, fecal calprotectin, and CRP did not significantly change over time between/within both groups. Exploratory analyses in 10–18-year-old patients showed a 9% increase per month of fecal calprotectin and a 7% increase per month of serum CRP in the CAU group, which was not seen in the CAU+CBT group. Conclusions CBT did not influence time to relapse in young IBD patients with subclinical anxiety and/or depression. However, exploratory analyses may suggest a beneficial effect of CBT on inflammatory markers in children.

Background & aims: It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs. Methods: Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index–matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared among healthy cotwins, IBD-twins, unrelated patients with IBD, and healthy controls with multivariable (ie, adjusted for potential confounding) generalized linear models. Results: No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate

Therapeutic drug monitoring (TDM) is important in optimizing use of biologics in inflammatory bowel diseases (IBD). However, the role of proactive TDM during remission remains uncertain.This retrospective study included patients receiving infliximab (IFX) therapy at Massachusetts General Hospital or Erasmus University Medical Center. All eligible patients had completed induction phase of IFX and were in clinical and endoscopic remission. Our primary outcome was clinical relapse within 2 years after baseline. Multivariable regression models examined the association between infliximab trough levels during remission and relapse, need for IBD-related surgery or hospitalization.Our study cohort included 110 patients with IBD (72 CD, 38 UC) on IFX maintenance therapy. In total, 12 patients (10.9%) experienced relapse of disease over 2 years. The mean IFX trough level at baseline was 8.0 µg/mL (± 8.6) and did not differ between the institutions. 49.1% of patients had levels 5 µg/mL and 2.7% had antibodies to infliximab at baseline. There was no difference in the mean IFX trough levels between patients who relapsed (7.5 µg/mL ± 3.7 µg/mL) over 24 months compared to those who did not (8.1 µg/mL ± 7.9 µg/mL, p = 0.815). On multivariable logistic regression analysis, IFX trough levels at baseline were not associated with relapse of disease over 24 months (OR 1.01, 95% CI 0.93-1.09, p = 0.856).This retrospective multicenter study provides evidence that IFX trough levels during quiescent disease do not predict relapse over 2 years, suggestive that proactive TDM in this setting is not warranted.

Contains fulltext : 220106.pdf (Publisher’s version ) (Closed access) BACKGROUND: To timely detect myelotoxicity and hepatotoxicity, laboratory monitoring at 3-month intervals is advised throughout thiopurine maintenance treatment for IBD. However, reported incidence rates of myelotoxicity and hepatotoxicity in maintenance treatment are low. AIM: To assess incidence rates and clinical consequences of myelotoxicity and hepatotoxicity in thiopurine maintenance therapy after at least 1 year of thiopurine treatment. METHODS: Retrospective analysis of therapy adjustment for laboratory toxicity in adult IBD patients after 12 consecutive months of azathioprine (AZA) or mercaptopurine monotherapy (ie baseline) between 2000 and 2016. Incidence rates of laboratory toxicity (ie myelotoxicity [leucocyte count

Contains fulltext : 220028.pdf (Publisher’s version ) (Open Access) Prospective data of vedolizumab treatment for patients with inflammatory bowel disease (IBD) beyond 1 year of treatment is scarce but needed for clinical decision making. We prospectively enrolled 310 patients with IBD (191 with Crohn's disease (CD) and 119 patients with ulcerative colitis (UC)) with a follow-up period of 104 weeks (interquartile range: 103-104) in a nationwide registry. The corticosteroid-free clinical remission rate (Harvey Bradshaw Index ≤ 4, Short Clinical Colitis Activity index ≤ 2) at weeks 52 and 104 were 28% and 19% for CD and 27% and 28% for UC, respectively. Fifty-nine percent maintained corticosteroid-free clinical remission between weeks 52 and 104. Vedolizumab with concomitant immunosuppression showed comparable effectiveness outcomes compared with vedolizumab monotherapy (week 104: 21% vs. 23%; P = 0.77), whereas 8 of 13 severe infections occurred in patients treated with concomitant immunosuppression. To conclude, the clinical effect was 19% for CD and 28% for UC after 2 years of follow-up regardless of concomitant immunosuppression.

Background Transition programmes are designed to prepare adolescent inflammatory bowel disease [IBD] patients for transfer to adult care. It is still unclear which outcome parameters define ‘successful transition’. Therefore, this study aimed to identify outcomes important for success of transition in IBD. Methods A multinational Delphi study in patients, IBD nurses, and paediatric and adult gastroenterologists was conducted. In stage 1, panellists commented on an outcome list. In stage 2, the refined list was graded from 1 to 9 [least to very important], by an expert and a patient panel. In stage 3, the expert panel ranked important outcomes from 1 to 10 [least to most important]. Descriptive statistics and Mann–Whitney U-tests were performed. Results The final item list developed in stage 1 was tested by the expert [n = 74 participants, 52.7% paediatric] and patient panel [n = 61, aged 16–25 years, 49.2% male]. Respectively, ten and 11 items were found to be important by the expert and patient panel. Both panels agreed on eight of these items, of which six reflected self-management skills. In stage 3, the expert panel formed a top-ten list. The three most important items were: decision-making regarding IBD [mean score 6.7], independent communication [mean score 6.3] and patient satisfaction [mean score 5.8]. Conclusion This is the first study identifying outcomes that IBD healthcare providers and patients deem important factors for successful transition. Self-management skills were considered more important than IBD-specific items. This is a first step to further define success of transition in IBD and subsequently evaluate the efficacy of different transition models.

Objective Postoperative endoscopic recurrence in patients with Crohn's disease (CD) is commonly classified using the Rutgeerts score. Ulcerations in the ileal blind loop are not taken into account in the Rutgeerts score, and the clinical relevance of these lesions is unknown. This study aimed to assess the outcome of isolated ileal blind loop inflammation (IBLI) in postoperative CD patients. Methods Adult CD patients who underwent intestinal surgery with ileocolonic anastomosis between 1997 and 2017 were included and postoperative endoscopy reports were retrospectively reviewed. IBLI was defined as isolated inflammation of the ileal blind loop with or without ulcera confined to the anastomosis. Outcome was assessed using endoscopic recurrence (Rutgeerts >i2) and surgical recurrence (re-resection). Results A total of 341 CD patients were included. In 125 out of 341 (37%) patients, the ileal blind loop was described in the endoscopy reports. IBLI was reported in 43 of 341 (13%) patients. Start or step-up drug therapy was initiated in 10 of 32 (31%) IBLI patients with abdominal symptoms within a median of 0.9 months [interquartile range (IQR) 0.7-1.4] after ileocolonoscopy. Endoscopic recurrence occurred in 4 out of 38 (11%) IBLI patients without re-resection, within a median of 12.4 months (IQR 6.8-13.3). Intestinal re-resection was performed in 5 out of 43 (16%) IBLI patients within a median of 3.7 months (IQR 3.5-10.8). Conclusion IBLI is associated with symptoms and an unfavorable outcome, with a high risk of endoscopic recurrence in the neoterminal ileum and intestinal re-resection during short-term follow-up. Therefore, the blind ileal loop needs to be assessed during endoscopy in postoperative CD patients.

Fatigue is an important clinical problem in patients with IBD, affecting nearly 50% of patients in clinical remission and > 80% of those with active disease. The resulting decrease in quality of life and impaired work productivity and functioning contribute markedly to the societal costs of fatigue. However, despite the burden and effects of fatigue, little is known about its aetiology and pathophysiology, which impairs our ability to effectively treat this symptom. Here, we review the theories behind the development of fatigue in IBD and the role of contributing factors, including nutritional deficiency, inflammation and altered metabolism. We also explore the potential role of the gut microbiome in mediating fatigue and other psychological symptoms through the gut–brain axis. We discuss the efficacy of nutrient repletion and various psychological and pharmacological interventions on relieving fatigue in patients with IBD and expand the discussion to non-IBD-related fatigue when evidence exists. Finally, we present a therapeutic strategy for the management of fatigue in IBD and call for further mechanistic and clinical research into this poorly studied symptom. Fatigue is an important problem for patients with IBD, but little is known about its pathophysiology. In this Review, the authors explore the epidemiology, putative mechanisms and optimal management of this symptom.

Background The risk of gallstone disease necessitating cholecystectomy after ileal resection (IR) in Crohn’s disease (CD) patients is not well established. We studied the incidence, cumulative and relative risk of cholecystectomy after IR in CD patients, and associated risk factors. Methods CD patients with a first IR between 1991 and 2015 were identified in PALGA, a nationwide pathology database in the Netherlands. Details on subsequent cholecystectomy and IR were recorded. Yearly cholecystectomy rates from the general Dutch population were used as a reference. Results A cohort of 8302 (3466 (41.7%) males) CD patients after IR was identified. During the 11.9 (IQR 6.3–18.0) years median follow-up, the post-IR incidence rate of cholecystectomy was 5.2 (95% CI 3.5–6.4)/1000 persons/year. The cumulative incidence was 0.5% at 1 year, 2.4% at 5 years, 4.6% at 10 years, and 10.3% after 20 years. In multivariable analyses, female sex (HR 1.9, CI 1.5–2.3), a later calendar year of first IR (HR/5-year increase, HR 1.27, CI 1.18–1.35), and ileal re-resection (time-dependent HR 1.37, CI 1.06–1.77) were associated with cholecystectomy. In the last decade, cholecystectomy rates increased and were higher in our postoperative CD population than in the general population (relative incidence ratio 3.13 (CI 2.29–4.28; p

Background and Aims: Pregnancy guidelines for women with inflammatory bowel disease [IBD] provide recommendations regarding anti-TNF cessation during pregnancy, in order to limit foetal exposure. Although infliximab [IFX] leads to higher anti-TNF concentrations in cord blood than adalimumab [ADA], the recommendations are similar. We aimed to demonstrate the effect of anti-TNF cessation during pregnancy on foetal exposure, for IFX and ADA separately. Methods: We conducted a prospective single-center cohort study. Women with IBD, using IFX or ADA, were followed-up during pregnancy. In case of sustained disease remission, anti-TNF was stopped in the third trimester. At the birth, the anti-TNF concentration was measured in the cord blood. A linear regression model was developed to demonstrate anti-TNF concentration in cord blood at birth. In addition, outcomes such as disease activity, pregnancy outcomes and 1-year health outcomes of infants were collected. Results: We included 131 pregnancies that resulted in a live birth [73 IFX, 58 ADA]. At birth, 94 cord blood samples were obtained [52 IFX, 42 ADA], showing significantly higher levels of IFX than ADA [p < 0.0001]. Anti-TNF type and stop week were used in the linear regression model. During the third trimester, IFX transportation over the placenta increased exponentially; however ADA transportation was limited and increased in a linear fashion. Overall, health outcomes were comparable. Conclusions: Our linear regression model shows that ADA may be continued longer during pregnancy, because transportation over the placenta is lower than for IFX. This may reduce relapse risk of the mother, without increasing foetal anti-TNF exposure.

Background and Aims: Success in delivering value-based healthcare involves measuring outcomes that matter most to patients. Our aim was to develop a minimum Standard Set of patient-centred outcome measures for inflammatory bowel disease (IBD), for use in different healthcare settings. Methods: An international working group (n=25) representing patients, patient associations, gastroenterologists, surgeons, specialist nurses, IBD registries and patient-reported outcome measure (PROM) methodologists participated in a series of teleconferences incorporating a modified Delphi process. Systematic review of existing literature, registry data, patient focus groups and open review periods were used to reach consensus on a minimum set of standard outcome measures and risk adjustment variables. Similar methodology has been used in 21 other disease areas (www.ichom.org). Results: A minimum Standard Set of outcomes was developed for patients (aged ≥16) with IBD. Outcome domains included survival and disease control (survival, disease activity/remission, colorectal cancer, anaemia), disutility of care (treatment-related complications), healthcare utilisation (IBD-related admissions, emergency room visits) and patient-reported outcomes (including quality of life, nutritional status and impact of fistulae) measured at baseline and at 6 or 12 month intervals. A single PROM (IBD-Control questionnaire) was recommended in the Standard Set and minimum risk adjustment data collected at baseline and annually were included: demographics, basic clinical information and treatment factors. Conclusions: A Standard Set of outcome measures for IBD has been developed based on evidence, patient input and specialist consensus. It provides an international template for meaningful, comparable and easy-to-interpret measures as a step towards achieving value-based healthcare in IBD. (248 words).

Introduction Neonates exposed to tumour necrosis factor [TNF] alpha inhibitors in utero are born with detectable drug levels which can still be detected throughout the first year of life. Since 2011, the hepatitis B virus [HBV] vaccine is routinely administered to all newborns in the Netherlands. Adults treated with anti-TNF have been reported to respond inadequately to the HBV vaccine. The aim of this study was to compare anti-HB levels in anti-TNF-exposed children with non-exposed children following routine Dutch HBV vaccination. Methods We performed a cross-sectional, controlled cohort study from 2014 to 2017 in a single, tertiary referral centre. Pregnant women treated with anti-TNF for inflammatory bowel disease [IBD] and their subsequent children were recruited from the IBD preconception outpatient clinic. Pregnant women not treated with anti-TNF for IBD and their subsequent children were eligible as controls. Adherence to the Dutch National Vaccination Programme was mandatory for participation in this study. A venous blood sample was obtained 1 month after final HBV vaccination. Anti-HB levels were measured by enzyme-linked immunosorbent assay. Results Anti-HB levels at 12 months did not differ between the anti-TNF-exposed [n = 15] and the control group [n = 12] [> 1000 IU/l vs > 1000 IU/l, p = 0.59]. All children were successfully immunized against HBV, defined as anti-HB > 10 IU/l. Median anti-TNF levels determined in cord blood at birth were 9.0 µg/ml [interquartile range: 3.0-15.0 µg/ml] for infliximab and 0.4. µg/ml [interquartile range: 0.3-0.6 µg/ml] for adalimumab. There were no differences in general birth and health outcomes. Conclusion Children born with detectable anti-TNF levels can be effectively vaccinated against HBV.