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Background: It is unknown which maintenance therapy is the most effective option for patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous steroids., Methods: We conducted a multicentre, parallel-group, open-label randomised controlled trial among 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids. Eligible patients were randomly assigned to receive infliximab (IFX) and azathioprine (AZA) with a 7-day steroid tapering scheme (IFX+AZA arm) or AZA and conventional standardised steroid tapering regimen (AZA arm). The primary composite endpoint was treatment failure at week 52, defined as the absence of steroid-free clinical remission, the absence of endoscopic response, the use of a prohibited treatment for relapse, severe adverse event leading to treatment interruption, colectomy or death. Multiple imputation for missing data was performed., Findings: Among the 64 patients randomised (Lichtiger score 13.5±2.0; median age of 34.5 (P25-P75 26.3-50.3) years, median C reactive protein of 29.0 (12.8-96.8) mg/L at baseline): 32 were assigned to the IFX+AZA arm and 32 to the AZA arm. In the ITT population, treatment failure at week 52 was observed in 22/27 (81.5%) in the AZA arm and 16/30 (53.3%) in the IFX+AZA arm (risk ratio 3.85, 95% CI (1.15 to 12.88), p=0.03). 29 adverse events were severe, including 13 disease exacerbations, 6 severe infections without any difference between both arms., Interpretation: Combination therapy with IFX+AZA was more effective at 1 year than AZA alone to avoid treatment failure in patients with ASUC responding to intravenous steroids., Trial Registration Number: NCT02425852., Competing Interests: Competing interests: AA received consulting fees from Abbvie, Pfizer, Takeda, Tillotts Pharma, Janssen and Sandoz as well as lecture fees and travel accommodations from Abbvie, Janssen, Pfizer, Takeda, Biogen, Fresenius Kabi, Amgen and Celltrion. PS reports consulting fees from Pfizer, Astellas, Janssen, Fresenius Kabi, Takeda, Abbvie, Merck-MSD, Pilège, Lilly, Celltrion and Biocodex; and grants from Biocodex and Janssen. CS declare lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Lilly, Takeda, Tillots. PW received board membership, consultancy, or lecture fees from Abbvie, Amgen, Celltrion, Ferring, Janssen, and Takeda. LV received fees from Abbvie, Amgen, MSD, Ferring, Takeda, Pfizer, Celltrion, Janssen, Galapagos, Dr Falk. RA declares lecture fees from MSD, Abbvie, Pfizer, Takeda, and Janssen. GB received lecture fees from Abbvie, Ferring, Takeda and Pfizer and consultant fees from Takeda, Janssen, Lilly, Celltrion, Sandoz, Abbvie. MB has received lecture fees and travel accommodation from Abbvie, Fresenius Kabi, Janssen, Pfizer and Takeda. DL has received counseling, boards, transports and/or fees from Abbvie, Amgen, Biogen, Ferring, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Tillots. MA has served as a speaker, consultant, and/or advisory board member for Abbvie, Amgen, Biogen, Boehringer-Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech, IQVIA, Janssen, Lilly, MSD, Pfizer, Roche, Takeda, Tillotts. FG declares counseling, boards, transports and lectures fees from Abbvie, Amgen, Biogen, Celltrion, Janssen, Lilly, MSD, Pfizer, Takeda. NR has received lecture fees from AbbVie and Takeda. LP-B received consulting fees from Merck, Abbvie, Janssen, Genentech, Ferring, Norgine, Tillots, Vifor, Shire, Therakos, Pharmacosmos, Pilège, BMS, UCB-Pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer and HAC-Pharma. This author also received lecture fees from Merck, Abbvie, Takeda, Janssen Cilag, Ferring, Norgine, Tillots, Vifor, Therakos, HAC-Pharma and Mitsubishi. No conflicts of interest are claimed by the remaining authors., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Immune checkpoint inhibitors (ICI), i.e., anti-PD1/PDL1 and anti-CTLA-4, have reshaped the prognosis of many cancers. Increased use of ICI has led to the onset of new adverse events. Neurological immune-related adverse events are rare, heterogenous, and potentially life-threatening. Chronic intestinal pseudo-obstruction (CIPO) is an immune-related autonomic plexus neuropathy that may be caused by infiltration of the myenteric plexus by CD8 + T cells. It is a rare and potentially fatal side effect that can be difficult to diagnose early because of initial nonspecific clinical presentation including vomiting, nausea, diarrhea, and constipation. Some rare cases have been described in the literature reporting a frequent resistance to corticosteroids making it necessary to use other immunosuppressive therapy. Vedolizumab is an antibody (Ab) blocking integrin α4-β7 used to treat inflammatory bowel disease. We report the first three cases of ICI-induced CIPO-treated with vedolizumab after corticosteroid failure, with very limited benefits (only one patient with transitory improvement). Based on our results in three cases, vedolizumab does not currently appear to be a therapeutic option. Earlier administration with a standardized dose and frequency schedule may provide better outcomes., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Consent to publish: The authors affirm that human research participants provided informed consent for publication of the images in Figs. 1, 2, 3 and 4., (© 2024. The Author(s).)

This study aims to mine and analyze adverse events (AEs) of Vedolizumab based on the FAERS database to better understand its safety and potential risks in the real world. Data from the second quarter of 2014 to the third quarter of 2023 were collected, employing various signal mining methods such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). The study gathered 14,753,012 reports of AEs, of which 46,726 were related to Vedolizumab. Signal mining identified 401 Preferred Terms (PTs) involving 27 System Organ Classes (SOCs). There was an increasing trend in the number of reports, with a slightly higher proportion of reports from women compared to men, and the primary reporting group was adults, especially those aged between 18 and 65 years. New potential AE signals were identified, such as a higher incidence of Pregnancy, Haematochezia, and Clostridium difficile infection. Although less frequent, strong signals were noted for Incisional hernia, Intestinal fistula infection, Anastomotic complication, Drug metabolising enzyme increased, Gingival graft, Intestinal anastomosis complication, Anorectal infection, Perineal rash, and Abdominal hernia obstructive. Despite the positive prospects of Vedolizumab in the treatment of inflammatory bowel diseases, the AEs related to its use identified in this study, particularly the newly identified potential risks, suggest that even targeted therapies can have systemic effects beyond expectations., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s).)

Background & Aims: Limited data are available on the consequences of prenatal exposure to vedolizumab and ustekinumab. We aimed to compare the safety of vedolizumab and ustekinumab with that of anti-tumor necrosis factor (TNF) in pregnant women with inflammatory bowel diseases (IBD)., Methods: Using nationwide, comprehensive data of the EPI-MERES registry, we identified pregnancies in women with IBD in France, exposed to anti-TNF, vedolizumab, and ustekinumab between 2014 and 2021. We compared pregnancy outcomes and complications in the offspring according to treatment exposure during pregnancy. We applied a propensity score matching for maternal, IBD, and pregnancy characteristics., Results: Three hundred ninety-eight pregnancies exposed to vedolizumab were compared with 1592 pregnancies exposed to anti-TNF; 464 pregnancies exposed to ustekinumab were compared with 1856 pregnancies exposed to anti-TNF. Overall, compared with anti-TNF, neither vedolizumab nor ustekinumab was associated with increased risks of abortion, caesarean section, stillbirth, preterm birth, serious infections, malignancies, or congenital abnormality in children. Women exposed to ustekinumab had an increased risk of small for gestational age births., Conclusions: Overall, the safety of vedolizumab and ustekinumab compared with anti-TNF use during pregnancy is reassuring. Further studies are needed to confirm these findings., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), present ongoing challenges despite advances in pathophysiological understanding and therapeutic options. Current therapies often fail to achieve sustained remission, necessitating exploration of novel treatment targets., Areas Covered: This review explores the role of Tumor Necrosis Factor-like cytokine 1A (TL1A) and its receptor DR3 in IBD pathogenesis, detailing their involvement in mucosal homeostasis and immune modulation. Recent studies on TL1A inhibitors highlight their potential in mitigating inflammation and fibrosis in IBD., Expert Opinion: TL1A inhibition emerges as a promising therapeutic strategy, supported by encouraging outcomes in clinical trials for moderate to severe IBD. Future research may elucidate TL1A's broader impact on immunity, epithelial integrity and fibrosis, offering new avenues for therapeutic intervention and biomarker discovery. Ongoing phase 3 trials are pivotal in assessing TL1A inhibitors as effective and safe treatments for IBD. Additionally, exploration of TL1A's role in fibrosis-associated complications and its potential as a biomarker for treatment response holds promise for personalized medicine approaches. Consideration of TL1A inhibition in concurrent immune-mediated inflammatory diseases suggests broader therapeutic implications beyond gastrointestinal manifestations of IBD.

Background: Biologic therapies are commonly used for inflammatory bowel disease (IBD) patients. Multiple biologic medicines can now be given both intravenously and subcutaneously. The different administration routes present provide different advantages regarding dose escalation, healthcare resource utilisation, pharmacokinetics, convenience and safety. Comparator effectiveness studies between intravenous and subcutaneous administration are lacking., Aim: Our primary outcome was to compare the effectiveness between intravenous and subcutaneous biologics in rates of clinical remission., Methods: We performed a systematic review and meta-analysis to include all relevant articles from MEDLINE ( Ovid ), EMBASE , PubMed and Cochrane Central Register of Controlled Trials from 1 January 2003 to 28 January 2024. Studies that compared intravenous and subcutaneous administration of the same biologic therapy in IBD patients and reported effectiveness outcomes were included. This study was registered on PROSPERO (CRD42023442675)., Results: Twenty studies met the inclusion criteria for the systematic review. Nine vedolizumab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.99; 95% confidence interval: 0.88, 1.11). Six infliximab cohort studies were meta-analysed for clinical remission and no difference was found in clinical remission rates between intravenous and subcutaneous administration (relative risk = 0.91; 95% confidence interval: 0.77, 1.08)., Conclusions: Our findings in the first meta-analysis comparing the effectiveness of intravenous and subcutaneous biologic therapies in IBD suggest there is no difference in the effectiveness between these two administration routes. However, further high-quality studies, particularly head-to-head studies are needed to confirm this finding., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ustekinumab (UST) is an anti-interleukin-12/23 antibody used in the treatment of inflammatory bowel disease. This study includes patients treated at four hospitals in Stockholm to provide long-term real-world data., Methods: Retrospective study including patients diagnosed with ulcerative colitis and treated with UST between the years 2019 and 2021. Patients were followed until withdrawal of treatment, or until a predefined end of study, 31 July 2021. Disease activity was assessed with Physician Global Assessment (PGA); Ulcerative Colitis Endoscopic Index of Severity (UCEIS), laboratory parameters, and drug persistence. The primary outcome was steroid-free remission (PGA = 0) and response (decrease PGA ≥ 1 from baseline) at 3 and 12 months, respectively., Results: A total of 96 patients, 44 women and 52 men were included. The patients had either extensive colitis (69%), left-sided colitis (29%), or proctitis (3%). All but two patients were anti-TNF-experienced; 94 (98%) had failed ≥1, 59 (61%) ≥ 2, and 34 (35%) had failed ≥ 3 anti-TNF drugs. In addition, 28 (29%) had failed vedolizumab. At inclusion, 92/96 patients (96%) had active disease and four patients were in remission. Among patients who were treated with UST, 9/71 (13%) were in steroid-free remission at 3 months, and 26/33 (78%) were at 12 months. Withdrawal rates at 3 and 12 months, were 12 and 26%, respectively, mainly due to persisting disease activity (20%)., Conclusion: In this group of patients with difficult-to-treat ulcerative colitis, UST was shown to be effective in the majority, with high drug persistence at 12 months in combination with a favorable safety profile., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO)., Methods: This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 μg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test., Key Results: The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal., Conclusion & Inferences: The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Aims: Gastro-oesophageal reflux is common in newborns, especially in premature infants. Treatment by medication is controversial as the drugs prescribed have not been consistently proven to be effective and are known to have adverse effects. This study sought to identify trends in the prescription of anti-reflux medication in a large group of French neonatal units., Methods: Data on prescriptions of anti-reflux treatments-proton pump inhibitors (PPIs), antacids, histamine-2 receptor antagonists (H2RAs), and prokinetics-from 2014 to 2022 for infants with a corrected gestational age <45 weeks, were extracted from a prescription database (Logipren®) used by 63 French neonatal units, and then analysed., Results: Of all infants recorded in the database during the study period (n = 152 743), 10.2% (n = 15 650) were prescribed anti-reflux medication (95% confidence interval [CI] 10.0-10.4%), mainly as monotherapy (77.5%). The rate was higher in the subgroup of preterm infants born before 28 weeks of gestation (n = 9493) (20.6%, 95% CI 19.8-21.4%; n = 1956). PPIs were the most commonly prescribed anti-reflux medications (6.9% of infants, 95% CI 6.8-7.0), followed by antacids (5.2%, 95% CI 5.1-5.3%), while H2RAs and prokinetics were rarely prescribed. Over the period, the prescription rate remained stable for PPIs, decreased for H2RAs (τ = -0.86, P = .02), and, among preterm infants born at gestational ages of 28-31 or 32-36 weeks, increased for antacids., Conclusions: Anti-reflux medications were frequently prescribed by neonatal units, especially for extremely premature infants. Most of these prescriptions were for PPIs and antacids., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: This study aimed to compare the efficacy and safety of biologics and small molecules for treatment of adults with moderately-to-severely active ulcerative colitis (UC)., Methods: A systematic literature review was conducted to identify randomised controlled trials evaluating approved and emerging targeted therapies for patients with UC. A Bayesian network meta-analysis (NMA) approach was applied. Outcomes assessed included clinical response and remission, endoscopic mucosal healing, and safety., Results: Thirty studies were included in the NMA following a feasibility assessment comparing approved induction dosing regimens and 22 studies comparing approved maintenance dosing regimens. In the biologic/Janus kinase inhibitor (JAKi)-naïve population, induction studies showed similar clinical response and remission rates across most interventions, with upadacitinib demonstrating significant improvements versus most other interventions. For maintenance studies, mirikizumab demonstrated significant improvements in clinical response and remission versus most other interventions. In the biologic/JAKi-experienced population, no significant differences were observed between most interventions in induction studies, except for significantly improved clinical response and remission for mirikizumab versus adalimumab, and upadacitinib demonstrated significant improvement versus all other interventions. Few differences between active treatments were observed in maintenance studies. In both populations, all active interventions had similar efficacy in terms of endoscopic mucosal healing in both induction and maintenance studies. Regardless of prior treatment exposure, similar rates of serious adverse events were seen across all active interventions in the induction period., Conclusion: Among the available interventions, owing to its favourable efficacy and safety profile, mirikizumab has a relevant role in the long-term treatment of UC., (© 2024. The Author(s).)

A 17-year-old female was diagnosed with inflammatory bowel disease and started on infliximab. A few weeks after starting infliximab, she developed a recurrence of daily fevers associated with an intermittent dry cough, which worsened over the course of a month. A chest radiograph, abdominal ultrasound, and computed tomography scan of the chest and abdomen revealed a heterogeneous spleen with multiple hyperechoic areas, tiny splenic micronodules, and diffuse micronodularity throughout the lungs. She was transferred to a tertiary care hospital because of hypotension, new oxygen requirements, and ongoing fever. Her bloodwork on presentation to tertiary care revealed pancytopenia and elevated inflammatory markers; she had splenomegaly on MRI. As her clinical picture evolved, she continued to have persistent fevers and anorexia despite ongoing management. Infectious diseases, rheumatology, and gastroenterology were consulted to guide the evaluation and management of this patient's complex clinical course., (Copyright © 2024 by the American Academy of Pediatrics.)

Background and Aims: Transition from intravenous (IV) to subcutaneous (SC) administration is an option in inflammatory bowel disease (IBD) with Infliximab (IFX) or Vedolizumab (VDZ). The aim was to compare the adherence, the persistence in therapy, and quality of life (QoL) at baseline, at 6, at 12 months of SC IFX versus SC VDZ., Methods: This was a prospective, observational, multicenter study on patients with IBD in treatment with IV IFX or VDZ who switched to SC. All patients investigated the QoL by the short IBD Questionnaire (sIBDQ) and the concerns and expectations by a 6-item survey. Any adverse events, local and systemic, were reported. Safety, concerns, and satisfaction were evaluated., Results: One hundred and eight out of 93 patients were replaced, 51 to SC IFX and 42 to SC VDZ. The majority accepted the SC route. Persistence in therapy was similar between the two groups. The QoL improved after 6 months (p = 0.004), but at T12 both groups show a significant decline in QoL. SC administration has not caused any concern for patients. As safety, both groups reported a similar number of local reactions (IFX 19.60% vs VDZ 19.04%). In the IFX group were reported more systemic reactions (IFX 11.6% vs VDZ 7.14%) without the need for hospitalization., Conclusion: The transition from IV to SC administration is an appropriate and safe option for treatment with IFX or VDZ. It is very important to consider the patient's choice and preference. The SC administration led to a significant benefit in QoL, especially in the first 6 months of therapy., Competing Interests: Declarations. Conflict of interest: MP served as an advisory board member and/or received lecture grants from AbbVie, Biogen, Galapagos, Janssen, MSD, Pfizer, Takeda Pharmaceuticals. IVB, ES, AMD, EE, IL none conflict of interest. SM served as an advisory board member and/or received lecture grants from AbbVie, Janssen, Takeda Pharmaceuticals. ADL served as an advisory board member and/or received lecture grants from AbbVie, Biogen, Galapagos, Janssen, MSD, Pfizer, Takeda Pharmaceuticals, (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: We aimed to assess the risk of serious infection in patients with inflammatory bowel disease (IBD) treated with vedolizumab compared with those treated with anti-tumor necrosis factors (TNF) and the general population., Methods: In this Swedish cohort study, treatment episodes were identified from nationwide health registers. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infections, defined as infections requiring hospital admission., Results: During 1,376 treatment episodes in Crohn's disease, the rate of serious infections per 100 person-years (PY) was 5.18 (95% CI = 3.98-6.63) with vedolizumab vs 3.54 (95% CI = 2.50-4.85) with anti-TNF; HR = 1.72 (95% CI = 1.12-2.65), partly explained by more gastrointestinal infections. Compared with the rate of 0.75/100 PY (95% CI = 0.59-0.92) in a matched general population cohort, vedolizumab demonstrated higher risk (HR = 7.00; 95% CI = 5.04-9.72). During 1,294 treatment episodes in ulcerative colitis, the corresponding rates were 3.74/100 PY (95% CI = 2.66-5.11) with vedolizumab vs 3.42/100 PY (95% CI = 2.31-4.89) with anti-TNF; HR = 0.80 (95% CI = 0.47-1.36) during the initial 1.1 years and HR = 2.03 (95% CI = 0.65-6.32) after 1.1 years (truncated due to nonproportional hazards). Pneumonia accounted for 40% of all infections among anti-TNF, whereas no case was observed among vedolizumab episodes. Compared with the rate of 0.69/100 PYs (95% CI = 0.53-0.87) in a matched general population cohort, vedolizumab showed an HR of 5.45 (95% CI = 3.67-8.11)., Discussion: Vedolizumab was associated with increased risks of serious infections compared with anti-TNF in Crohn's disease but not in ulcerative colitis. Nonetheless, the panorama of serious infections seemed to differ between the drugs. Our findings underscore the importance of clinical awareness of infections and the safety profile of the 2 therapies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: ReFLECT was a French, prospective, multicenter, observational cohort study evaluating the effectiveness and safety of the infliximab (IFX) biosimilar CT-P13 in a real-world setting. Here, we describe the results for adults with inflammatory bowel disease (IBD)., Methods: Eligible patients with IBD were recruited and received intravenous CT-P13 induction and/or maintenance therapy; patients were either naive to IFX (IFX-naive) or previously treated with IFX originator or another IFX biosimilar (IFX-switched). The primary objective was CT-P13 persistence, which was measured as a time-dependent variable during a two-year follow-up period with four prespecified visits. Safety was assessed., Results: The adult IBD population comprised 530 patients with Crohn's disease (CD), including 327 categorized as IFX-naive, 188 as IFX-switched, 11 as other (i.e., previously received IFX but received another treatment before switching to CT-P13), and 4 with missing data; and 221 patients with ulcerative colitis (UC), including 152 categorized as IFX-naive, 59 as IFX-switched, 8 as other, and 2 with missing data. After two years of follow-up, the rates of CT-P13 persistence were 71.7 % (95 % CI: 66.7, 77.0) and 63.7 % (55.3, 73.3) in patients with CD and UC, respectively. CT-P13 persistence was greater for IFX-switched patients than for IFX-naive patients (CD: 83.7 % [95 % CI: 78.0, 89.9] vs 65.7 % [58.6, 73.7]; UC: 91.2 % [81.7, 100.0] vs 53.4 % [43.0, 66.2]). The main reason for CT-P13 discontinuation was loss of response (CD/UC) in both IFX-naive (14.7 %/21.7 %) and IFX-switched (7.4 %/5.1 %) groups. Among patients (CD and UC, respectively), 51.3 % and 45.2 % reported ≥1 adverse event (AE), and 13.2 % and 12.7 % reported serious AEs, respectively., Conclusion: After two years of follow-up, the effectiveness of intravenous CT-P13 was maintained in >80 % of IFX-switched patients. CT-P13 induced effective therapeutic maintenance in IFX-naive patients. CT-P13 had an acceptable safety profile., Trial Registration: ClinicalTrials.gov identifier: NCT02925338., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D. Laharie: Counseling, boards, transports, or fees: AbbVie, Amgen, Biogen, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galápagos NV, Janssen Pharmaceuticals, MSD, Pfizer, Prometheus Laboratories, Roche, Takeda Pharmaceuticals. Y. Bouhnik: Research grants: AbbVie, Amgen, Fresnius Kabi, Janssen Pharmaceuticals, Takeda Pharmaceuticals, Viatris Inc. Consulting fees: AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Fresnius Kabi, Galápagos NV, Gilead Sciences Inc, Hospira, Iterative Health, Janssen Pharmaceuticals, Mayoly Spindler, Merck & Co., Inc, MSD, Norgine, Pfizer, Roche, Sandoz, Sanofi, Takeda Pharmaceuticals. Payment/honoraria: AbbVie, Celltrion, Eli Lilly, Fresnius Kabi, Galápagos NV, Gilead Sciences Inc, Janssen Pharmaceuticals, MSD, Pfizer, Takeda Pharmaceuticals. L. Vuitton: Lecture and/or consulting fees: AbbVie, Amgen, Celltrion, Dr Falk Pharma GmbH, Eli Lilly, Galápagos NV, Janssen Pharmaceuticals, Pfizer, Takeda Pharmaceuticals, Viatris Inc. A. Biron: Research grants: AbbVie, Amgen, Biogen, Celltrion, Ferring Pharmaceuticals, Takeda Pharmaceuticals, Tillotts Pharma. Consulting fees: Biogen, Ferring Pharmaceuticals. Lecture fees: AbbVie, Amgen, Takeda Pharmaceuticals, Tillotts Pharma. Travel accommodation fees: Amgen, Celltrion. A. Amiot: Consulting fees: AbbVie, Adacyte Therapeutics, Fresenius Kabi, Gilead Sciences Inc, Janssen Pharmaceuticals, Pfizer, Takeda Pharmaceuticals, Tillotts Pharma. Lecture fees: AbbVie, Adacyte Therapeutics, Biogen, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, MSD, Pfizer, Takeda Pharmaceuticals, Tillotts Pharma. Travel accommodation fees: AbbVie, Adacyte Therapeutics, Biogen, Janssen Pharmaceuticals., (Copyright © 2024. Published by Elsevier Masson SAS.)

Antitumor necrosis factor (TNF)-alpha (TNFa) drugs are crucial for treating inflammatory bowel disease (IBD) but may increase opportunistic infection risk. Among such infections, sporotrichosis is a chronic granulomatous disease caused by saprophytic dimorphic fungi of the genus Sporothrix, which occurs worldwide. To date, there have been no reports of sporotrichosis in immunosuppressed IBD patients. The main objectives are to discuss clinical, diagnostic, and therapeutic aspects of sporotrichosis in IBD patients on anti-TNF therapy. We describe three patients with IBD on TNFa therapy who contracted cutaneous-disseminated and extracutaneous sporotrichosis and discuss strategies for managing sporotrichosis and IBD therapy in this scenario. The first case is a patient with ulcerative colitis with mild lymphocutaneous sporotrichosis who did not require discontinuation of anti-TNF agents and methotrexate. The other two patients had rapidly progressive extensive lymphocutaneous disease and disseminated sporotrichosis. These patients required hospitalization, a temporary discontinuation of their biological therapy, and a subsequent switch to vedolizumab. In all cases, the sporotrichosis was successfully treated and none of them experienced serious complications. Sporotrichosis should be considered in anti-TNF IBD patients with opportunistic infections. Early diagnosis, infection treatment, education of cat owners, and population control programs are necessary., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Octreotide is recommended as a second-line treatment for patients with congenital hyperinsulinism (CHI), especially for those who do not respond to diazoxide or surgical intervention. Studies on the adverse effects of octreotide in large cohorts are still scarce. We evaluated the safety of octreotide in CHI patients by reviewing cases from the two largest centres in China that specialize in the management of this condition. Our study analysed adverse events in 122 CHI patients on octreotide, with a 93% success rate for the therapy alone. The mean maximum dose of octreotide was 13.1 ± 6.5 µg/kg/day, with no difference in required doses between diffuse and focal lesion patients. Common side effects were hepatobiliary injuries (20.5%), gastrointestinal symptoms (31.1%), and transient hyperglycaemia (49.2%), with one case of necrotizing enterocolitis. Adverse event rates increased in patients treated with intermediate octreotide dose to those treated with higher doses, rising from 58% at doses of 5-10 µg/kg/day to 100% at doses exceeding 20 µg/kg/day. Patients experiencing adverse events received significantly higher doses., Conclusion: Octreotide effectively maintained blood glucose levels in diazoxide-unresponsive CHI patients without serious adverse effects, across all subtypes. Our study suggests that intermediate octreotide dosing is associated with a lower incidence of adverse events. We recommend close monitoring of patients receiving octreotide, especially during the initiation phase and when higher doses are administered., What Is Known: • Octreotide is a commonly used second line treatment for patients with congenital hyperinsulinism. • The administration of octreotide is frequently associated with gastrointestinal adverse events., What Is New: • Our study indicates that octreotide is used without serious adverse effects to maintain blood glucose levels in infants with congenital hyperinsulinism who are otherwise in good health. • The incidence of adverse events in patients treated with octreotide is dose-dependent., Competing Interests: Declarations. The studies involving humans were approved by Children’s hospital of Fudan University (2017-130). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The medical treatment of ulcerative colitis (UC) includes the use of biological agents such as vedolizumab, a gut-selective alpha4beta7 (ɑ4β7) antagonist. The mechanism of action of vedolizumab involves interfering with leukocyte trafficking into the gut vasculature, which halts inflammation. Due to this mechanism of action, concerns have arisen regarding an increased risk of gut infections, specifically, clostridium difficile infection (CDI). The aim is to provide clarity regarding the association between the use of vedolizumab as a therapy for ulcerative colitis and the risk of developing CDI., Methods: A systematic literature review was conducted, starting with the scoping search, followed by backward snowballing parallel with keyword-based search to identify related articles. A quality assessment was conducted on the initially selected articles and excluded low-quality papers., Results: Pooled analyses indicated that there was no significant association between the use of vedolizumab and the risk of developing CDI (effect size = 0.03 [-0.02, 0.07])., Conclusions: Vedolizumab does not increase the risk of CDI in patients with UC. Further studies are needed to confirm these findings., (Copyright © 2024 Copyright: © 2024 Saudi Journal of Gastroenterology.)

Background and Objective: Rifaximin is used to treat diarrhea-predominant irritable bowel syndrome (IBS-D). However, determining the most effective regimen remains a challenge. This study aimed to evaluate the effectiveness and safety of a 10-day high-dose course of rifaximin (2200 mg/day) and its effects on both abdominal symptoms and quality of life (QOL) in patients with IBS-D., Method: Adult patients with moderate to severe IBS-D (Rome IV) and fecal urgency and bloating were prescribed rifaximin 1100 mg twice daily for 10 days. Demographic information, the IBS Symptom Severity Index (IBS-SSI) score (using a 7-point Likert scale), and Bristol Stool Scale (BSS) score were recorded at baseline, day 10, and 4 weeks after treatment cessation. IBS Symptom Severity Score (IBS-SSS) and IBS-QOL scores were recorded at baseline and day 10. Any drug adverse effects were recorded., Results: In total, 39 patients completed the study. Average scores for all abdominal symptoms and BSS showed significant improvement at day 10 and 4 weeks after treatment cessation (all p < 0.001). A significant improvement was seen in IBS-SSS and overall IBS-QOL score at day 10 (p < 0.001), with the highest improvement (31%) in interference with activity. Moreover, composite improvement rates were 38.64% for all abdominal symptoms, together with BSS < 5, bi-composite (66.67% for abdominal pain + bloating; 61.54% for abdominal pain + urgency), and 56.41% for tri-composite (abdominal pain + bloating + urgency) symptoms. Notably, no serious adverse effects were reported, and the adherence rate was 94.9%., Conclusions: Abdominal symptoms and overall QOL, especially in social and work dimensions, significantly improved in patients with moderate to severe IBS-D following a regimen of rifaximin 2200 mg/day, which was well tolerated., Competing Interests: Declarations Conflict of interest Marjan Mokhtare, Maryam Fathi, Amir M. Sadeghian, Mohammad-Javad Sotoudeheian, and Abolfazl Namazi have no conflicts of interest that are directly relevant to the content of this article. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Ethics approval This study and all study-related procedures were approved by the medical ethics committee of Iran University of Medical Sciences, Tehran, Iran (approval date 2023-06-11; ethics committee reference number: IR.IUMS.FMD.REC.1402.135) and so registered in the Iranian Registry of Clinical Trials (IRCT20141201020178N12). Consent to participate Informed consent was obtained from all individual participants included in the study. Consent to publication Not applicable. Data availability statement The data used in this study are accessible upon a reasonable request to the corresponding author. Code availability Not applicable. Author contributions All authors contributed to the study's conception and design. Marjan Mokhtare, Maryam Fathi, Amir M. Sadeghian, and Mohammad-Javad Sotoudeheian prepared the material and collected and analyzed the data. Marjan Mokhtare and Abolfazl Namazi wrote the first draft of the manuscript, and all authors commented on subsequent versions. All authors read and approved the final manuscript., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC., Methods: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed., Findings: Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study., Interpretation: Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3., Funding: Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag., Competing Interests: Declaration of interests MCC is supported by a Gandel Major Philanthropy Grant and an Australian Postgraduate Award, and has received research funding from Janssen-Cilag. CFDLWS has served as a speaker for DiaSorin, has received educational support from Pfizer, Shire, and Ferring, has received research funding from the Robert C Bulley Charitable Foundation and St Vincent's Hospital Melbourne Research Endowment Fund, and is supported by an Australian National Health and Medical Research Council (NHMRC) Postgraduate Scholarship. DC has received educational support from Viatris and is supported by an NHMRC Postgraduate Scholarship. EKW has served as a consultant, advisory board member, or speaker for AbbVie, Bristol Myers Squibb, Ferring, Janssen, Celltrion, Falk, and Takeda, is supported by an NHMRC Emerging Leadership Level 1 Fellowship, and has received research support from Ferring and Janssen. AP has served as an advisory board member or received speaker fees from AbbVie, Ferring, Janssen, Pfizer, Takeda, and Dr Falk Pharma. BC has served as a consultant, advisory board member, or speaker for AbbVie, Celltrion, Chiesi, Ferring, Janssen, Eli Lilly, MSD, Pfizer, Takeda, and Shire, and has received research support from AbbVie, Celltrion, The Gastroenterological Society of Australia, the Helmsley Charitable Trust, the NHMRC, and Takeda. WN has received educational and research support from Pfizer, AbbVie, Janssen, Shire and Ferring. JB has served as a consultant, advisory board member, or speaker for AbbVie, Ferring, Janssen, Celltrion, Chiesi, Janssen, Pfizer, Amgen, GlaxoSmithKline, Bristol Myers Squibb, Microba, Anatara, and Takeda, and has received research support from the NHMRC, United States Department of Defense, AbbVie, Janssen, Ferring, Pfizer, and Takeda. MG has served on the advisory board of Pfizer and AbbVie and has received speaker fees and research grants from Abbvie, Celltrion, Janssen, Pfizer and travel grants from Pfizer. NM has received speaker fees from Takeda and Baxter, and educational support from Baxter. DRVL has received consulting fees from AbbVie and speaker fees for Takeda. NSD reports serving as an advisory board member or speaker for AbbVie, Celltrion, Chiesi, Ferring, Janssen, Eli Lilly, MSD, Pfizer, Takeda, and Shire, and has received research support from AbbVie, Celltrion, The Gastroenterological Society of Australia, and the NHMRC. RWL reports advisory board membership for AbbVie, Aspen, Bristol Myers Squibb, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda, and research grants from the University of Sydney, the McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Joanna Tiddy grant, the Gastroenterological Society of Australia, the NHMRC, The Gutsy Group, and Pfizer. MPS has received educational grants or research support from Gilead and Celltrion, speaker fees from Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Celltrion, Eli Lilly, and Dr Falk Pharma, and has served on advisory boards or received consultancy fees for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead, Bristol Myers Squibb, Celltrion, and Eli Lilly, and has received travel grants from Pfizer and Dr Falk Pharma. PDC has served as a consultant, advisory board member, or speaker for AbbVie, Baxter, Ferring, Janssen, Celltrion and Emerge Health, and is supported by a NHMRC Emerging Leadership Level 2 Fellowship, and has received research support from AbbVie, Ferring, Janssen and Pfizer. All other authors declare no competing interests., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To review the pharmacologic and clinical profile of mirikizumab in the treatment of moderate to severe ulcerative colitis (UC)., Data Sources: A PubMed search was performed from inception to December 2023 using keywords mirikizumab, interleukin-23 inhibitor , and UC . Information was also obtained from package inserts as well as published abstracts., Study Selection and Data Extraction: Phase 3 studies plus relevant literature on mirikizumab pharmacologic and clinical profile were reviewed., Data Synthesis: Mirikizumab approval was based on LUCENT-1 and LUCENT-2. In the phase 3 studies involving patients with moderate to severe UC, mirikizumab, when compared to placebo, resulted in clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, mirikizumab met the secondary endpoints of alternate definition of clinical remission, endoscopic remission, glucocorticoid-free clinical remission, histologic-endoscopic mucosal remission, and improvement in bowel urgency status, bowel-urgency remission, and maintenance of clinical remission. Common adverse events noted include infection (15.1%), injection-site reaction (8.7%), nasopharyngitis (7.2%), and headache (3.3%)., Relevance to Patient Care and Clinical Practice in Comparison to Existing Agents: Mirikizumab is the first selective interleukin 23 (IL-23) inhibitor approved for UC. Additional studies are required to determine how to position mirikizumab in both biologic-naïve and biologic-experienced patients with moderate to severe UC., Conclusion: Mirikizumab provides a novel mechanism of action for the treatment of moderate to severe UC and is another welcomed treatment advance in the treatment arsenal, providing a more selective mechanism of action while maintaining a comparable safety profile., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DC has served on the speaker bureau for Janssen Pharmaceuticals and has served as a consultant to Bristol Myers Squibb, and Boehringer Ingelheim, Abbvie, Janssen Pharmaceuticals. SB has served as a consultant to Bristol Myers Squibb, Prometheus Laboratories, Pfizer, AbbVie, and Boehringer Ingelheim. HS has no conflicts of interest to declare.

Background: Inflammatory bowel disease (IBD) is a chronic, relapsing condition wherein biologics have improved disease prognosis but introduced elevated infection susceptibility. Vedolizumab (VDZ) demonstrates unique safety advantages; however, a comprehensive systematic comparison regarding the risk of Clostridioides difficile infection (CDI) between vedolizumab and alternative medications remains absent., Method: Medline, Embase, Cochrane, and clinicaltrials.gov registry were comprehensively searched. Pooled estimates of CDI proportion, incidence, pooled risk ratio between ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab and other medications were calculated. Data synthesis was completed in R using the package "meta"., Results: Of the 338 studies initially identified, 30 met the inclusion/exclusion criteria. For CDI risk, the pooled proportion was 0.013 (95% CI 0.010-0.017), as well as the pooled proportion of serious CDI was 0.004 (95% CI 0.002-0.008). The comparative pooled risk ratios revealed: UC versus CD at 2.25 (95% CI 1.73-2.92), vedolizumab versus anti-TNF agents at 0.15 (95% CI 0.04-0.63) for UC and 1.29 (95% CI 0.41-4.04) for CD., Conclusion: The overall CDI risk in IBD patients exposed to vedolizumab was estimated to be 0.013. An increased risk of CDI was noted in UC patients receiving vedolizumab compared to those with CD. Vedolizumab potentially offers an advantage over anti-TNF agents for UC regarding CDI risk, but not for CD., Trial Registration: The study was registered on the PROSPERO registry (CRD42023465986)., (© 2024. The Author(s).)

Background & Aims: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population)., Results: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified., Conclusions: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction., Clinicaltrials: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Evidence on the comparative efficacy and safety of approved therapies for ulcerative colitis (UC) during induction and maintenance, including upadacitinib (UPA), vedolizumab (VEDO), ustekinumab (UST), and tofacitinib (TOFA), is limited., Methods: Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30 mg, VEDO 300 mg intravenously every 8 weeks (Q8W), UST 90 mg SC Q8W, or oral TOFA 5 mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator., Results: The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15 mg versus VEDO and TOFA (p < 0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30 mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators., Conclusion: In patients with active UC, greater clinical efficacy, and similar safety after 1 year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist., (© 2024. The Author(s).)

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).)

Introduction: Therapeutic Drug Monitoring (TDM) has an important role in the management of inflammatory bowel disease (IBD) patients on infliximab (IFX) or adalimumab and is recommended in IBD patients presenting a loss of response under anti TNF agent. But, TDM was not recommended for others biotherapies., Areas Covered: Analyzing all publications about TDM and biologics in IBD patients, we reported the major results for each biotherapy., Expert Opinion: Emerging data suggest that TDM will probably be similarly useful forIFX SC. In contrast, there is no demonstrated clinical benefit to the use of TDM with golimumab. For vedolizumab results for the use of both reactive and proactive TDM are discordant. For ustekinumab, data supports the existence of an exposure response relationship, albeit of a lesser magnitude than with anti-TNF agents. Finally, recent data from small case series suggests that TDM could be valuable in optimizing anti-IL23 agents, particularly risankizumab, but this requires further clarification. Consistent with the new concept of 'proactive' strategy, recent data support the utility of dashboard-driven model informed precision dosing (MIDP) of anti-TNF agents, in particular infliximab. Dashboards are software systems using Bayesian population pharmacokinetic modelling to individualize recommendations for target drug levels.

Introduction: Remission rates for ulcerative colitis (UC) remain low despite significant progress in disease understanding and the introduction of novel therapeutic agents. Several challenges contribute to this, including the heterogeneity of the disease, suboptimal efficacy of current diagnostic and therapeutic tools, drug safety concerns, and limited access to newer treatment options., Areas Covered: This review evaluates current treatment targets in UC, assessing the effectiveness of various therapies and management strategies in achieving remission. We explore the potential role of personalized medicine, which tailors treatment based on clinical predictors, genetic factors, and immunologic profiles. Personalized approaches show promise in improving remission rates by addressing the unique characteristics of each patient. We also discussed the feasibility of adapting such management models and suggested solutions to some of the challenges in their implementation., Expert Opinion: Future efforts should prioritize the continued development of biologics, small molecules, and digital health solutions, alongside noninvasive monitoring techniques. These innovations could not only enhance patient outcomes by improving remission rates but also reduce healthcare costs by minimizing hospitalization and surgical interventions. Ultimately, a personalized, stratified approach to UC management is key to optimizing patient care and addressing the unmet needs in this field.

Competing Interests: The authors declare no conflict of interest.

Introduction: Medication holidays in inflammatory bowel disease (IBD) offer a potential means to balance disease management, costs, and quality of life. This concept is increasingly relevant in light of the chronic nature of IBD, the cumulative side effects associated with long-term pharmacotherapy, and the evolving treatment landscape that now includes a large armamentarium of effective induction, maintenance, and rescue therapies paired with disease monitoring tools that enable early intervention., Areas Covered: This review critically examines the rationale, implementation, and risks of medication holidays in IBD. Recent evidence is reviewed to help guide the risks of relapse involved with cessation of therapy. The selection criteria for patients, the necessary monitoring protocols, and strategies for managing potential relapses are outlined., Expert Opinion: Despite the potential benefits, medication holidays in IBD involve significant risks and require careful patient selection and active management. Current research highlights a need for improved predictive models and a deeper understanding of patient-specific outcomes and consequences. The future of medication holidays will depend heavily on advancements in noninvasive monitoring technologies and more personalized approaches to therapy. Ultimately, establishing clearer guidelines for safely conducting medication holidays will be crucial in integrating this strategy into routine clinical practice.

Ulcerative colitis (UC) is a serious health problem that requires a constant need to identify new effective drugs. The aim of this study was to assess the efficacy and safety of mirikizumab compared with other biologic drugs approved for the treatment of moderately to severely active UC. This systematic review with frequentist network meta-analysis (NMA) included randomized controlled trials (RCTs) that evaluated the use of adalimumab, golimumab, infliximab, mirikizumab, vedolizumab, and ustekinumab compared with placebo or with another approved biologic drug. The NMA was conducted using the netmeta R software package. The P score was used to determine the treatment ranking. A total of 14 RCTs were included in the analysis. No significant differences were observed in the incidence of clinical response and remission between mirikizumab and other drugs. Mirikizumab was superior to placebo for clinical response (induction: odds ratio [OR] = 2.38; 95% confidence interval [CI]: 1.63-3.48; maintenance: OR = 3.31, 95% CI: 1.59-6.89) and remission (induction: OR = 2.09, 95% CI: 1.20-3.63; maintenance: OR = 2.96; 95% CI: 1.62-5.40). The probability plot indicated that infliximab might be the most effective option in terms of both clinical response and remission (P score, 0.8971 and 0.8814, respectively) in induction phase. No significant differences were noted between the studied drugs in any adverse events (AEs), serious AEs (SAEs) and infections for the induction phase, and in any AEs, infections and serious infections for the maintenance phase. The drugs differed in terms of discontinuation due to AEs (induction and maintenance phases) as well as SAEs and serious infections (maintenance phase). Mirikizumab did not differ from other biologics in terms of clinical response and remission for both induction and maintenance phases in patients with UC. Mirikizumab during the induction phases achieved rank 3 for clinical response and rank 5 for clinical remission. Therefore, it represents a valuable treatment option. The lack of significant differences in the risk of AEs and SAEs suggests that mirikizumab has a similar safety profile to the other drugs., (© 2024 Pharmacotherapy Publications, Inc.)

Introduction: Inflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn's Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD., Aim: This study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD., Method: This study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn's Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period., Results: In the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002)., Conclusion: Both IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients., Clinical Trial Registration: This study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022)., (© 2024. The Author(s).)

Background and Aims: Vedolizumab is a humanized gut selective drug that targets α4β7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related., Methods: Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI)., Results: The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately., Conclusions: The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.

Background: Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia and, subsequently, colorectal cancer (CRC) owing to chronic inflammation. Patients may also experience other severe disease complications, such as hospitalization and surgery. Several biologics are available for the treatment of patients with IBD and some patients require multiple lines of treatment owing to loss of response or tolerability to their prescribed biologic. Previous studies suggest that the choice of initial biologic treatment may impact the outcomes of later treatment lines. In this study, we assessed adverse clinical outcomes in patients with Crohn's disease (CD) or ulcerative colitis (UC) who received different biologic treatment sequences., Methods: ROTARY part B was a retrospective cohort study using the Optum® Clinical Database that evaluated the incidences of IBD-related hospitalization, IBD-related surgery, dysplasia, CRC, and infections in patients with CD or UC who received two biologics successively. First-line biologics included adalimumab, infliximab, ustekinumab (CD only), and vedolizumab; second-line biologics included infliximab and adalimumab., Results: In patients with CD, the treatment sequence of ustekinumab to infliximab was associated with the highest overall incidences of hospitalization (51.9%), surgery (40.7%), CRC (3.7%), and infection (37.0%). Vedolizumab followed by an anti-tumor necrosis factor alpha (anti-TNFα) treatment was associated with a significantly lower risk of experiencing an adverse medical event (hospitalization, surgery, or infection) than two successive anti-TNFα treatments (odds ratio, 1.526; 95% confidence interval, 1.004-2.320; P < 0.05). In patients with UC, the treatment sequence of vedolizumab to adalimumab resulted in the lowest overall incidence of adverse outcomes (20.3%, 6.3%, 0.0%, 6.3%, and 4.7% for hospitalization, surgery, CRC, dysplasia, and infection, respectively)., Conclusions: We describe differences in adverse clinical outcomes associated with sequencing of biologics in patients with CD or UC and demonstrate favorable results in patients who received vedolizumab as a first-line biologic. These results provide potential guidance to clinicians choosing sequences of biologic treatments in patients with IBD., (© 2024. Takeda Pharmaceuticals.)

Background: Very early onset inflammatory bowel disease (VEOIBD) is defined as disease onset in patients younger than 6 years. Challenges in treatment of VEOIBD include lack of approved therapies and increased incidence of monogenic immunodeficiencies. We report on patterns of anti-TNF use, efficacy, and safety in a large cohort of patients with VEOIBD., Methods: Very early onset inflammatory bowel disease patients receiving care at a single center were prospectively enrolled in a data registry and biorepository starting in 2012. Whole exome sequencing was available to all patients. Clinical data including IBD medication use and response were extracted from the medical record. We examined antitumor necrosis factor (anti-TNF) cumulative exposure and time to failure and evaluated the effect of covariates on anti-TNF failure using Cox proportional hazard regression., Results: In this cohort of 216 VEOIBD patients with median 5.8-year follow-up, 116 (53.7%) were TNF-exposed. Sixty-two TNF-exposed patients (53.4%) received their first dose at younger than 6 years. Cumulative exposure to anti-TNF was 23.6% at 1 year, 38.4% at 3 years, and 43.4% at 5 years after diagnosis. Cumulative exposure was greater in patients with Crohn's disease (P = .0004) and in those diagnosed in 2012 or later (P < .0001). Tumor necrosis factor failure occurred in 50.9% of those exposed. Features predictive of anti-TNF failure included ulcerative colitis/IBD-unclassified (hazard ratio, 1.94; P = .03), stricturing (hazard ratio, 2.20; P = .04), and younger age at diagnosis (hazard ratio, 1.25; P = .01). Adverse events occurred in 22.6% of infliximab-exposed and 14.3% of adalimumab-exposed., Conclusions: Efficacy and safety of anti-TNFs in VEOIBD is comparable to what has previously been reported in older patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. 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: Subcutaneous [SC] infliximab may provide multiple benefits over intravenous [IV] formulations. However, studies for efficacy and safety in inflammatory bowel disease [IBD] have been constrained by small sizes that limit the interpretation of outcomes, particularly for subgroups potentially at high risk of disease relapse., Methods: We conducted a systematic review and random-effects meta-analysis up to January 2023, to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis., Results: We identified 15 studies of patients established ≥ 3 months on IV infliximab, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease [CD], or perianal CD [p = 0.55 and p = 0.11 at 9-12 months, and p = 0.50 at 6 months, respectively]. Neither prior IV dose [≤ 10 mg/kg 6-weekly] [p = 0.48] nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (p = 0.48 and p = 0.45 [UC vs CD], respectively)., Conclusion: Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and a low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10 mg/kg 6-weekly. These data should provide patients and clinicians alike with confidence in SC infliximab use in IBD., (© The Author(s) 2024. 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.)

Ustekinumab and vedolizumab are key treatment options for Crohn's disease patients who fail anti-tumor necrosis factor (TNF) therapy. This updated meta-analysis aims to compare the efficacy and safety of these two drugs. We performed a systematic review in PubMed, Embase , and Cochrane databases searching for randomized and nonrandomized studies comparing vedolizumab versus ustekinumab in patients with Crohn's disease with previous anti-TNF failure or intolerance. The primary outcome was steroid-free clinical remission (SFR) at the pos-induction (12-16 weeks) and maintenance period (48-52 weeks). The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I2 statistics. This meta-analysis included 11 studies and 2724 patients. There was a significant difference favoring ustekinumab in SFR at pos-induction (OR, 1.44; 95% CI, 1.11-1.88; P  = 0.006; I2  = 27%) and maintenance periods (OR, 1.86; 95% CI, 1.23-2.82; P  = 0.003; I2  = 80%), in clinical remission at pos-induction period (OR, 2.04; 95% CI, 1.58-2.63; P  < 0.001; I2  = 3%), and in treatment discontinuation due to adverse events (OR, 0.31; 95% CI, 0.16-0.60; P  < 0.001; I2  = 0%). In patients with Crohn's disease with prior anti-TNF failure, ustekinumab showed higher SFR during both the pos-induction and maintenance period and a lower rate of treatment discontinuation due to adverse events., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Effectiveness and safety of advanced therapies for ulcerative colitis (UC) warrant assessment in the real world., Objective: To perform a systematic review and summarize real-world evidence of advanced therapies approved for moderate-to-severe UC., Methods: A systematic literature review was conducted using real-world studies of biologics or small molecules in UC using Embase, MEDLINE, and MEDLINE-In Process databases. Only products approved in any jurisdiction during the search were included. English-language full-papers (January 2005 to February 2022) and congress abstracts (January 2019 to February 2022) were included. Studies with less than 30 patients or only biologic-naive patients were excluded., Results: A total of 139 studies were included out of 3,930 identified articles (75%, published between 2019 and 2022; 64%, retrospective observational; 53%, from 5 countries [Italy, United States, Spain, United Kingdom, and Belgium]). Most studies were single agent (highest: vedolizumab = 50, tofacitinib = 24, and adalimumab = 18), and rates of clinical remission (CR) and adverse events varied widely. From the published comparative effectiveness studies (16), the rates of CR were numerically higher with vedolizumab vs anti-tumor necrosis factor (TNF)-α agents. Compared with vedolizumab, the effectiveness of tofacitinib was numerically greater in CR (occasionally significant). Rates of steroid-free CR were comparable between ustekinumab and tofacitinib. Infliximab was the most effective anti-TNFα agent, as reported by 2 studies. Remarkably, adverse events were similar across therapies in comparative studies., Conclusions: Vedolizumab and tofacitinib were the most assessed therapies. In comparative studies, remission rates were numerically higher with tofacitinib vs vedolizumab and for vedolizumab vs anti-TNFα. Tofacitinib was comparable with ustekinumab for steroid-free CR. Safety was comparable across therapies. Future studies should explore the literature gaps identified, including limited comparative studies with small sample sizes, variations in study designs and patient characteristics, varied definitions of CR, and limited use of patient-reported outcome measures in real-world settings.

Background and Aim: Extraintestinal manifestations (EIMs) pose a significant threat in inflammatory bowel disease (IBD) patients. Vedolizumab (VDZ) primarily affects the gastrointestinal tract. However, its impact on EIMs remains uncertain. Therefore, we conducted this meta-analysis to examine the effects of VDZ on EIMs during treatment., Methods: Relevant studies were identified by conducting thorough searches across electronic databases, including PubMed, Ovid Embase, Medline, and Cochrane CENTRAL. Primary outcomes focused on the proportion of patients with resolution for pre-existing EIMs in IBD patients receiving VDZ. Secondary outcomes included the proportion of patients with EIM exacerbations and new onset EIMs during VDZ treatment., Results: Our meta-analysis encompassed 21 studies. The proportion of patients with resolution of pre-existing EIMs in VDZ-treated IBD patients was 39% (150/386; 95% confidence interval [CI] 0.31-0.48). The proportion of patients with EIM exacerbations occurred at a rate of 28% (113/376; 95% CI 0.05-0.50), while new onset EIMs had a rate of 15% (397/2541; 95% CI 0.10-0.20). Subgroup analysis revealed a 40% (136/337) proportion of patients with resolution for articular-related EIMs and a 50% (9/18) rate for erythema nodosum. Exacerbation rates for arthritis/arthralgia, erythema nodosum/pyoderma gangrenosum, and aphthous stomatitis during VDZ use were 28% (102/328), 18% (7/38), and 11% (3/28), respectively. The incidence rate of newly developed EIMs during treatment was 11% (564/4839) for articular-related EIMs, with other EIMs below 2%., Conclusion: VDZ demonstrates efficacy in skin-related EIMs like erythema nodosum and joint-related EIMs including arthritis, arthralgia, spondyloarthritis, and peripheral joint diseases. Some joint and skin-related EIMs may experience exacerbation during VDZ therapy., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: A temporal relationship between vedolizumab and new-onset spondyloarthritis (SpA) has been suggested., Aims: We evaluated the relationship between vedolizumab initiation and development of new-onset SpA in patients with inflammatory bowel disease (IBD) through serial clinical evaluation and magnetic resonance imaging (MRI)., Methods: A single-centre prospective observational study of 24 patients with IBD. Patients were eligible if they had active ulcerative colitis or Crohn's disease (CD), were initiating vedolizumab, had no prior history of arthritis or SpA and were suitable for serial MRI. A rheumatologist performed clinical evaluation prior to the first dose and 8 and 24 weeks. Axial MRI was evaluated by a blinded central reader and performed at baseline 8 and 24 weeks., Results: Nine tumor necrosis factor (TNF) inhibitor-naïve patients (4 male; mean age 53.2 years; 6 UC; 3 CD) and eight TNF inhibitor-experienced patients (7 male; mean age 48 years; 3 UC; 5 CD) completed all assessments. No patients developed new features of axial arthritis or features of peripheral SpA (inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp)). Both groups demonstrated a good intestinal response., Conclusion: Vedolizumab initiation did not induce new features of axial or peripheral SpA after 24 weeks of treatment in TNF inhibitor-experienced or TNF inhibitor-naive patients with IBD., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: As new therapies for the treatment of Crohn's disease (CD) are approved, there is an increasing need for evidence that clarifies their positioning and sequencing., Areas Covered: Comparative effectiveness research (CER) aims to inform physicians' decisions when they choose which intervention (drug or treatment strategy) to administer to their patients. Pragmatic head-to-head trials represent the best tools for CER, but only a few have been published in the IBD field. Network meta-analyses can point toward the superiority of one drug over another, but they do not reflect everyday clinical practice. Finally, real-world evidence complements that coming from head-to-head trials and network meta-analyses, assessing the real-life effectiveness of therapeutic interventions., Expert Opinion: There is insufficient evidence to create a definitive therapeutic algorithm for CD, but some general considerations can be made. Anti-TNF-α agents seemingly represent the most 'sustainable' first-line choice, considering benefit-harm ratio and costs; vedolizumab, ustekinumab, and risankizumab may be considered as first-line choice when safety issues become prominent. In the event of pharmacodynamic failure, out-of-class swap is to be preferred - possibly with anti-IL23p19 as the best option, with unclear data regarding upadacitinib positioning; a second anti-TNF-α could be considered, as a second choice, after pharmacokinetic failure.

Background: Tumor necrosis factor (TNF-α) inhibitors and the α4β7 integrin antagonist, vedolizumab, have been investigated as treatment options for patients with steroid-refractory microscopic colitis., Aims: To evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory microscopic colitis., Methods: Retrospective studies and case series involving patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Pooled proportional meta-analyses were used to calculate the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Statistical analysis was performed in R using the metafor and meta packages., Results: A total of 14 studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% [95% CI (0.483; 0.776), I 2 =43% P =0.08], 57.8% [95% CI (0.3895; 0.7571), I 2 =0%, P =0.7541], and 39.3% [95% CI (0.0814; 0.7492), I 2 =66%, P =0.02] for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rates were 65.9% [95% CI (0.389; 0.889), I 2 =67%, P =0.02], 45.3% [95% CI (0.1479; 0.7747), I 2 =0%, P =0.36] and 32.5% [95% CI (0.000; 0.8508), I 2 =53%, P =0.14] in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biological-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively., Conclusion: Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory microscopic colitis and with a tolerable safety profile. Future randomized controlled trials are needed to compare vedolizumab with TNF-α inhibitors and examine treatment effect on patients' quality of life., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Data from phase IIb/III and phase III studies were used to characterize the population pharmacokinetics of risankizumab and its exposure-response relationships for efficacy and safety in ulcerative colitis (UC) patients. A two-compartment model with first-order absorption and elimination accurately described risankizumab pharmacokinetics. Although certain covariates, namely, body weight, serum albumin, fecal calprotectin, sex, corticosteroid use, advanced therapy inadequate response, and pancolitis, were statistically correlated with risankizumab clearance, their impact on exposure was not clinically meaningful for efficacy or safety. Phase II exposure-response analyses demonstrated that the 1,200 mg intravenous (IV) induction dose at Weeks 0, 4, and 8 achieved near maximal response for all efficacy end points, with suboptimal efficacy from the 600 mg and little added benefit from the 1,800 mg regimens, justifying 1,200 mg IV as the induction dose in the phase III study. Phase III exposure-response analyses for efficacy during induction showed statistically significant exposure-response relationships at Week 12 following 1,200 mg IV at Weeks 0, 4, and 8, in line with phase IIb results. Exposure-response analyses for maintenance demonstrated modest improvement in Week 52 efficacy when increasing the subcutaneous dose from 180 mg to 360 mg with largely overlapping confidence intervals. Exposure-response analyses for safety indicated no apparent exposure-dependent safety events over the induction or maintenance treatment. Based on these results, the recommended dosing regimen for risankizumab in UC patients is 1,200 mg IV at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneously at Week 12 and every 8 weeks thereafter., (© 2024 AbbVie Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: SBS is a rare and disabling condition. The standard management is based on diet optimization with parenteral supplementation. In addition, glucagon-like peptide-2 (GLP-2)analogs, have shown promising results as disease-modifying therapies for SBS., Areas Covered: Short bowel syndrome (SBS) is defined as a reduction in functional intestinal length to less than 200 cm, leading to intestinal failure (IF) leading to malnutrition and parenteral support dependency. This review discusses the current management of SBS-CIFpatients, the place of GLP-2 analog treatment in terms of efficacy, safety and availability, and the new perspectives opened by the use of enterohormones., Expert Opinion: Clinical trials and real-world experience demonstrated that Teduglutide   reduces dependence on parenteral support and has a place in the management of patients with SBS-CIF.  The use of Teduglutide should be discussed in patients stabilized after resection and its introduction requires the advice of an expert center capable of assessing the benefit-risk ratio. The complex, individualized management of SBS-C IF requires theexpertise of a specialized IF center which a multidisciplinary approach. The arrival of new treatments will call for new therapeutic strategies, and the question of how to introduce and monitor them will represent a new therapeutic challenge.

Rationale: The interstitial pneumonia (IP) linked to vedolizumab (VDZ) in patients with ulcerative colitis (UC) is rare. Prompt diagnosis and treatment can improve patient outcomes., Patient Concerns: A 39-year-old man with UC who received VDZ as sole therapy developed symptoms such as chest tightness, cough, and suffocation., Diagnoses: IP was confirmed through pulmonary function tests, chest computed tomography, and bronchoscopic biopsy., Interventions: The patient was given methylprednisolone and VDZ cessation., Outcomes: The patient's symptoms improved and remained symptom-free after nearly 2 years., Lessons: VDZ-induced IP should be considered when evaluating pulmonary infections in UC patients treated with VDZ., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Teduglutide is a glucagon-like-peptide-2 analogue that reduces the need for parenteral support in patients with short bowel syndrome (SBS). Nevertheless, data about long-term therapy with teduglutide in children are still scarce. Our objective was to describe the real-life experience with teduglutide in children with SBS over the last 5 years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3 months. The data included demographic characteristics, medical background, anthropometric data, laboratory assessments, adverse events, and parenteral nutrition (PN) requirements. Treatment response was defined as a > 20% reduction in the PN requirement. The data were collected from the Research Electronic Data Capture (REDCap) database. Thirty-one patients from seven centres were included; the median age at the beginning of the treatment was 2.3 (interquartile range (IQR) 1.4-4.4) years; and 65% of the patients were males. The most frequent cause of IF was SBS (94%). The most common cause of SBS was necrotizing enterocolitis (35%). The median residual bowel length was 29 (IQR 12-40) cm. The median duration of teduglutide therapy was 19 (IQR 12-36) months, with 23 patients (74%) treated for > 1 year and 9 treated for > 3 years. The response to treatment was analysed in 30 patients. Twenty-four patients (80%) had a reduction in their weekly PN energy > 20% and 23 patients (77%) had a reduction in their weekly PN volume > 20%. Among the responders, 9 patients (29%) were weaned off PN, with a median treatment duration of 6 (IQR 4.5-22) months. The only statistically significant finding demonstrated an association between a > 20% reduction in the weekly PN volume and a younger age at the start of treatment (p = 0.028).   Conclusions: Teduglutide seems to be an effective and safe treatment for paediatric patients with IF. Some patients require a prolonged duration of treatment to achieve enteral autonomy. Starting treatment with teduglutide at a young age is associated with a higher response rate. What is Known: •  Glucagon-like peptide-2 (GLP-2) plays a crucial role in the regulation of intestinal adaptation in short bowel syndrome (SBS). Teduglutide is a GLP-2 analog that reduces the need for parenteral support in patients with SBS. • Data about long-term therapy with teduglutide in children in real life are still scarce. What is New: • Most pediatric patients with SBS respond in a satisfactory manner to teduglutide treatment. The occurrence of long-term adverse effects is exceptional. • Starting treatment with the drug at a young age is associated with a greater response rate., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mirikizumab is a humanized anti-interleukin-23p19 monoclonal antibody being developed for ulcerative colitis (UC) and Crohn's disease. We characterized the relationship of mirikizumab systemic exposure with efficacy and safety end points in patients with UC using phase II (NCT02589665) and III (NCT03518086, NCT03524092) trial data. Exposure-response models were developed for clinical remission, clinical response, endoscopic remission, and change in modified Mayo score following induction (50-1,000 mg i.v. every 4 weeks) and maintenance (200 mg s.c. every 4 or 12 weeks) treatment. These models evaluated observed and pharmacokinetic model-predicted mirikizumab exposures as the exposure measure. Key safety event rates were compared across mirikizumab exposure quartiles in the phase III trial. Mirikizumab efficacy in patients with UC showed an apparent positive association with systemic exposure following both induction and maintenance. However, further analysis found this relationship to be overstated by the presence of confounding factors that were not among the tested patient covariates. While prior biologic experience and baseline disease severity showed statistically significant influences on estimated placebo effect, no patient factors affected the mirikizumab effect parameters in any of the phase III exposure-response models. There was no apparent mirikizumab concentration relationship with any adverse event of special interest. When the phase II and III data and confounding are considered together, efficacy was unlikely to be strongly affected by variation in exposures across individual patients at the phase III dose. Together with the previously demonstrated mirikizumab exposure insensitivity to patient factors, these findings indicate that mirikizumab dose adjustment to patient characteristics is not required., (© 2024 Eli Lilly and Company. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Tumor necrosis factor-α inhibitors (TNFis) are used for the treatment of inflammatory bowel disease (IBD). The aim of this study was to evaluate the association between neurological adverse events (AEs) and TNFi use., Methods: Data of TNFis indicated for IBD were collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the marketed date to the second quarter of 2023. The reporting odds ratio (ROR) and a Bayesian confidence propagation neural network were used to identify signals., Results: A total of 4,964 neurological AEs were reported in the IBD population. Infliximab had 3 signals, including demyelination [ROR (95% CI): 1.69 (1.33,2.15)], meningitis listeria [ROR (95% CI): 5.05 (3.52,7.25)], and optic neuritis [ROR (95% CI): 1.72 (1.3,2.26)]. The signals for adalimumab were gait disturbance [ROR (95% CI): 1.43 (1.32,1.56)] and muscular weakness [ROR (95% CI): 1.4 (1.27,1.55)]. A peripheral neuropathy signal was found for adalimumab [ROR (95% CI): 1.34 (1.18,1.53)] and certolizumab pegol [ROR (95% CI): 1.49 (1.07,2.08)]. However, there were no signals among neurological AEs for golimumab., Conclusion: Neurological signals were detected for TNFi use, indicating that the risk of neurological AEs requires additional attention in clinical use of TNFis.