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Séverine Vermeire,1 François D’heygere,2 Antoine Nakad,3 Denis Franchimont,4 Fernand Fontaine,5 Edouard Louis,6 Philippe Van Hootegem,7 Olivier Dewit,8 Guy Lambrecht,9 Beatrijs Strubbe,10 Filip Baert11 1Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 2Department of Gastroenterology, AZ Groeninge, Kortrijk, Belgium; 3Department of Gastroenterology, CHWAPI, Tournai, Belgium; 4Department of Gastroenterology, Erasme Hospital, Brussels, Belgium; 5Department of Gastroenterology, CHC St Joseph, Liège, Belgium; 6Department of Gastroenterology, University Hospital CHU Sart Tilman, Liège, Belgium; 7Department of Gastroenterology, AZ St Lucas, Brugge, Belgium; 8Department of Gastroenterology, UCL St Luc, Brussels, Belgium; 9Department of Gastroenterology, AZ Damiaan, Oostende, Belgium; 10Department of Gastroenterology, OLV Hospital, Aalst, Belgium; 11Department of Gastroenterology, AZ Delta, Roeselare-Menen, Belgium Purpose: Simponi® (golimumab, MSD) is a fully human monoclonal antibody against tumor necrosis factor alpha administered subcutaneously using an autoinjector or a prefilled syringe. This study examined preference for administration of golimumab by autoinjector or prefilled syringe in patients with moderate-to-severe ulcerative colitis (UC). Patients and methods: This was a multicenter, open-label, randomized crossover trial (EudraCT no 2014-000656-29). Patients with moderate-to-severe UC were randomized 1:1 to receive 2 subcutaneous injections of 50 mg golimumab with the autoinjector followed by 2 injections of 50 mg with the prefilled syringe or the same 4 injections administered in the opposite order. Patients assessed preference, ease of use, and discomfort immediately after the injections and 2 weeks later. Results: Ninety-one patients were included (median age=42.7 years [range, 19.7–93.7]; 58% male). The autoinjector was preferred by 76.9% of patients immediately after injections and by 71.4% 2 weeks later. The autoinjector was more often considered extremely easy or easy to use (94.5%) than the prefilled syringe (73.6%). Moderate discomfort or worse was reported by more patients when using the prefilled syringe (20.9%) than when using the autoinjector (5.5%), and severe discomfort or discomfort preventing injection of future doses was reported by 8.8% for the prefilled syringe but not at all when using the autoinjector. A favorable or extremely favorable overall impression was reported by 89.0% for the autoinjector and 72.5% for the prefilled syringe. Conclusion: Most patients with moderate-to-severe UC preferred to self-administer golimumab with the autoinjector over a prefilled syringe. Keywords: autoinjector, adherence, anti-TNF, subcutaneous injection, treatment, self-injection

Background: Fatigue is common among patients with inflammatory bowel diseases (IBDs) and is associated with decreased quality of life (QoL)., Aims: Describe fatigue evolution and identify factors associated with fatigue outcomes in patients with ulcerative colitis (UC) or Crohn's disease (CD) initiating biologic treatment., Methods: Data from adult Belgian patients with UC or CD enrolled in a prospective real-world study were utilized. Fatigue and QoL were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Short Inflammatory Bowel Disease Questionnaire, respectively. Factors associated with fatigue outcomes were assessed using multivariate regression., Results: 465 patients were included: 174 with UC and 291 with CD. Average FACIT-F scores indicated improvements in fatigue after 6 months, before stabilizing. A higher probability of fatigue disappearance was associated with clinical remission and was more likely in patients with UC than CD. Patients achieving clinical remission had lower probability of fatigue. Patients with fatigue improvements experienced greater QoL improvements than patients with fatigue persistence., Conclusions: Real-world findings suggest fatigue partly improves in the first 6 months of biologic treatment. Clinical remission was associated with greater probability of fatigue disappearance and lower likelihood of fatigue persistence. Further research into factors associated with fatigue in patients with IBD is warranted., Competing Interests: Conflict of interest E.L. reports educational and research grants from AbbVie, Fresenius Kabi, Janssen, Pfizer, and Takeda; speaker fees from AbbVie, Bristol Myers Squibb, Celgene, Dr Falk, Ferring, Galapagos, Janssen, Pfizer, and Takeda; serving on advisory boards for AbbVie, Arena, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Gilead-Galapagos, Janssen, Pfizer, and Takeda; and being a consultant for AbbVie. P.B. reports research grants from AbbVie, Amgen, Celltrion, Mylan, Pfizer, and Takeda; lecture fees from AbbVie, Celltrion, Eli Lilly, Janssen, and Takeda; and consulting fees from AbbVie, Arena, Bristol Myers Squibb, Celltrion, Dr Falk, Eli Lilly, Galapagos, Janssen, Pentax, PSI-CRO, Roche, Takeda, and Tetrameros. A.C. reports consultancy fees from AbbVie, Galapagos, Janssen, and Takeda; and speaker fees from AbbVie, Celltrion, Galapagos, Janssen, and Pfizer. S.V. reports grants from AbbVie, Galapagos, Johnson & Johnson, Pfizer, and Takeda; and consulting and/or speaker fees from AbbVie, AbolerIS, AgomAb, Alimentiv, Arena, AstraZeneca, Avaxia, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CVasThera, Cytoki, Dr Falk, Eli Lilly, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, Johnson & Johnson, Materia Prima, Merck Sharp & Dohme, MiroBio, Morphic, MrMHealth, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots, and Zealand. V.S. reports receiving a research grant from Takeda. F.B. reports grant/research support from AbbVie, Amgen, Janssen, and Takeda; being a speaker for AbbVie, Celltrion, Ferring Holding SA, Janssen, Merck Sharp & Dohme, Pfizer, and Takeda; honoraria from AbbVie, Amgen, Arena, Celltrion, Ferring Holding SA, Fresenius Kabi AG, Galapagos, Janssen, Merck Sharp & Dohme, Pfizer, and Takeda. F.F. reports research grants from Takeda. A.H. and G.V.G. are employees of Takeda. J.Z. is an employee of and holds stock/stock options in Takeda. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: With point of care testing [POCT] for infliximab [IFX], ultraproactive therapeutic drug monitoring [TDM] with ad-hoc dose optimisation is possible in patients with inflammatory bowel disease [IBD]., Aim: To compare the clinical outcomes of an ultraproactive TDM algorithm of IFX based on POCT with reactive TDM in patients with IBD, in a pragmatic clinical trial., Methods: All patients with IBD and maintenance IFX treatment were included between June and August 2018 in two centres. Centre A applied an ultra-proactive TDM algorithm incorporating POCT, and centre B applied reactive TDM. Primary endpoint was failure of IFX therapy after 1 year. Secondary endpoints included sustained clinical remission and mucosal remission., Results: In total 187 patients [n = 115/72 cohort A/B] were included. Cohort A had more trough level [TL] measurements compared with cohort B [8.8 vs 1/patient/year; p <0.0001], leading to a significant higher number of dose optimisations. POCT testing was required in 27% after the first round of ultra-proactive TDM and in a mean of 6.3% (standard deviation [SD] 1.9) in the subsequent rounds. Ad-hoc extra dosing was needed in 13% of the POCT. After 1 year, no difference was seen between cohort A and cohort B in IFX failure [19% vs 10%; p = 0.08], nor in sustained clinical remission [75% vs 83%; p = 0.17]. Mucosal remission was evaluated in 71 patients [38%], and was more frequent in the reactive TDM cohort [p = 0.02]., Conclusions: Ultra-proactive TDM in patients with IBD and maintenance IFX treatment leads to equal clinical outcomes as reactive TDM after 1 year of follow-up., (© 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.)

Inflammatory bowel disease (IBD) is associated with several extra-intestinal complications, including venous thromboembolism (VTE). In patients with IBD, VTE occurs at younger age and is associated with higher recurrence and mortality rates as compared to patients without IBD. The risk appears to be higher during active disease and hospitalization. In this review we target the importance of prophylaxis and aim to describe strategies for treatment of VTE in patients with IBD. More awareness is needed, given the fact that VTE is often preventable with appropriate pharmacological prophylaxis. Algorithms are provided on which patients should be given prophylaxis and on treatment duration of VTE in patients with inflammatory bowel disease., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

An immunocompetent patient without a history of recent travel or animal exposure developed persistent abdominal bloating and cramps without diarrhoea or fever. Negative additional investigations excluded gastritis, infectious colitis, inflammatory bowel disease and neoplasia, but routine stool culture detected a Campylobacter -like organism. The isolate was obtained with use of a polycarbonate filter technique, emphasizing the importance of culture to support and validate the occurrence of emerging and new bacterial enteric pathogens. The ensuing extensive laboratory examinations proved challenging in identifying this potential pathogen. Phylogenetic marker analysis based on the 16S ribosomal RNA and rpoB gene sequences revealed that the isolate was most closely related to Arcobacter lanthieri and Arcobacter faecis . Subsequent analysis of a draft whole genome sequence assigned the isolate to A. lanthieri . We report the presence of five virulence genes, cadF , ciaB , mviN , hecA and iroE , indicating a possible pathogenic nature of this organism. This case demonstrated the importance of the use of agnostic methods for the detection of emerging pathogens in cases of enteric disease with a wide array of gastrointestinal symptoms., (© 2020 The Authors.)

Background and Aims: Vedolizumab is an IgG1 anti-α4β7 integrin antibody approved for the treatment of inflammatory bowel diseases [IBD], but without clear safety data during conception, pregnancy and nursing. Animal studies showed that mucosal vascular addressin cell adhesion molecule 1 [MAdCAM-1] is expressed by maternal vessels in the placenta and recruits α4β7-expressing cells that are considered important for maternal/fetal tolerance. Blocking this interaction by vedolizumab might affect this process. We aimed to evaluate pregnancy outcomes in vedolizumab-treated female IBD patients., Methods: We conducted a retrospective, multicentre Belgian observational study. Details on disease activity, prenatal complications, delivery and neonatal outcome were collected through a case report form., Results: Twenty-four pregnancies were reported. Five women had active disease at conception and one patient flared during pregnancy. There were 23 live births. Complications were observed in 25% of pregnancies [premature rupture of membranes, pre-eclampsia, miscarriage, elective termination and stillbirth] and in 35% of infants [prematurity, intra-uterine growth retardation, small for gestational age and congenital malformations including hip dysplasia, pulmonary valve stenosis and Hirschprung's disease]. Vedolizumab was continued throughout pregnancy in two females and stopped in the 1st and 2nd trimester in five and 16 patients, respectively. For live born children, the median [interquartile range] gestational age, weight and Apgar score 5 min after birth were 39 [37-39.6] weeks, 3270 [3080-3585] grams and 10 [9-10], respectively., Conclusions: Although several complications were observed, both in mothers and in newborns, no firm conclusions can be drawn. Awaiting prospective and controlled registries, vigilance and strict follow-up of pregnant patients treated with vedolizumab seems mandatory.

WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis, which refers to abnormal accumulation of mature neutrophils in the bone marrow. The disease is primarily caused by C-terminal truncation mutations of the chemokine receptor CXCR4, giving these CXCR4-WHIM mutants a gain of function in response to their ligand CXCL12. Considering the broad functions of CXCR4 in maintaining leukocyte homeostasis, patients are panleukopenic and display altered immune responses, likely as a consequence of impairment in the differentiation and trafficking of leukocytes. Treatment of WHIM patients currently consists of symptom relief, leading to unsatisfactory clinical responses. As an alternative and potentially more effective approach, we tested the potency and efficacy of CXCR4-specific nanobodies on inhibiting CXCR4-WHIM mutants. Nanobodies are therapeutic proteins based on the smallest functional fragments of heavy chain antibodies. They combine the advantages of small-molecule drugs and antibody-based therapeutics due to their relative small size, high stability, and high affinity. We compared the potential of monovalent and bivalent CXCR4-specific nanobodies to inhibit CXCL12-induced CXCR4-WHIM-mediated signaling with the small-molecule clinical candidate AMD3100. The CXCR4-targeting nanobodies displace CXCL12 binding and bind CXCR4-wild type and CXCR4-WHIM (R334X/S338X) mutants and with (sub-) nanomolar affinities. The nanobodies' epitope was mapped to extracellular loop 2 of CXCR4, overlapping with the binding site of CXCL12. Monovalent, and in particular bivalent, nanobodies were more potent than AMD3100 in reducing CXCL12-mediated G protein activation. In addition, CXCR4-WHIM-dependent calcium flux and wound healing of human papillomavirus-immortalized cell lines in response to CXCL12 was effectively inhibited by the nanobodies. Based on these in vitro results, we conclude that CXCR4 nanobodies hold significant potential as alternative therapeutics for CXCR4-associated diseases such as WHIM syndrome., (Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.)