Unmet needs in inflammatory bowel disease

Revés, Joana; Ungaro, Ryan C.; Torres, Joana

doi:10.1016/j.crphar.2021.100070

Cited by 17 publications

(9 citation statements)

References 76 publications

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“…IBD, a common chronic inflammatory disease, has received great attention in recent years with an increasing global incidence ( 28 , 29 ). Despite progress in its prevention, its impact continues to be being relevant, and new preventive strategies for IBD are needed ( 30 , 31 ). Several tryptophan metabolites have been identified to protect against inflammation caused by IBDs ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with IPA ameliorates colitis in mice: Colon transcriptome and fecal 16S amplicon profiling

Hou

et al. 2022

Front. Immunol.

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3-Indolepropionic acid (IPA) is a tryptophan metabolite that has anti-inflammatory properties. The present study try to investigate the phylactic effects of IPA on dextran sodium sulfate (DSS)-induced colitis mice. The results showed that IPA pretreatment ameliorated the DSS-induced decrease in growth performance, and intestinal damage and enhanced immunity in mice. RNA-seq analysis of mouse colon samples revealed that the differentially expressed genes (DEGs) were mainly enriched in immune-related pathways. 16S rRNA sequencing showed that IPA pretreatment ameliorated DSS-induced colonic microbiota dysbiosis. Moreover, the expression levels of gut immune genes were positively correlated with the relative abundance of several probiotics, such as Alloprevotella and Catenibacterium. In conclusion, IPA alleviates DSS-induced acute colitis in mice by regulating inflammatory cytokines, balancing the colonic microbiota and modulating the expression of genes related to inflammation, which would also provide a theoretical basis for IPA as a strategy to improve intestinal health.

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Section: Discussionmentioning

confidence: 99%

Pretreatment with IPA ameliorates colitis in mice: Colon transcriptome and fecal 16S amplicon profiling

Hou

et al. 2022

Front. Immunol.

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“…In this type of patient, the use of gut-selective immunosuppressants seems to have the potential to reduce the risk of adverse events, but further studies are needed. Finally, other settings requiring further data and advancements are relative to the use of novel non-invasive markers for monitoring the disease, with a better correlation with mucosal inflammation and disease progression, and the improved control of fatigue together with anxiety and depression which are able to affect greatly the disease course and therefore should be considered in its management ( 261 ).…”

Section: Unmet Needs In Ibdmentioning

confidence: 99%

Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease

et al. 2023

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Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.

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“…Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC), which are chronic inflammatory disorders of the gastrointestinal (GI) tract exhibiting unpredictable course of relapses and remission 1,2 . In 2019, there were approximately 4.9 million cases of IBD globally 3 .…”

Section: Introductionmentioning

confidence: 99%

Safety, tolerability, and pharmacokinetics of single‐ and multiple‐ascending doses of olamkicept: Results from randomized, placebo‐controlled, first‐in‐human phase I trials

Wagner,

Schreiber,

Bagger

et al. 2024

Clinical Translational Sci

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Olamkicept selectively inhibits the cytokine interleukin‐6 (IL‐6) trans‐signaling pathway without blocking the classic pathway and is a promising immunoregulatory therapy for inflammatory bowel disease (IBD). These first‐in‐human, randomized, placebo‐controlled, single‐ (SAD) and multiple‐ascending dose (MAD) trials evaluated olamkicept safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics. Doses tested in the SAD trial included seven single intravenous doses (0.75, 7.5, 75, 150, 300, 600, and 750 mg) and one subcutaneous (SC) dose (60 mg) given to healthy subjects (N = 64), and three intravenous doses (75 mg, 300 mg, and 750 mg) given to patients with Crohn's disease (CD; N = 24). Doses tested in the MAD trial included multiple intravenous doses (75, 300, and 600 mg once weekly for 4 weeks) given to healthy subjects (N = 24). No severe or serious treatment‐emergent adverse events (TEAEs) were recorded. The most common TEAEs were headache, nasopharyngitis, and myalgia in the SAD trial, and diarrhea, headache, and cough in the MAD trial. Infusion‐related reactions occurred in one and two subjects in the SAD and MAD trial, respectively, leading to treatment discontinuation in the MAD trial. Olamkicept showed dose‐independent pharmacokinetics after single and multiple administrations, and there was no major difference in systemic exposure between healthy subjects and patients with CD. Complete target engagement (inhibition of phosphorylation of signal transducer and activator of transcription‐3) was achieved in blood around or above olamkicept serum concentrations of 1–5 μg/mL. Overall, these results suggest that olamkicept is safe and well‐tolerated in healthy subjects and patients with CD after single intravenous/SC and multiple intravenous administrations.

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Unmet needs in inflammatory bowel disease

Cited by 17 publications

References 76 publications

Pretreatment with IPA ameliorates colitis in mice: Colon transcriptome and fecal 16S amplicon profiling

Pretreatment with IPA ameliorates colitis in mice: Colon transcriptome and fecal 16S amplicon profiling

Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease

Safety, tolerability, and pharmacokinetics of single‐ and multiple‐ascending doses of olamkicept: Results from randomized, placebo‐controlled, first‐in‐human phase I trials

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