Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases

Ananthakrishnan, Ashwin N.; Luo, Chengwei; Yajnik, Vijay; Khalili, Hamed; Garber, John J.; Stevens, Betsy; Cleland, Thomas A.; Xavier, Ramnik J.

doi:10.1016/j.chom.2017.04.010

Cited by 316 publications

(263 citation statements)

References 51 publications

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“…Interestingly, in a subpopulation of patients with fistulising Crohn's disease who participated in the vedolizumab GEMINI 2 trial, prior failure of antibiotic therapy was a negative predictor of fistula closure . A recent study using a prospectively recruited cohort of patients with inflammatory bowel disease initiating vedolizumab investigated the relationship between gut microbiome at baseline and response to treatment . This study concluded that gut microbiome at baseline could be an indicator of clinical response .…”

Section: Discussionmentioning

confidence: 99%

“…A recent study using a prospectively recruited cohort of patients with inflammatory bowel disease initiating vedolizumab investigated the relationship between gut microbiome at baseline and response to treatment . This study concluded that gut microbiome at baseline could be an indicator of clinical response . Thus, a more diverse microbiome at baseline may reflect prevalent microbes and/or metabolites with anti‐inflammatory effect on colonic inflammation and a less disrupted mucosal barrier, associated with greater treatment response.…”

Section: Discussionmentioning

confidence: 99%

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Vedolizumab for perianal Crohn’s disease: a multicentre cohort study in 151 patients

Chapuis-Biron¹,

Bourrier²,

Nachury³

et al. 2020

Aliment Pharmacol Ther

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Summary Background The management of Crohn's disease patients with perianal lesions and anti‐TNF failure is challenging. Aims To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real‐life cohort. Methods We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. Results One hundred and fifty‐one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti‐TNF. The median follow‐up time was 52 weeks. Sixty‐eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04‐0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25‐18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. Conclusions We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vedolizumab for perianal Crohn’s disease: a multicentre cohort study in 151 patients

Chapuis-Biron¹,

Bourrier²,

Nachury³

et al. 2020

Aliment Pharmacol Ther

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“…In another study, sulfate‐reducing bacteria, which may proliferate with the release of toxic sulfide, were the dominant microflora in UC, but they were in fewer in healthy individuals ) . Thus, changes in the trajectory of early microbiome after treatment may be a marker of a therapeutic response to inflammatory bowel disease (IBD) . Dysbiosis in patients with UC is summarized in Table .…”

Section: Ecological Imbalance Of Intestinal Flora In Ucmentioning

confidence: 99%

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Guo

Liu

Hao

2020

J of Digest Diseases

145

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Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem—based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic‐associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.

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“…A recent proof-of-concept study that prospectively assessed fecal metagenomes from 85 IBD patients commencing vedolizumab found that responsive patients were characterized at baseline by higher abundance of butyrate producers such as Roseburia inulinivorans along with enrichment of particular microbial metabolic pathways including branched chain amino acid biosynthesis. 149 Further work is required to better define the likely crucial relationship between patient microbiota phenotype and responsiveness to biologic therapies.…”

Section: What Is On the Horizonmentioning

confidence: 99%

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

et al. 2018

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The emergence of biologic therapies is arguably the greatest therapeutic advance in the care of inflammatory bowel disease (IBD) to date, allowing directed treatments targeted at highly specific molecules shown to play critical roles in disease pathogenesis, with advantages in potency and selectivity. Furthermore, a large number of new biologic and small-molecule therapies in IBD targeting a variety of pathways are at various stages of development that should soon lead to a dramatic expansion in our therapeutic armamentarium. Additionally, since the initial introduction of biologics, there have been substantial advances in our understanding as to how biologics work, the practical realities of their administration, and how to enhance their efficacy and safety in the clinical setting. In this review, we will summarize the current state of the art for biological therapies in IBD, both in terms of agents available and their optimal use, as well as preview future advances in biologics and highly targeted small molecules in the IBD field.

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Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases

Cited by 316 publications

References 51 publications

Vedolizumab for perianal Crohn’s disease: a multicentre cohort study in 151 patients

Vedolizumab for perianal Crohn’s disease: a multicentre cohort study in 151 patients

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

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