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Background: The relationship between subcutaneous infliximab [SC-IFX] concentrations and favourable therapeutic outcomes in patients with Crohn's disease [CD] and ulcerative colitis [UC] remains elusive., Patients and Methods: This cross-sectional study included consecutive adult patients with inflammatory bowel disease [IBD] treated with SC-IFX at a maintenance dose of 120 mg/2 weeks. Investigated therapeutic outcomes included sustained clinical remission; composite clinical and biomarker remission [clinical remission and C-reactive protein <5 mg/L]; biochemical remission [faecal calprotectin <250 µg/g]; and deep remission [clinical, biological, and biochemical remission]., Results: Of 91 patients identified, 71 qualified for inclusion in the study [70% with CD; 27% with concomitant immunomodulators]. At the time of drug concentration measurement [median 13.5 months after switch], 55 [77%] patients had sustained clinical remission; n = 44 [62%] composite clinical and biomarker remission; n = 40 [56%] biochemical remission; and n = 31 [43%] deep remission. The mean SC-IFX concentrations were significantly higher in patients with sustained clinical remission [p = 0.014]; composite clinical and biomarker remission [p = 0.003]; biochemical remission [p < 0.001]; and deep remission [p < 0.001] compared to patients without having these outcomes. In multivariate analysis, SC-IFX concentration was the only factor independently associated with sustained clinical remission (odds ratio [OR]: 4.7, 95% confidence interval [CI]: 3.1-12.2, p = 0.005); clinical and biomarker remission [OR: 9.21, 95% CI: 6.09-18.7, p = 0.006]; biochemical remission [OR: 37, 95% CI: 14-39.3, p < 0.001]; and deep remission [OR: 29, 95% CI: 15.7-37.4, p < 0.001]. The optimal SC-IFX concentration cut-off associated with deep remission based on ROC analysis was 20 µg/mL [sensitivity: 0.91, specificity: 0.80, accuracy: 0.85]. Combination with an immunomodulator failed to improve SC-IFX pharmacokinetics., Conclusion: Higher SC-IFX concentrations are associated with higher rates of favourable therapeutic outcomes in IBD patients. Serum SC-IFX concentrations >20 µg/mL were significantly associated with deep remission., (© The Author(s) 2023. 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: Fatigue is commonly reported by patients with inflammatory bowel disease [IBD], but the determinants of IBD-related fatigue have yet to be determined., Aims: To identify the factors associated with fatigue in a large population of patients with IBD., Patients and Methods: Fatigue and nine other IBD-related disability dimensions were assessed in a cohort of 1704 consecutive patients with IBD using the IBD-disk questionnaire in a cross-sectional survey of 42 French and Belgian centres. Fatigue and severe fatigue were defined as energy subscores >5 and >7, respectively. Determinants of fatigue were assessed using univariate and multivariate analyses (odds ratios [ORs] are provided with 95% confidence intervals)., Results: The prevalence rates of fatigue and severe fatigue were 54.1% and 37.1%, respectively. Both fatigue and severe fatigue were significantly higher in patients with active disease than in patients with inactive disease [64.9% vs 44.7% and 47.4% vs 28.6%, respectively; p < 0.001 for both comparisons]. In the multivariate analysis stratified by age, sex, type of IBD and IBD activity, fatigue was associated with age >40 years (OR = 0.71 [0.54-0.93]), female sex (OR = 1.48 [1.13-1.93]) and IBD-related sick leave (OR = 1.61 [1.19-2.16]), and joint pain (OR = 1.60 [1.17-2.18]), abdominal pain (OR = 1.78 [1.29-2.45]), regulating defecation (OR = 1.67 [1.20-2.32]), education and work (OR = 1.96 [1.40-2.75]), body image (OR = 1.38 [1.02-1.86]), sleep (OR = 3.60 [2.66-4.88]) and emotions (OR = 3.60 [2.66-4.88]) subscores >5., Conclusion: Determinants of fatigue are not restricted to IBD-related factors but also include social factors, sleep and emotional disturbances, thus supporting a holistic approach to IBD patient care., (© 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.)

Many patients with inflammatory bowel disease [IBD] are treated with anti-tumour necrosis factor [TNF] therapies, of which infliximab [IFX] is most commonly used. Loss of response [LOR] to anti-TNF therapy due to immunogenic failure accounts for 20% of subsequent medical intervention and is defined, using a drug-sensitive assay, as low or undetectable concentration of drug with high titres of anti-drug antibodies [ADAb]. We performed a systematic review to investigate the use of a drug-tolerant assay during both induction and maintenance, to monitor patients treated with anti-TNFs. After the search on PubMed, 90 publications were reviewed. Most ADAb detection methods are drug-sensitive, cannot detect ADAb in the presence of drug, and therefore cannot be used close to drug administration when the drug concentration is too high. To overcome this major limitation, several drug-tolerant techniques have been developed and will be discussed in this review. Using drug-tolerant assays, ADAb against IFX or adalimumab [ADM] can be detected during induction and predict primary non-response or LOR. Drug-sensitive assays do not allow detection of ADAb during the induction phase when IFX or ADM concentration is typically high., (© 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.)

Background and Aims: Optimal management of patients with inflammatory bowel disease [IBD] after anti-tumour necrosis factor [TNF] discontinuation due to severe induced skin lesions is unclear. Our study aimed to describe dermatological and IBD evolution after anti-TNF discontinuation for this side effect., Methods: We conducted a multicentre retrospective study including consecutive IBD patients who discontinued anti-TNF due to severe induced skin lesions. Our objectives were to determine factors associated with dermatological remission [complete disappearance of skin lesions] and with IBD relapse in patients with inactive disease at inclusion, notably the impact of an early switch to another biological agent within 3 months of anti-TNF discontinuation., Results: Among the 181 patients [134 women, 160 Crohn's disease] included in the 13 participating centres, dermatological remission occurred in 110 [62%] patients with a median [interquartile range, IQR] interval of 8.0 [6.8-11.0] months. Scalp location was independently associated with less remission of skin lesions (hazard ratio [HR] = 0.64 [95% CI 0.43-0.94], p = 0.02) while early switch was independently associated with a higher probability of remission of skin lesions (HR = 1.64 [95% CI 1.1-2.5], p = 0.02). Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 [51%] patients with a median [IQR] interval of 26.0 [23.0-39.1] months. Survival rates without IBD relapse at 1 year were 85.8% [95% CI 77.5-94.9] in the early switch group and 59.3% [95% CI 48.9-71.9] in the other group [p < 0.01]., Conclusions: Early switch to a new biological is associated with a higher probability of healing of anti-TNF-induced skin lesions and significantly reduces the risk of IBD relapse., (© 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.)

Background: Real life data regarding pharmacokinetics of vedolizumab in patients needing dose optimisation are scarce. We set to examine whether pre-optimisation vedolizumab levels associate with therapy outcomes and which mechanisms explain the associations., Methods: A multicentre observational study assessed the outcome of dose increase in association with pre-escalation levels in vedolizumab-treated patients. SubsequentIy, α4β7 occupancy on peripheral blood [PB] and intestinal lamina propria [LP] tissues was investigated on various cellular subsets in patients undergoing lower endoscopy on infusion day. Cellular localisation of vedolizumab-bound α4β7 and effects on M1 and M2 macrophages were also explored., Results: A total of 161 inflammatory bowel disease [IBD] patients were included. Among 129/161 patients intensified during maintenance [Week 14 onward], pre-intensification trough levels were comparable or higher among those subsequently attaining post-optimisation clinical, biomarker, and endoscopic remission, compared with non-remitting patients [p = 0.09, 0.25, 0.04, respectively]. Similar results were demonstrated for those dose-optimised during induction [Week 6, n = 32]. In the immune sub-study [n = 43], free α4β7 receptors at trough were similarly low among patients with/without mucosal healing, on PB T cells [p = 0.15], LP T cells [p = 0.88], and on PB eosinophils [p = 0.08]. Integrin receptors on M1 and M2 macrophages were also saturated by low levels of vedolizumab and anti-inflammatory cytokine secretion was not increased. Co-localisation and dissociation experiments demonstrated membranal α4β7 receptors of two origins: non-internalised and newly generated α4β7, but re-binding was still complete at very low concentrations., Conclusions: These results do not support pharmacokinetics as the mechanism responsible for loss of response to vedolizumab, nor do they support a need for higher drug concentration to enhance vedolizumab's immune effects. Higher pre-escalation levels may indicate less clearance [less severe disease] and higher likelihood of subsequent re-gained response, regardless of therapy escalation., (© The Author(s) 2021. 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 and Aim: The inflammatory bowel disease [IBD]-disk is a 10-item self-questionnaire that is used to assess IBD-related disability. The aim of the present study was to evaluate this tool in the assessment of IBD daily-life burden., Methods: A 1-week cross-sectional study was conducted in 42 centres affiliated in France and Belgium. Patients were asked to complete the IBD-disk [best score: 0, worst score: 100] and a visual analogue scale [VAS] of IBD daily-life burden [best score: 0, worst score: 10]. Analyses included internal consistency, correlation analysis, and diagnostic performance assessment., Results: Among the 2011 IBD outpatients who responded to the survey [67.8% of the patients had Crohn's disease], 49.9% were in clinical remission. The IBD-disk completion rate was 73.8%. The final analysis was conducted in this population [n = 1455 patients]. The mean IBD-disk score and IBD daily-life burden VAS were 39.0 ± 23.2 and 5.2 ± 2.9, respectively. The IBD-disk score was well correlated with the IBD daily-life burden VAS [r = 0.67; p <0.001]. At an optimal IBD-disk cut-off of 40, the area under the receiver operating characteristic curve [AUROC] for high IBD daily-life burden [VAS >5] was 0.81 (95% confidence interval [CI]: 0.79-0.83; p <0.001)., Conclusions: In a large cohort of patients, the IBD-disk score was well correlated with IBD daily-life burden, and it could be used in clinical practice., (© The Author(s) 2020. 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: Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease., Methods: The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%., Results: A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0-42.1%] vs 7% [0-18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]., Conclusions: These findings support the set-up of education programmes in centres involved in the management of IBD patients., (© The Author(s) 2020. 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.)

Introduction: The approved maintenance regimens for ustekinumab in Crohn's disease (CD) are 90 mg every 8 or 12 weeks. Some patients will partially respond to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections., Methods: All patients with active CD, as defined by Harvey-Bradshaw score ≥ 4 and one objective sign of inflammation (CRP > 5 mg/L and/or fecal calprotectin > 250 µg/g and/or radiologic and/or endoscopic evidence of disease activity) who required ustekinumab dose escalation to 90mg every 4 weeks for loss of response or incomplete response to ustekinumab 90mg every 8 weeks were included in this retrospective multicenter cohort study., Results: One hundred patients, with a median age of 35 years (Interquartile Range (IQR), 28 - 49) and median disease duration of 12 (7 - 20) years were included. Dose intensification was performed after a median of 5.0 (2.8 - 9.0) months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 (1.3 - 3.0) months. After a median follow-up of 8.2 (5.6-12.4) months, 61% of patients were still treated with ustekinumab, and 26% in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission (no ulcers). At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events., Conclusion: In this multicenter study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks., (© The Author(s) 2020. 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 and Aim: It is unclear whether vedolizumab therapy can be discontinued in patients with inflammatory bowel disease [IBD] after achieving steroid-free clinical remission. The aim was to assess the risk of relapse after vedolizumab therapy was discontinued., Methods: This was a retrospective observational study, collecting data from 21 tertiary centres affiliated with the GETAID from January 2017 to April 2019. Consecutive patients with IBD, who were in steroid-free clinical remission for at least 3 months and were treated with vedolizumab for at least 6 months, were included at the time of vedolizumab discontinuation., Results: A total of 95 patients [58 with Crohn's disease] discontinued vedolizumab after a median duration of therapy of 17.5 [10.6-25.4] months. After a median follow-up period of 11.2 [5.8-17.7] months, 61 [64%] patients experienced disease relapse. The probabilities of relapse-free survival were 83%, 59%, and 36% at 6, 12, and 18 months, respectively. According to the multivariate analysis, a C-reactive protein level less than 5 mg/L at vedolizumab discontinuation (hazard ratio [HR] = 0.56, 95% confidence interval [CI] [0.33-0.95], p = 0.03) and discontinuation due to patients' elective choice (HR = 0.41, 95% CI [0.21-0.80], p = 0.009) were significantly associated with a lower risk of relapse. Re-treatment with vedolizumab was noted in 24 patients and provided steroid-free clinical remission in 71% and 62.5% at Week 14 and after a median follow-up of 11.0 [5.4-13.3] months, respectively, without any infusion reactions., Conclusions: In this retrospective study, two-thirds of patients with IBD treated with vedolizumab experienced relapse within the first year after vedolizumab discontinuation. Re-treatment with vedolizumab was effective in two-thirds of patients., (Copyright © 2020 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Biologic therapies have revolutionized the management of inflammatory bowel disease [IBD], but primary and secondary non-responses occur in a significant proportion of patients. Therapeutic drug monitoring [TDM] now has an established role in the treatment algorithm for managing secondary loss of response to anti-tumour necrosis factor [anti-TNF] agents during maintenance therapy. Data to support the use of TDM in the management of secondary loss of response to vedolizumab and ustekinumab are emerging. The potential to prevent primary non-response to biologic agents during induction is of equal, and potentially greater, clinical importance. Again, most data supporting the use of 'proactive' TDM during induction pertains to the use of anti-TNF agents, but signals of efficacy for the use of TDM during induction with other biologic classes are now appearing. This review aims to summarize data on the use of TDM during induction to prevent pharmacokinetic primary non-response to all three classes of biologic therapy currently available for the treatment of IBD., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Adalimumab is administered via a pre-filled syringe or spring-loaded pen. In a previous study in Crohn's disease, higher drug levels were observed in syringe users. The aim of this study was to evaluate the impact of delivery device on adalimumab drug levels in patients with Crohn's disease., Methods: Consecutive Crohn's disease patients treated with maintenance adalimumab [40 mg fortnightly] were recruited from five centres. The first recorded drug level with matched clinical and biochemical markers of disease activity was compared between pen and syringe users., Results: Of 218 patients, 64% used pen, with a median faecal calprotectin 110 μg/g and serum C-reactive protein 4 mg/L. In comparison to pen, syringe users had higher albumin [39 vs 42 g/L; p = 0.016], lower Harvey-Bradshaw Index [2 vs 1; p = 0.017], and higher rates of concomitant immunomodulation [54% vs 71%; p = 0.014]. Drug levels were equivalent between pen and syringe users [median 5.3 vs 5.2 μg/ml; p = 0.584], even after controlling for disease activity and immunomodulation. Syringe users at Alfred Health had higher drug levels than pen [6.1 vs 4.5 μg/ml; p = 0.039]; a greater proportion achieved therapeutic levels [75% vs 44%; p = 0.045]. A higher proportion of pen users from Saint-Étienne had therapeutic levels [79% vs 42%; p = 0.027], yet no significant difference in drug levels [7.9 vs 4.5 μg/ml; p = 0.119]., Conclusions: Delivery device does not appear to significantly affect adalimumab drug levels. Given differences between study sites, studies evaluating administration education and technique are warranted., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

doi:10.1093/ecco-jcc/jjy222 Abstract P528 from the 'Poster presentations' section of the main abstract book has been withdrawn and re-inserted as DOP63 in the 'Late-breaking abstracts' section., (© The Author(s) 2019. 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 and Aims: Vedolizumab [VDZ], a humanized monoclonal antibody targeting α4β7 integrin, is effective in induction and maintenance therapy in patients with inflammatory bowel disease [IBD] who have not adequately responded to standard therapies, and high vedolizumab trough levels [VTLs] have been associated with clinical remission. The α4β7 integrin binds to endothelial MAdCAM-1 and is upregulated by retinoic acid [RA]. The aim of this study was to determine the relationships between soluble MAdCAM-1 [sMAdCAM-1] and RA concentrations during clinical remission with VDZ maintenance therapy., Methods: In a retrospective study performed in IBD patients treated with VDZ, we measured VTL, sMAdCAM-1 and RA concentrations., Results: Among the 62 included patients [38 Crohn's disease], 24 relapsed and 38 stayed in remission from Weeks 10 to 30 after VDZ initiation. During this maintenance therapy, the median values of VTLs and RA were 15.4 µg/mL and 0.97 ng/mL, respectively, whereas sMAdCAM-1 was undetectable [<0.41 ng/mL] in 67.3% of samples. The positive predictive value [PPV] of undetectable sMAdCAM-1 for clinical remission was 80.0%, with a corresponding sensitivity of 74.6%. On multivariate analysis, undetectable sMAdCAM-1 and high VTLs [>19 µg/mL] were independently associated with clinical remission [OR = 7.5, p = 0.006 and OR = 2.2, p = 0.045, respectively]. The combination of sMAdCAM-1 < 0.41 ng/mL and VTL > 19 µg/mL was the best pharmacokinetic profile, with a PPV of 95.2%. Median values of sMAdCAM-1 and RA were significantly higher [p = 0.0001] before VDZ therapy than during the follow-up [sMAdCAM-1: 40.5 vs < 0.41 ng/mL; RA: 1.7 vs 0.97 ng/mL]. Only RA > 1.86 ng/mL before VDZ therapy was predictive of clinical remission during the follow-up (Area Under a Receiver Operating Characteristic curve [AUROC] = 80.7%)., Conclusions: Undetectable sMAdCAM-1 appears strongly associated with clinical remission during VDZ maintenance therapy. Combination of undetectable sMAdCAM-1 with high VTL is also potentially interesting for therapeutic drug monitoring. Baseline RA concentrations are predictive of clinical remission. These findings need to be confirmed in further prospective studies., (Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aim: The aim of this survey was to find out the patients' perspectives concerning biosimilars., Methods: An online survey consisting of 14 questions was made available between November 2014 and October 2015. Only respondents who had heard of biosimilars were asked to respond the final twelve questions., Results: A total of 1181 patients responded. Of these, 38% had heard of biosimilars. The respondents worried about biosimilars' safety profile [47.0%], efficacy [40.3%], and molecular basis [35.0%]. Only 25.2% of the respondents had no concerns about biosimilars. Just over half [55.9%] of the respondents thought that the lower cost of the biosimilars should not come before their safety and efficacy. Only 12.5% of respondents felt that extrapolation made sense. The survey showed that 39.9% felt that patients should be systematically informed, and 26.7% felt that patient associations should be informed and able to give their opinions. It also revealed that 20.9% of the respondents would be against the idea of interchangeability if the patient was not aware; 65.7% of the respondents would want to know whether they were receiving the reference drug or the biosimilar, and have all necessary information in writing before the drug was administered. Only 31.0% of the respondents would be fully confident about biosimilars, even if they were prescribed and explained by the treating physician., Conclusions: Most patients were not familiar with biosimilars, and those who were had doubts and concerns about the biosimilars' safety and efficacy. The patients wished to be informed and involved in decision-making concerning biosimilars., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Anti-tumour necrosis factor [TNF] therapy in combination with thiopurine is the most effective strategy for Crohn's disease, but raises safety concerns., Methods: In a retrospective multicentre study, we investigated long-term outcome of patients starting anti-TNF monotherapy for Crohn's disease and investigated whether introducing an immunomodulator in patients losing response to anti-TNF monotherapy is effective for resetting immunogenicity., Results: A total of 350 adult patients with Crohn's disease received either infliximab [n = 178, 51%] or adalimumab [n = 172, 49%] monotherapy. Mean duration of follow-up was 42 months. An immunomodulator was initiated in 53 patients [15%]. At last follow-up, 73.1% [n = 38] were in clinical remission [one patient with missing data]. Multivariate analysis identified anti-TNF type [higher need for starting immunomodulator for infliximab than for adalimumab; p = 0.0058] and first- vs second-/third-/fourth-line anti-TNF therapy [p = 0.014] as predictors of immunomodulator initiation. Among the 18 patients with available data, introduction of an immunomodulator was able to restore infliximab trough level within the therapeutic range and to induce clinical remission in 10 patients [55%]. Cumulative probability of remaining on anti-TNF therapy was 57.9% at 5 years among the 297 patients not starting an immunomodulator during follow-up., Conclusion: An immunomodulator was initiated in 15% of patients with Crohn's disease starting anti-TNF monotherapy. Independent predictors of immunomodulator initiation were infliximab use and second-/third-/fourth-line anti-TNF therapy. Resetting immunogenicity with an immunomodulator was effective in half of patients in a sub-study. Persistence of anti-TNF treatment at 5 years was observed in half of the 297 patients not starting an immumodulator in a real-life setting., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Antibodies to infliximab [ATI] and trough levels to infliximab [TRI] are associated with loss of response in inflammatory bowel diseases [IBD]. The best way to predict loss of response [LOR] to infliximab [IFX] is unknown., Methods: We conducted a prospective observational cohort study enrolling all IBD patients who were in clinical remission at Week 14 after IFX treatment initiation. TRI, ATI and C-reactive protein [CRP] level were measured at Week 22 [T1] and thereafter at every other IFX infusion. Loss of clinical response was defined by a flare requiring therapeutic change [IFX dose intensification, initiation of another drug class, and/or surgery]., Results: A total of 93 patients [59 Crohn's disease, mean duration of follow-up 17.2 months] were included; 32 patients [34.4%] lost clinical response during follow-up. Cumulative probability of LOR was 50% at 20 months. Mean TRI at T1 was significantly lower in IBD patients with stable ATI as compared with those with transient ATI or without ATI [0.052, 3.34 ,and 4.29 µg/ml, respectively; p = 0.001 between no ATI vs stable ATI, and p = 0.005 between stable and transient ATI] [p = 0.0001]. Three independent factors were predictive of LOR after Cox proportional hazards modelling: TRI > 5.5 µg/ml (hazard ratio [HR]: 0.21; 95% confidence interval [CI]: 0.05-0.89;p = 0.034) at T1, CRP > 5mg/l [HR: 2.5; 95% CI: 1.16-5.26; p = 0.019] at T1, and stable ATI defined by two consecutive ATI > 20ng/ml [HR: 3.77; 95% CI: 1.45-10.0; p = 0.007]. Transient ATI did not influence LOR., Conclusions: LOR can be predicted based on a combination of CRP, TRI and stable ATI with a high degree of accuracy., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA] antibodies for diagnosis of inflammatory bowel disease [IBD], differentiation between Crohn's disease [CD] and ulcerative colitis [UC], disease stratification including IBD phenotype, and also for determination of the course of the disease, remain unclear., Methods: A large panel of serological anti-glycan carbohydrate antibodies, including anti-mannobioside IgG antibodies [AMCA], anti-chitobioside IgA [ACCA], anti-laminaribioside IgG antibodies [ALCA], anti-laminarin [anti-L] and anti-chitine [anti-C] were measured in the serum from a cohort of 195 patients with IBD] [107 CD and 88 UC]. The respective accuracy of isolated or combined markers for diagnosis, disease differentiation, stratification disease phenotype, and severity of the disease course, defined by a wide panel of criteria obtained from the past medical history, was assessed., Results: The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls [p < 0.0001 and p < 0.0007, respectively]. Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD in comparison with UC (area under receiver operating characteristic curve [AUROC] = 0.70 for each], the adjunction of anti-laminarin antibody substantially improved the differentiation between CD and UC [AUROC = 0.77]. Titres of ACCA [> 51U/ml] and anti-laminarin [> 31U/ml] were significantly linked with a higher association with steroid dependency (odds ratio [OR] =2.0 [1.0-4.0], p = 0.03 and OR = 2.4 [1.1-5.2], p = 0.02, respectively]. We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA > 77U/ml [OR = 4.3; p = 0.002], ASCA > 63U/ml [OR = 3.5; p < 0.009] and at a lesser degree ACCA > 50U/ml [OR = 2.8; p < 0.02] and severe UC course was significantly associated with AMCA > 52U/ml [OR = 3.4; p = 0.04] and ACCA > 25U/ml [OR = 3.0; p < 0.04]., Conclusions: Anti-glycan antibodies are valuable serological markers, especially AMCA antibodies that may help clinicians to promptly classify patients into high risk for severe disease., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Long-term benefits of combination therapy (combotherapy) with infliximab (IFX) and azathioprine (AZA) have been less studied in ulcerative colitis (UC) than in Crohn's disease. The aim of the present study was to determine UC disease activity in patients who received at least 6 months of combotherapy, and whether cotreatment for more than 6 months was useful in these patients., Methods: A retrospective multicenter study was conducted in seven French academic centers from January 2010 to September 2012, including all UC patients having received at least 6 months of combotherapy in prolonged remission off steroids. During the follow-up period, which was divided into trimesters, scheduled IFX was continued as maintenance and AZA could be withdrawn. Assessment of UC activity by trimester was based on the following events: disease relapse defined by clinical relapse requiring a change of treatment, IFX failure, and colectomy., Results: Eighty-two patients were included (mean age 38 years; male:female ratio 1:1) and followed up for a median of 22.3±14.0 months. Comparing 393 trimesters of combotherapy with 282 trimesters of IFX alone, fewer clinical relapses were observed with combotherapy (p = 0.049). Similar results were observed for IFX failure (p = 0.048). No difference was observed for colectomy. Duration of combotherapy longer than 9 months was inversely associated with clinical relapse (hazard ratio = 0.32 [95% confidence interval 0.15-0.70])., Conclusions: UC patients treated with combotherapy should maintain IFX and AZA for at least 9 months. Further studies are required to determine the optimal duration of combotherapy before stopping AZA in this situation., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aim: In patients with inflammatory bowel disease (IBD) tolerating 2-h infusions of 5mg/kg infliximab scheduled maintenance therapy, the infusion time can be shortened to 1-h with good tolerability. A retrospective study with small sample size demonstrated the feasibility of 1-hour infusion time for 10mg/kg infliximab in IBD patients., Methods: Between November 2011 and July 2012, 63 patients received 1-hour 10mg/kg infliximab infusions under standard operating procedures and were enrolled in a prospective observational study. Intravenous steroid premedication was given to all patients., Results: Sixty-three IBD patients on infliximab maintenance therapy (43 Crohn's disease, 34 males) received 1-hour 10mg/kg infusions during the study period. A total of 182 infliximab infusions were administered. Seventeen (26%) patients were receiving concomitant immunomodulators. Two patients experienced (2/182, 1%) severe acute infusion reactions consisting on a cutaneous lupus and one severe anaphylactic reaction. We also observed one (1/182, 0.5%) severe delayed reaction after the first 1-hour infliximab infusion consisting on acne generalis. All 3 reactions led to infliximab discontinuation. No mild acute reactions and 6 mild delayed reactions (6/182, 3%) occurred., Conclusions: In patients with IBD receiving infliximab scheduled maintenance therapy, 1-hour infusion time for 10mg/kg infliximab seems to be well tolerated. This option might be considered in clinical practice in order to decrease the extra-burden of infliximab infusions in this patient population., (© 2013.)

Background and Aims: About one-third of inflammatory bowel disease (IBD) patients still require surgery. A growing number of them receive anti-tumor necrosis factor (TNF) therapy before surgery. The present meta-analysis studied the risk of postoperative complications in IBD patients treated with anti-TNF., Methods: MEDLINE was searched (up to January 2012) to identify observational studies reporting the prevalence of postoperative complications in IBD patients. The prevalence of overall, infectious, and non-infectious postoperative complications was extracted for all studies, and according to preoperative anti-TNF treatment where reported. Pooled prevalence, as well as odds ratios (ORs), with 95% confidence intervals (CIs) was calculated., Results: The search identified 86 citations. Twenty-one studies, containing 4251 subjects, reported the prevalence of postoperative complications according to preoperative anti-TNF treatment. Pooled prevalence of any postoperative complication was 21%, 35%, and 26% in Crohn's disease (CD), ulcerative colitis (UC) or inflammatory bowel disease unspecified (IBD-U) and IBD, respectively. The prevalence of any postoperative complication was increased in IBD patients who underwent preoperative anti-TNF therapy (OR: 1.25; 95% CI: 1.02-1.53). Pooled prevalence of infectious postoperative complications was 16%, 17%, and 15% in CD, UC/IBD-U and IBD, respectively. The prevalence of infectious postoperative complications was increased in CD patients who underwent preoperative anti-TNF therapy (OR: 1.45; 95% CI: 1.03-2.05). The confounding effect of concomitant therapies could not be studied., Conclusions: Preoperative anti-TNF use slightly increases the occurrence of overall postoperative complications in IBD patients, and particularly infectious complications in CD patients. Postoperative complications are not increased in UC., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)