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Janus kinase (JAK) inhibitors are effective anti-inflammatory agents for treatment of ulcerative colitis (UC). 1 According to drug regulatory agencies and international guidelines, JAK inhibitors should be avoided during pregnancy and lactation. 2-4 The existing evidence on safety of JAK inhibitors during pregnancy is scarce and almost exclusively limited to tofacitinib. 4-7 ., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children.Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children., (© 2024. The Author(s).)

Background: A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease may offer improved efficacy versus intravenous infliximab., Methods: Patients with refractory Crohn's disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study's primary endpoint was the treatment's persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment., Results: Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 μg/mL at W30, whereas median ATI levels significantly declined. Among ATI-negative patients at W0 ( n  = 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATI-positive patients at W0, ATI seroconversion from ATI-positive to ATI-negative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein ( P  = .0341), fecal calprotectin ( P  = .0002), and Harvey-Bradshaw index ( P = .0029) since W0., Conclusions: Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX., Competing Interests: K.C.: has consulted for Celltrion and Biogen. D.D.: has consulted for Takeda, AbbVie, Pfizer, and Janssen. M.L.: has consulted for Takeda and Pfizer. M.K.: has consulted for Pfizer. N.M.: has consulted for Takeda and Janssen. V.H.: has consulted for Biogen and Janssen. K.M.: has consulted for Takeda and Janssen. K.K.: has consulted for Abbott. M.K.: has consulted for Takeda and Janssen. J.J.: none. K.K.: none. G.V.: none. S.P.: none. M.L.: provided consultations and received fees for lectures by Celltrion, Abbvie, Janssen, Takeda, and Ferring., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers., Competing Interests: Declaration of interests JB reports personal fees from AbbVie, Celgene, Pfizer, Samsung Bioepis, Pharmacosmos, Ferring, and Galapagos; grants and personal fees from Janssen, MSD, Takeda, Tillots Pharma, and Bristol Myers Squibb; and grants from Novo Nordisk. MZ has received support for attending a meeting from Takeda. PDC has received grants or contracts from Janssen, Takeda, Ferring, Shire, AbbVie, Celltrion, and Baxter. PDC has been a speaker, consultant, and advisory board member for AbbVie, Janssen, Takeda, Celltrion, Ferring, Shire, and Baxter; received support for travel or attending meetings or both from Ferring, Shire, Janssen, AbbVie, Takeda, Celltrion, and Baxter; and has been a member of the Australia and New Zealand IBD Research Consortium. SV has received research grants from Pfizer, Galapagos, AbbVie, Johnson & Johnson, and Takeda; consulting fees from AbbVie, AbolerIS Pharma, Agomab, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech–Roche, Gilead, GSK, Hospira, Imidomics, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma, Zealand Pharma; speaker fees from Alimentiv, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Ferring, Galapagos, Genentech–Roche, Gilead, GSK, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, Pfizer, Takeda, and Tillots Pharma. CNB has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, JAMP Pharma, Roche Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada; is a consultant for Mylan Pharmaceuticals and Takeda; and educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. CNB is on the speaker's panel for AbbVie Canada, Janssen Canada, Medtronic Canada, and Takeda Canada; and has received research funding from AbbVie Canada and Pfizer Canada. GGK has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, Amgen, Sandoz, Pendopharm, and Takeda. He has received research support from Ferring. He shares ownership of a patent: treatment of inflammatory disorders, autoimmune disease, and pbc (WO2019046959A1. PCT/CA2018/051098) since Sept 7, 2018. DD has received lecture or consultancy fees from Takeda, Janssen, and Pfizer, and support for travel or attending meetings or both from Janssen and Takeda. MW has received grants or contracts from Mitsubishi Tanabe Pharma, Takeda, Zeria Pharmaceutical, Nippon Kayaku, Mochida Pharmaceutical, Kyorin Pharmaceutical, AbbVie, EA Pharma, Kissei Pharmaceutical, and Alfresa Pharma; consulting fees from AbbVie, EA Pharma, Eli Lilly Japan, Gilead Sciences, Nippon Boehringer Ingelheim, and Takeda Pharmaceutical; and honoraria from EA Pharma, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Zeria Pharmaceutical, Pfizer Japan, Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Gilead Sciences, Janssen Pharmaceutical, Celltrion Healthcare, JIMRO, Eli Lilly Japan, and Mochida Pharmaceutical. LT has received grants or contracts from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, and Amgen; consulting fees from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, Amgen, Fresnius Kabi, and Viatris; and honoraria for lectures from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, Amgen, and Organon. KP is an employee of Genentech–Roche and a shareholder of the Roche Group. KHK has served as speaker, consultant, and advisory member for or has received research funding from AbbVie, Amgen, Enorasis, Epsilon Health, Dr Falk Pharma, Faran Ferring, Genesis, Grifols, Janssen, Koper, MSD, Mylan, Shire, Takeda, and Vianex. MLH has received investigator-initiated research grants from Tillotts, Ferring, Takeda, and Pfizer; advisory board honoraria from Takeda and AbbVie; and speaking fees from Takeda, AbbVie, Tillotts, Ferring, Galapagos, Janssen, and MSD. ZK has served as speaker for AbbVie, Takeda, Janssen, Freseinus, and Oktal Pharma/Celltrion. MC has served as a speaker, as a consultant, or has received research or education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Biogen, Gilead, and Eli Lilly. EVL has received grants or contracts from AbbVie, Bristol Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Takeda, Theravance, and UCB; consulting fees from AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Celgene, Fresenius Kabi, Genentech, Gilead, Gossamer Bio, Janssen, Iterative Scopes, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Surrozen, Takeda, and UCB; reports the following patents: USA 11 249 084 (issued), USA 10 041 948 (issued), and USA 17 668 915 (pending); has participated on a data safety monitoring board or advisory board for Eli Lilly and Morphic; owns stock in Exact Sciences; and is a board member of Crohn's & Colitis Foundation, Minnesota-Dakotas Chapter. PLL has been a speaker or advisory board member, or both, for AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genentech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Takeda, Tillots, and Viatris, and has received unrestricted research grants from AbbVie, Gilead, Takeda, and Pfizer. JPG has served as a speaker, consultant, and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers Squibb, Gilead/Galapagos, Eli Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, and Vifor Pharma. WB has received research grants from Vifor Pharma and B Braun Medical; consulting fees from Takeda and B Braun Medical; speaker fees from Medtronic, Takeda, B Braun Medical, and Johnson & Johnson; and is a stock owner of Semiflex Company. RBG has received grants or contracts from AbbVie and Janssen; consulting fees from AbbVie; and honoraria for lectures from AbbVie and Cornerstone Health. MDK has received grants or contracts from Pfizer, Takeda, Janssen, AbbVie, Eli Lilly, Genentech, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, and Arenapharm; consulting fees from Takeda and Pfizer; speaker fees from AbbVie; has participated on data safety monitoring board or advisory board for Eli Lilly; and owns stock in Johnson & Johnson. MJP has received grants or contracts from Takeda, Janssen, Galapagos, Tramedico, MSD, Takeda, Janssen, and Bristol Myers Squibb; honoraria for lectures from Bristol Myers Squibb, Janssen, AbbVie, and Galapagos; consulting fees from Janssen and Gilead; and has a leadership or fiduciary role in the MyCoach foundation. JMA has served as speaker, consultant, and advisory member for AbbVie, Allergan, Anatara, Atmo Capsule, Bayer, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Ferring Fresenius Kabi, Gilead, Hospira, Immuninc, ImmunsanT, Janssen, MSD, Nestle, Novartis, Pfizer, Sandoz, Shire, Takeda, and Vifor; has participated on a data safety monitoring board or advisory board for Janssen; has received research grants from the Royal Adelaide Hospital research fund, The Hospital Research Fund 2020–22, and The Helmsley Trust 2020–23. SCN has received grants or contracts from AbbVie, Ferring, and Olympus and Janssen; consulting fees from AbbVie, Pfizer, Ferring, and Janssen; honoraria for lectures from AbbVie, Ferring, Janssen, Menarini, Takeda, Tillotts and Pfizer; has participated on a data safety monitoring board or advisory board for AbbVie, Pfizer, Ferring, and Janssen; is a shareholder of GeniBiome; and is a director of the Microbiota I-Center, Hong Kong. HOM has received research grants from Takeda and Biogen, consulting fees from Takeda, and speaking fees from Pfizer and Biogen. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: Evidence on the safety of newer biologics during pregnancy is limited. We aimed to assess the safety of ustekinumab and vedolizumab treatment during gestation on pregnancy and infant outcome. Furthermore, we evaluated the placental transfer of these agents., Methods: We performed a prospective, multicentre, observational study in consecutive women with inflammatory bowel disease exposed to ustekinumab or vedolizumab 2 months prior to conception or during pregnancy. Pregnancy, neonatal, and infant outcomes were evaluated and compared with the anti-tumour necrosis factor [TNF]-exposed control group. Drug levels were assessed in maternal and cord blood at delivery., Results: We included 54 and 39 pregnancies exposed to ustekinumab and vedolizumab, respectively. In the ustekinumab group, 43 [79.9%] resulted in live births, and 11 [20.4%] led to spontaneous abortion. Thirty-five [89.7%] pregnancies on vedolizumab ended in a live birth, two [5.1%] in spontaneous, and two [5.1%] in therapeutic abortion. No significant difference in pregnancy outcome between either the vedolizumab or the ustekinumab group and controls was observed [p >0.05]. Similarly, there was no negative safety signal in the postnatal outcome of exposed children regarding growth, psychomotor development, and risk of allergy/atopy or infectious complications. The median infant-to-maternal ratio of ustekinumab levels was 1.67 and it was 0.59 in vedolizumab., Conclusions: Use of ustekinumab and vedolizumab in pregnancy seems to be safe, with favuorable pregnancy and postnatal infant outcomes. Placental transfer differed between these two drugs, with ustekinumab having similar and vedolizumab having inverse infant-to-maternal ratio of drug levels compared with anti-TNF preparations., (© 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: Knowledge on the immunogenicity of anti-SARS-CoV-2 vaccines in inflammatory bowel disease [IBD] patients is limited. Therefore, SARS-CoV-2-specific T-cell responses and antibodies were analysed in 60 IBD vaccine recipients and 30 controls., Methods: SARS-CoV-2 IgG antibodies against the viral spike protein were measured at baseline and at 8 and 26 weeks after the second vaccine dose. SARS-CoV-2 IgG antibodies against the nucleocapsid antigens were measured at week 26. A SARS-CoV-2 interferon-gamma released assay [IGRA] was performed in all vaccinees at week 26., Results: At weeks 0 and 8, no differences were found in anti-spike antibodies between cohorts. At week 26, the decrease in antibody levels was more significant in the IBD cohort compared to the healthy cohort, and anti-nucleocapsid antibodies were not detected in either group. At week 26, 16 of 90 [18%] vaccinated individuals had a negative IGRA test result, seven of 90 [8%] were borderline and 67 [74%] had a positive IGRA result; 22 of the 23 individuals with negative or borderline IGRA results belonged to the IBD cohort. However, the overall functional ability of T-lymphocytes to produce interferon-gamma after the unspecific mitogen stimulation was lower in IBD patients. In vaccinated individuals with low or borderline IGRA, treatment with tumour necrosis factor-alpha inhibitors was the most frequent. In individuals with a significant drop in anti-spike antibody levels, plasmatic interferon-gamma concentrations after the specific SARS-CoV-2 stimulation were also insufficient., Conclusions: Simple humoral and cellular post-vaccination monitoring is advisable in IBD patients so that repeated vaccine doses may be scheduled., (© 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/aims: Originator-adalimumab, an established treatment for patients with Crohn's disease (CD), showed no difference in efficacy or adverse events versus adalimumab biosimilar SB5 (SB5-adalimumab) over 10 weeks (W) of treatment. To understand the long-term effectiveness of SB5-adalimumab in CD, patients switched from originator-adalimumab to SB5-adalimumab were compared with patients remaining on originator-adalimumab over 104 W., Methods: Data on patients aged ≥18 years, diagnosed with CD and treated at ISCARE, were collected prospectively from July 2018 to January 2021. Primary outcome: clinical disease activity at W52, measured by Harvey-Bradshaw index (HBI). Secondary outcomes: C-reactive protein (CRP), faecal calprotectin (FC) and adalimumab concentrations at W10, 26, 52 and 104, and treatment persistence. To ensure comparable cohorts, patients were propensity score (PS)-matched for age, gender and disease activity., Results: After matching, 54 patients remained per cohort. At W52, mean (SD) HBI score was 3.2 (2.5) for originator-adalimumab and 4.0 [3.6] for SB5-adalimumab (difference [95% CI] -0.78 [-2.8, 1.3]; n = 18/cohort); no clinically meaningful differences in CRP, FC or drug concentrations were noted. Kaplan-Meier's estimates (95% CI) of remaining on treatment were originator-adalimumab: 0.870 (0.785-0.965) versus SB5-adalimumab: 0.648 (0.533-0.789) at W52 and significantly lower for SB5-adalimumab versus originator-adalimumab ( p < .001) over 104 W. Local skin reaction events/pain was the main reason for treatment discontinuation in the SB5-adalimumab cohort ( n  = 20/54 [37%])., Conclusions: These long-term results of CD patients receiving originator-adalimumab or following nonmedical switch to SB5-adalimumab show similar therapeutic effects on clinical disease activity, biological parameters and pharmacokinetic profile in both cohorts from 52 to 104 W. A separation in persistence was observed beyond W26, mainly due to differences in local reactions at the injection site.

Background & Aims: The Lémann Index is a tool measuring cumulative structural bowel damage in Crohn's disease (CD). We reported on its validation and updating., Methods: This was an international, multicenter, prospective, cross-sectional observational study. At each center, 10 inclusions, stratified by CD duration and location, were planned. For each patient, the digestive tract was divided into 4 organs, upper tract, small bowel, colon/rectum, anus, and subsequently into segments, explored systematically by magnetic resonance imaging and by endoscopies in relation to disease location. For each segment, investigators retrieved information on previous surgical procedures, identified predefined strictures and penetrating lesions of maximal severity (grades 1-3) at each organ investigational method (gastroenterologist and radiologist for magnetic resonance imaging), provided segmental damage evaluation ranging from 0.0 to 10.0 (complete resection). Organ resection-free cumulative damage evaluation was then calculated from the sum of segmental damages. Then investigators provided a 0-10 global damage evaluation from the 4-organ standardized cumulative damage evaluations. Simple linear regressions of investigator damage evaluations on their corresponding Lémann Index were studied, as well as calibration plots. Finally, updated Lémann Index was derived through multiple linear mixed models applied to combined development and validation samples., Results: In 15 centers, 134 patients were included. Correlation coefficients between investigator damage evaluations and Lémann Indexes were >0.80. When analyzing data in 272 patients from both samples and 27 centers, the unbiased correlation estimates were 0.89, 0,97, 0,94, 0.81, and 0.91 for the 4 organs and globally, and stable when applied to one sample or the other., Conclusions: The updated Lémann Index is a well-established index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials., (Copyright © 2021. Published by Elsevier Inc.)

Background: Vedolizumab demonstrated different placental pharmacokinetics than other immunoglobulin G1 antibodies, leading to lower drug levels in cord blood in contrast to maternal blood at the time of delivery. The placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor agents. Current evidence on the placental pharmacokinetics of vedolizumab and ustekinumab is limited. We aimed to assess the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease., Methods: Consecutive women from a prospective observational study who were exposed to ustekinumab or vedolizumab within 2 months prior to conception or during pregnancy were included. Ustekinumab and vedolizumab levels were measured in maternal and cord blood at the time of delivery., Results: Drug levels were available in 31 infant-mother pairs (15 exposed to ustekinumab and 16 to vedolizumab). The median maternal and newborn ustekinumab levels were 5.3 mg/l and 10.3 mg/l, respectively (the median infant-to-maternal ratio was 1.7), while the median maternal and cord vedolizumab levels were 7.3 mg/l and 4.5 mg/l (the median infant-to-maternal ratio was 0.66). The ustekinumab levels in cord blood positively correlated with the maternal levels at delivery (ρ = 0.751, p  = 0.001). However, no correlation with the timing of the last drug administration was found. In contrast, the vedolizumab levels in cord blood demonstrated significant positive correlation with the maternal levels (ρ = 0.831, p  < 0.001) along with the gestational week of the last infusion (ρ = 0.736, p  = 0.001)., Conclusion: Vedolizumab demonstrated different placental pharmacokinetics, leading to lower drug levels in cord blood compared to maternal blood at delivery; in contrast, the placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor (TNF) agents., Competing Interests: Conflict of interest statement: Katarina Mitrova: Lectures/congress fees/consultancy (outside the submitted work): Abbvie, Takeda Barbora Pipek: Pfizer Martin Bortlik: Abbvie, Jansen, Pfizer, Takeda, Biogen, Egis Pavel Drastich: Takeda Milan Lukas: Janssen, MSD, Pfizer, Takeda, Egis Dana Duricova: Lectures/congress fees/consultancy (outside the submitted work): Takeda, Jansen, Pfizer Ludek Bouchner, Jan Brezina, Tomas Douda, Tomas Drasar, Premysl Falt, Pavel Klvana, Vaclav Leksa, Ales Novotny, Pavel Svoboda, Jan Skorpik, Jan Ulbrych, Marek Veinfurt, Blanka Zborilova: No disclosure, (© The Author(s), 2021.)

Background: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice., Aims: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease., Methods: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists., Results: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%))., Conclusion: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

Background and Aims: Patients' perspectives after switching from originator to biosimilar adalimumab have yet to be assessed. We evaluated the efficacy of switching from the originator adalimumab to a biosimilar compound [SB5] in patients with inflammatory bowel disease [IBD]., Methods: Data on IBD patients who were switched from the originator to biosimilar adalimumab [SB5] at IBD Center ISCARE were analysed. Disease activity was assessed using standard clinical indices (Harvey-Bradshaw index [HBI] for Crohn's disease [CD] and partial Mayo score for ulcerative colitis [UC]), and laboratory parameters (C-reactive protein [CRP] and faecal calprotectin [FC]). Trough levels and anti-drug antibodies were measured. Patients were evaluated 10 weeks [W10] after the switch, and results were compared with the control group of patients on originator compound., Results: A total of 93 patients switched to biosimilar adalimumab were included [CD 86%] and were matched to 93 controls for age, gender, diagnosis, and disease activity. There was no difference in the disease activity in either SWITCH or ORIGINATOR cohorts between Weeks 0 and 10. Similarly, no difference was found between cohorts at both prespecified time points. Moreover, no significant differences in CRP or FC concentrations were seen between W0 and W10 either in the SWITCH, or in the ORIGINATOR cohort [p >0.05]. Adalimumab serum trough levels remained stable after the switch. No new safety signals were detected., Conclusions: Our study confirmed that switching IBD patients from the originator adalimumab to a biosimilar compound [SB5] does not affect treatment efficacy., (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.)

Background: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up., Methods: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery., Findings: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001)., Interpretation: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease., Funding: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Data on long-term natural history of microscopic colitis (MC), including collagenous (CC) and lymphocytic colitis (LC), are lacking., Methods: All new cases of MC diagnosed in the Somme area, France, between January 1, 2005, and December 31, 2007, were prospectively included. Colonic biopsies from all patients were reviewed by a group of 4 gastrointestinal pathologist experts to assess the diagnosis of CC or LC. Demographic and clinical data were retrospectively collected from diagnosis to February 28, 2017., Results: One hundred thirty cases of MC, 87 CC and 43 LC, were included (median age at diagnosis: 70 [interquartile range, 61-77] and 48 [IQR, 40-61] years, respectively). The median follow-up was 9.6 years (7.6; 10.6). By the end of the follow-up, 37 patients (28%) relapsed after a median time of 3.9 years (1.2; 5.0) since diagnosis, without significant difference between CC and LC (30% vs 26%; P = 0.47). Twenty patients (15%) were hospitalized for a disease flare, and 32 patients (25%) presented another autoimmune disease. Budesonide was the most widely used treatment (n = 74, 59%), followed by 5-aminosalicylic acid (n = 31, 25%). The median duration of budesonide treatment was 92 days (70; 168), and no adverse event to budesonide was reported. Sixteen patients (22%) developed steroid dependency and 4 (5%) were corticoresistant. No difference in the risk of digestive and extradigestive cancer was observed compared with the general population. None of the death (n = 25) observed during the follow-up were linked to MC. In multivariate analysis, age at diagnosis (HR, 1.03; 95% confidence interval, 1.00-1.06; P = 0.02) and budesonide exposure (HR, 2.50; 95% confidence interval, 1.11-5.55; P = 0.03) were significantly associated with relapse., Discussion: This population-based study showed that after diagnosis, two-third of the patients with MC observed long-term clinical remission. Age at diagnosis and budesonide exposure were associated with a risk of relapse.

Background and Aim: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years., Methods: The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period., Results: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU., Conclusions: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Evidence of the impact of in utero exposure to anti-tumor necrosis factor (TNF)-alpha on long-term childhood development is limited. The aim was to assess the impact of in utero exposure to anti-TNF-alpha due to mothers' inflammatory bowel disease (IBD) on long-term postnatal development of exposed children., Methods: We included consecutive children (≥12 months of age) born to mothers with IBD (2007-2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic. A control group was comprised of unexposed children of non-IBD mothers undergoing mandatory check-ups at general pediatricians' offices. Data on perinatal period, psychomotor development, vaccination, infections, antibiotics, and allergy were collected by treating pediatricians using a predefined questionnaire., Results: Seventy-two exposed and 69 unexposed children were included (median age, 35 and 50 months, respectively). Exposed children had growth and psychomotor development similar to controls. There was no significant difference in infectious complications within the first year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between exposed infants and controls (P = 0.32). Concomitant immunosuppressants during pregnancy and anti-TNF-alpha levels in cord blood were not associated with elevated infection rate within the first year of life (P > 0.05). Over 95% of exposed children had adequate serologic response to vaccination, except for haemophilus and mumps vaccines. Clinically manifested allergy was similar between the groups (P = 0.98)., Conclusions: Anti-TNF-alpha exposure in utero does not seem to have a negative impact on postnatal development of children with regard to infectious complications, allergy, growth, or psychomotor development when compared with unexposed children of non-IBD women., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD)., Design: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis., Results: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5)., Conclusion: Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation., Competing Interests: Competing interests: JB: consulting fees from Celgene, Janssen-Cilag, AbbVie A/S and Ferring and lecture fees from Abbvie A/S, Pfizer, MSD and Takeda Pharma A/S. VA: consultancy for Janssen and MSD. RS: consulting fees and/or lecture fees from AbbVie, MSD, Takeda, Janssen-Cilag. RD’I: consulting fees from Abbvie, Biocure and lecture fees from Takeda and Mundipharma. MF: speaker/lecture fees for Abbvie, Ferring, MSD, Takeda, Boehringer and Hospira. CG-R: lecture fees from Takeda, MSD, Ferring and Tillots. CE: lecture fees from Takeda. JH: research grants from Janssen, MSD and Takeda and lecture and/or consultancy fees from Abbvie, Cellgene, Ferring, Hospira, Janssen, Medivir, MSD, Pfizer, Vifor Pharma, Takeda and Tillotts Pharma. EL: lecture or consultancy fees from MSD, Abbvie and Ferring Pharmaceuticals. DD: lecture or consultancy fees from AbbVie, Takeda and Janssen. NA: lecture fees from MSD and Jansen. VH: personal fees, non-financial support and other from MSD, AbbVie, Ferring, Faes Farma, Shire, Falk Pharma, Tillots, Otsuka, Hospira Biologicals, Takeda, Jansen and Kernpharma Biologics. AF: personal fees and non-financial support from MSD, AbbVie, Shire and Tillots. SČ-Č: lecture fees from Takeda, MSD, Abbvie., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort., Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis., Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8]., Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.

Background: Extraintestinal manifestations (EIM) have been associated with more severe course of inflammatory bowel disease. The aim was to study the frequency of EIM in pediatric- and elderly-onset Crohn's disease (CD) and the factors associated with EIM and their impact on long-term disease outcome., Methods: Pediatric- (age at diagnosis younger than 17 years) and elderly-onset CD patients (age at diagnosis 60 years or older) from a prospective population-based registry (EPIMAD) were recruited. Data on EIM and clinical factors at diagnosis and at maximal follow-up were collected., Results: We included 535 pediatric- and 370 elderly-onset patients (median age 14.5 and 69.9 years; median follow-up 11.1 and 5.9 years). Extraintestinal manifestations presented in 23.5% of childhood-onset and 4.9% of elderly-onset individuals at diagnosis, while in 29.8% and 5.9% of patients, EIM developed newly during the follow-up (hazard ration [HR] 4.4, 95% CI, 2.7-7.0, P < 0.001). The most frequently involved organ in both age cohorts, either at diagnosis or during disease course, were joints (pediatric: 11.2% and 22.6%; elderly: 3.2% and 3.5%, respectively) followed by skin (pediatric: 15.9% and 13.6%; elderly: 2.7% and 2.7%, respectively). Extraintestinal manifestations at diagnosis were associated with increased risk for corticosteroids (HR 1.42, 95% CI, 1.14-1.78 and HR 3.38, 95% CI, 1.88-6.08) and immunosuppressive therapy (HR 1.30, 95% CI, 1.02-1.65 and HR 4.24, 95% CI, 1.91-9.42), in both age populations., Conclusions: Extraintestinal manifestations occurred at lower frequency in elderly-onset compared with pediatric-onset patients. In both age populations, presence of EIM at diagnosis independently increased the need for corticosteroid and immunosuppressive treatment.

Background: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing., Materials and Methods: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores., Results: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053)., Conclusion: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.

Background: CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX), has previously been confirmed to be efficacious in inducing mucosal healing in ulcerative colitis (UC) patients. The aim of this study was to evaluate the efficacy of CT-P13 therapy in maintaining mucosal healing in UC., Methods: CT-P13 trough levels, antibody positivity, serum inflammatory markers as CRP level, fecal calprotectin at weeks 14 and 54, concomitant steroid and azathioprine therapy at the time of induction therapy and at weeks 14 and 54, previous use of anti TNF drug and the need of dose intensification as possible predictive factors for mucosal healing at week 54 were evaluated in this prospective study., Results: 61 patients had already completed the 54-week treatment period. Mucosal healing was shown in 65.5 % and 62.1 %, complete mucosal healing was present in 31% and 38 % at week 14 and 54, respectively. The median values of CRP, leukocytes, thrombocytes, and albumin showed significant difference between baseline and week 54. Serum antibody positivity was proved in 6.5 % and 19.7 % of cases at week 14 and 54, respectively., Conclusion: Our study confirmed the long-term efficacy of CT-P13 therapy on mucosal healing in UC.

Background: Recent population-based study of elderly-onset Crohn's disease patients reported age-related differences in disease phenotype and outcome., Aims: The aim was to assess the impact of age at diagnosis on natural history of elderly-onset ulcerative colitis patients with emphasis on disease presentation, phenotype and treatment., Methods: Elderly-onset patients with ulcerative colitis (≥60 years at diagnosis) registered in a French population-based Registry EPIMAD (1988-2006) were included. Demographic and clinical data at diagnosis and at maximal follow-up were collected using predefined questionnaire., Results: Four-hundred and sixty-five elderly-onset ulcerative colitis patients were included (median follow-up 6.2 years); 276 (59%) were <70 and 189 (41%) ≥70 years at diagnosis. Patients aged <70 years presented with more rectal bleeding (86% vs. 79%, p = .06) and abdominal pain (44% vs. 34%, p = .04) while those ≥70 years had higher rate of left-sided colitis (62% vs. 49%; p = .02). Cumulative exposure to 5-ASA, corticosteroids and immunosuppressants was similar between the groups as well as surgery rate. However, patients <70 years were significantly more steroid-resistant than older individuals (12% vs. 3%, p < .05) while no significant difference in steroid-dependency was observed., Conclusion: Patients with elderly-onset ulcerative colitis differed in presentation, disease phenotype and response to medication with respect to age at diagnosis., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Data on extra-intestinal manifestations [EIM] and their impact on the disease course of ulcerative colitis [UC] in population-based cohorts are scarce, particularly in paediatric- and elderly-onset UC patients. The aims of this population-based study were to assess: 1] the occurrence of EIM in paediatric- and elderly-onset UC; 2] the factors associated with EIM; and 3] their impact on long-term disease outcome., Methods: Paediatric-onset [< 17 years at diagnosis] and elderly-onset UC patients [> 60 years at diagnosis] from a French prospective population-based registry [EPIMAD] were included. Data on EIM and other clinical factors at diagnosis and at maximal follow-up were collected., Results: In all, 158 paediatric- and 470 elderly-onset patients were included [median age at diagnosis 14.5 and 68.8 years, median follow-up 11.2 and 6.2 years, respectively]. EIM occurred in 8.9% of childhood- and 3% of elderly-onset patients at diagnosis and in 16.7% and 2.2% of individuals during follow-up [p < 0.01], respectively. The most frequent EIM was joint involvement [15.8% of paediatric onset and 2.6% of elderly-onset]. Presence of EIM at diagnosis was associated with more severe disease course [need for immunosuppressants or biologic therapy or colectomy] in both paediatric- and elderly-onset UC (hazard ratio [HR] = 2.0, 95% confidence interval [CI]: 1.0-4.2; and HR = 2.8, 0.9-7.9, respectively). Extensive colitis was another independent risk factor in both age groups., Conclusions: Elderly-onset UC patients had lower risk of EIM either at diagnosis or during follow-up than paediatric-onset individuals. EIM at diagnosis predicted more severe disease outcome, including need for immunosuppressive or biologic therapy or surgery, in both paediatric- and elderly-onset UC., (Copyright © 2017 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: Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort., Methods: Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria., Results: A total of 1871 patients (Crohn's disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed., Conclusions: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: Safety data of the 'real life' use of an infliximab biosimilar, CT-P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess the frequency and characteristics of infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD centres., Methods: Clinical and safety data was registered at fixed appointments. Trough levels and anti-drug antibody (ADA) concentration were measured by ELISA. Association between demographic, clinical, laboratory parameters and infusion reaction rates were evaluated statistically., Results: Three hundred and eighty-four IBD patients were included. Twenty-eight Hungarian IBD patients (9.6%) developed infusion reaction during the treatment, 64.3% of them was previously exposed to anti TNF therapy. No infusion reaction occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients who developed infusion reaction and was switched to adalimumab in 12 patients. However in 39.3% of patients developing infusion reaction CT-P13 therapy was continued with the use of premedication. Cumulative ADA positivity rates were 8.7%, 19.3%, and 28.0% at weeks 0, 14, and 30. Previous anti-TNF-alpha exposure (30% vs. 3.1%, p < 0.001, OR 6.3 (2.7-14.6)) and ADA positivity (32.6% vs. 4.1%, p < 0.001, OR 19(5-73)) during the induction therapy were predictive factors for infusion reactions., Conclusions: Patients with previous exposure to anti-TNF-alpha and ADA positivity during the induction therapy were more likely to develop infusion reactions.

The incidence of Crohn's disease (CD) has been reported to increase. The aim of this review is to perform a comprehensive literature search of population-based studies focused on the natural history of paediatric-onset CD. A literature search of English and non-English language publications listed in the electronic database of MEDLINE (source PUBMED) and EMBASE from 1935 to 2016 was performed. Population-based studies or national cohorts reporting data on the short-term or long-term disease course of paediatric CD were included. Forty-nine paediatric and 15 nonpaediatric studies on CD have been identified. Up to one-third of children with inflammatory behaviour developed bowel complications more than 5 years after diagnosis. From 48 to 88% of children have experienced at least one corticosteroid course irrespective of the period of diagnosis and up to one-third became steroid dependent. Immunosuppressive preparations were used earlier and more frequently in newer than older cohorts (68 vs. 32% at 5 years) and more than one-third of children have received biological treatment early in the disease course. A decline in the surgery rate might be observed in more recent compared with older unselected populations. The relative risk of cancer in childhood-onset CD as well as the risk of death seem to have increased. Childhood-onset CD seems to be an aggressive phenotype of the disease. Compared with older cohorts, a trend towards decreasing surgical rate can be observed in newer cohorts paralleled by an increase in immunomodulator use and biologicals. Nevertheless, the causative role has yet to be investigated.

Background: The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse., Methods: Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort., Results: Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts., Conclusion: Switching of IBD patients from original to biosimilar IFX is effective and safe., (© 2017 S. Karger AG, Basel.)

Background: Population-based studies represent the whole spectrum of patient population and should represent the mainstay when evaluating patients' prognosis. A high number of CD patients need surgical intervention during the disease course. The disease course of inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn's disease (CD), is quite varied and still quite unpredictable. Key Messages: According to earlier studies, up to 60% of patients undergo at least one operation after 10 years of CD duration. Newer cohorts report lower cumulative probability of surgery of approximately 40% after 10 years. The colectomy rate in UC is approximately 10% after 10 years from diagnosis with a geographic difference. Similarly to CD, the colectomy rate seems to decrease over time. There is some evidence that the increasing use of immunosuppressive and/or biological therapy might have been responsible for this favourable trend. However, other factors may have an impact on decreasing surgical trend over time. The relative risk (RR) of colorectal cancer (CRC) in UC is approximately doubled compared to background population. However, the absolute risk in general is relatively low between 1.1 and 5.3% after 20 years of disease duration. Furthermore, a decreasing trend in the incidence of CRC has been reported in recent studies. Importantly, several factors such as disease extent, activity, age at UC onset, and so on may increase/modify an individual risk. Similar to UC, CD patients have approximately 2 times higher RR of cancer compared to background population. The risk is higher for colon than for rectum cancer and present only in CD patients with colonic involvement., Conclusions: The surgery rate in CD has decreased over the time period. The evidence on colectomy rate in UC is less conclusive. The RR of CRC in UC and CD is approximately doubled compared to that of the background population, but it seems to be decreasing in more recent cohorts., (© 2017 S. Karger AG, Basel.)

Introduction: CT-P13 is the first biosimilar to infliximab that has been approved for the same indications as its originator infliximab. No data are available on the effect of infliximab biosimilar on mucosal healing. The aim of this study was to evaluate the efficacy of CT-P13 induction therapy on mucosal healing in patients with ulcerative colitis [UC]., Patients and Methods: UC patients, who received CT-P13 therapy from its local introduction at three Hungarian and one Czech inflammatory bowel disease centres, were prospectively enrolled. Sigmoidoscopy was performed after the end of the induction therapy at week 14. Mucosal healing was defined as Mayo endoscopic subscore 0 or 1. Complete mucosal healing was defined as Mayo endoscopic subscore 0. Trough level of CT-P13 was measured at week 14., Results: Sixty-three UC patients who underwent CT-P13 induction therapy were enrolled in the study. Indication for the therapy was acute, severe flare up and chronic, refractory activity in 24 and 39 patients, respectively. Cumulative clinical response and steroid-free remission at week 14 were achieved in 82.5% and 47.6% of the patients, respectively. Sigmoidoscopy revealed steroid-free mucosal healing in 47.6% of the patients, and complete mucosal healing was present in 27%. Mayo endoscopic subscore decreased significantly at week 14 compared to baseline. Trough levels of infliximab correlated with mucosal healing., Conclusion: This is, to our knowledge, the first study examining the efficacy of CT-P13 induction therapy on mucosal healing in UC. The results indicate that mucosal healing is achieved in two-thirds of UC patients by the end of the induction treatment with CT-P13., (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: A better knowledge of the natural history of disabling chronic diseases is essential to improve patient management, evaluate the impact of treatment strategies and provide predictors for disabling disease and comprehensive information for patients., Aim: To summarise our current knowledge issued from population-based studies of the natural history of ulcerative colitis (UC) in children., Methods: We searched MEDLINE (source PubMed) and international conference abstracts, and included all population-based studies that evaluated long-term outcome of paediatric-onset (<17 years at diagnosis) UC., Results: A total of 26 population-based studies were considered in this review from the total of 61 articles or abstracts screened. Most patients presented disease extension and about two-thirds of patients had pancolitis at the end of follow-up. One-half of patients experienced extra-intestinal manifestations and primary sclerosing cholangitis was observed in 5-10% of patients. Overall, patients did not appear to have any significant growth retardation or delayed puberty. About two-thirds of patients required corticosteroid therapy and up to 25% were steroid dependent. An increased use of thiopurines was observed and the most recent data indicate that up to one-half of patients were exposed to thiopurines and 10-30% were exposed to anti-tumour necrosis factor. One-half of patients required hospitalisations and 20% of patients required colectomy after a follow-up of 10 years., Conclusions: Paediatric-onset UC is characterised by a high rate of disease extension. About 20% of patients had been operated at 10-year follow-up. New population-based studies are needed to evaluate the impact of new treatment strategies comprising immunosuppressants and biologics., (© 2015 John Wiley & Sons Ltd.)