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Background: Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited., Aim: To assess the effectiveness of dose escalation of ustekinumab., Methods: This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard-dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation., Results: A total of 142 patients (22 centres/14 countries) were included. The patients were dose-escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid-free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow-up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission., Conclusions: Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing., (© 2020 John Wiley & Sons Ltd.)

Background: Thiopurines seem to have positive effect on the pharmacokinetics of anti-tumor necrosis factor biologics. It has been suggested that a reduced dose of thiopurines is sufficient to achieve this synergism., Aims: To assess the differences of infliximab (IFX) trough levels according to the dose of concomitantly used azathioprine (AZA)., Patients & Methods: All IBD patients treated with IFX (Remicade ® ) in two IBD centres between November 2015 and April 2017 were eligible. Infliximab trough levels were assessed by ELISA (Ridascreen ® , R-Biopharm). The differences in IFX trough levels according to AZA dose were analyzed statistically., Results: In total, 125 patients were included, 42 pts (33.6%) on infliximab monotherapy, 83 pts (66.4%) using combined immune suppression. The respective median IFX levels according to AZA dose were as follows: group 1 (no concomitant AZA) 2.83 μg/ml (range 0-12); group 2 (AZA dose less than 1 mg/kg) 4.91 μg/ml (range 0.09-15.36); group 3 (AZA dose 1 < 2 mg/kg) 5.67 (range 0.16-16.97); group 4 (AZA dose above 2 mg/kg) 7.53 μg/ml (range 1.15-8.73). The differences in IFX trough levels between the respective groups according to AZA dose were statistically significant (p = 0.0159)., Conclusion: The positive effect of azathioprine on infliximab levels seems to be dependent on the dose of concomitantly used azathioprine., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

We report here an unusual case of delayed hypersensitivity reaction in a young woman with ulcerative colitis after the first administration of infliximab (IFX). The patient developed severe serum-sickness-like reaction, and her anti-IFX antibody titer increased rapidly after a single infusion of IFX. The possible reason for the delayed hypersensitivity reaction to a single IFX exposure might be the presensitization of the patient by murine antigens as she had been keeping mice and hamsters as pets for several years.

Background: The human anti-tumour necrosis factor (TNF) antibody infliximab binds to the membrane TNF and subsequently induces apoptosis of activated lamina propria T lymphocytes in patients with Crohn's disease in vitro., Aim: To test whether the ability of rapid anti-TNF-induced apoptosis in the gut predicts the efficacy of anti-TNF treatment in inflammatory bowel disease., Methods: (99m)Technetium-annexin V single-photon emission computer tomography (SPECT) was performed in 2 models of murine experimental colitis and in 14 patients with active Crohn's disease as assessed by the Crohńs Disease Activity Index (CDAI) to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. Disease activity was evaluated 2 weeks after infliximab infusion using the CDAI (definition response: drop of >100 points)., Results: Colonic uptake of (99m)Tc-annexin V significantly increased in 2,4,6-trinitrobenzene sulphonate-induced colitis as well as in transfer colitis on administration of anti-TNF antibodies compared with a control antibody as determined with dedicated animal pinhole SPECT. In addition, uptake of (99m)Tc-annexin V significantly increased in patients with active Crohn's disease responding to infliximab treatment. Colonic (99m)Tc-annexin V uptake ratio (mean (SEM)) increased from 0.24 (0.03) to 0.41(0.07) (p<0.01), 24 h after infliximab infusion (5 mg/kg). A mean increase of 98.7% in colonic uptake of (99m)Tc-annexin V could be detected in 10 of the 14 responding patients (CDAI >100 points at week 2) compared with 15.2% in non-responding patients (p = 0.03). Analysis of the mucosal biopsy specimens identified lamina propria T cells as target cells undergoing apoptosis., Conclusions: These in vivo observations support the notion that colonic uptake of (99m)Tc-annexin V correlates with clinical benefit of anti-TNF treatment and might be predictive of therapeutic success.