Effectiveness of Mesalazine, Thiopurines and Tumour Necrosis Factor Antagonists in Preventing Post-Operative Crohn's Disease Recurrence in a Real-Life Setting

Allocca, Mariangela; Landi, Rosario; Bonovas, Stefanos; Fiorino, Gionata; Papa, Alfredo; Spinelli, Antonino; Furfaro, Federica; Peyrin–Biroulet, Laurent; Armuzzi, Alessandro; Danese, Silvio

doi:10.1159/000480231

Cited by 17 publications

(8 citation statements)

References 31 publications

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“…It is possible that mesalamine is less likely to impact the small-intestinal microbiota compared to the large intestine; indeed, mesalamine is historically known to have a lower efficacy in treating Crohn’s disease, which manifests in the small intestine, compared to ulcerative colitis, which manifests in the large intestine (22, 48, 49). As indicated by the variability of mesalamine in the subjects in this study, the effects of mesalamine on the small-intestinal microbiota may be highly individualized (24, 50–52). Furthermore, individuals with disease may harbor a distinct microbiota that responds to mesalamine differently.…”

Section: Discussionmentioning

confidence: 93%

Spatial and Temporal Analysis of the Stomach and Small-Intestinal Microbiota in Fasted Healthy Humans

Seekatz

Schnizlein

Koenigsknecht

et al. 2019

mSphere

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Although the microbiota in the proximal gastrointestinal (GI) tract have been implicated in health and disease, much about these microbes remains understudied compared to those in the distal GI tract. This study characterized the microbiota across multiple proximal GI sites over time in healthy individuals. As part of a study of the pharmacokinetics of oral mesalamine administration, healthy, fasted volunteers (n = 8; 10 observation periods total) were orally intubated with a four-lumen catheter with multiple aspiration ports. Samples were taken from stomach, duodenal, and multiple jejunal sites, sampling hourly (≤7 h) to measure mesalamine (administered att = 0), pH, and 16S rRNA gene-based composition. We observed a predominance ofFirmicutesacross proximal GI sites, with significant variation compared to stool. The microbiota was more similar within individuals over time than between subjects, with the fecal microbiota being unique from that of the small intestine. The stomach and duodenal microbiota displayed highest intraindividual variability compared to jejunal sites, which were more stable across time. We observed significant correlations in the duodenal microbial composition with changes in pH; linear mixed models identified positive correlations with multipleStreptococcusoperational taxonomic units (OTUs) and negative correlations with multiplePrevotellaandPasteurellaceaeOTUs. Few OTUs correlated with mesalamine concentration. The stomach and duodenal microbiota exhibited greater compositional dynamics than the jejunum. Short-term fluctuations in the duodenal microbiota were correlated with pH. Given the unique characteristics and dynamics of the proximal GI tract microbiota, it is important to consider these local environments in health and disease states.IMPORTANCEThe gut microbiota are linked to a variety of gastrointestinal diseases, including inflammatory bowel disease. Despite this importance, microbiota dynamics in the upper gastrointestinal tract are understudied. Our article seeks to understand what factors impact microbiota dynamics in the healthy human upper gut. We found that the upper gastrointestinal tract contains consistently prevalent bacterial OTUs that dominate the overall community. Microbiota variability is highest in the stomach and duodenum and correlates with pH.

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Section: Discussionmentioning

confidence: 93%

Spatial and Temporal Analysis of the Stomach and Small-Intestinal Microbiota in Fasted Healthy Humans

Seekatz

Schnizlein

Koenigsknecht

et al. 2019

mSphere

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“…Altogether 87 articles were selected for detailed evaluation, among which 24 articles were included (Figure 1). Generally, articles originated from Europe, 21‐36 Japan, 28,37‐41 the United States 42,43 and Oceania, 44 comprising 11 RCTs, 23,26,29,32,34,36,38,39,41,43,44 and 13 cohort or case‐control studies 21,22,24,25,27,28,30,31,33,35,37,40,42 . Most of the articles prescribed anti‐TNF‐α therapy, either with infliximab or adalimumab, with one article using vedolizumab.…”

Section: Resultsmentioning

confidence: 99%

Quantifying the rate of recurrence of postoperative Crohn's disease with biological therapy. A meta‐analysis

Jain

Chin

et al. 2021

J of Digest Diseases

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Objective Preventing the postoperative recurrence (POR) of Crohn's disease (CD) poses a significant challenge to clinicians. With the advent of biologics, various studies have observed a reduction of recurrence after surgery. Hence, we performed a systematic review and meta‐analysis to identify the rate of POR at different time points in the era of biologic use. Methods We performed a literature search using Medline and Embase databases for studies investigating biologics in preventing the POR of CD. Data were extracted, and a single‐arm meta‐analysis with generalized linear mixed model and Clopper‐Pearson method for confidence interval (CI) was performed to identify endoscopic, clinical and surgical recurrence rates at 6 months and 1, 2 and 5 years postoperatively. Results Altogether 24 studies were included in the meta‐analysis. The endoscopic, clinical and surgical POR rate with the use of anti‐tumor necrosis factor (TNF)‐α agents at 1 year was 21.72% (95% CI 16.28%‐28.37%), 13.06% (95% CI 8.18%‐18.92%) and 3.76% (95% CI 1.37%‐9.91%), respectively. The 5‐year recurrence rate was 84.21% (95% CI 72.35%‐91.57%) and 17.49% (95% CI 9.17%‐30.80%) for endoscopic and surgical recurrence, respectively. Subgroup analyses at 1 year for the type of anti‐TNF‐α agent or the timing of initiation after surgery showed no significant difference in endoscopic, clinical and surgical recurrence rates. Conclusions Anti‐TNF‐α agents are effective at preventing clinical, endoscopic and surgical POR of CD. The timing of initiating biological therapy after surgery has no significant effect on the rate of POR. The efficacy of infliximab and adalimumab for postoperative recurrence prevention is similar.

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“…In addition, while many studies have investigated immunosuppressants after index ileocaecal resection, limited evidence is available on the optimal immunosuppressive regimen in CD patients with refractory disease who require recurrent surgery. Moreover, trials that evaluate anti‐TNF therapy tend to be focused on endoscopic rather than surgical recurrence .…”

Section: Discussionmentioning

confidence: 99%

Mesenteric granulomas independently predict long‐term risk of surgical recurrence in Crohn's disease

et al. 2019

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Aim The risk factors that predict surgical recurrence in Crohn's disease (CD) remain controversial. Postoperative anti-tumour necrosis factor (anti-TNF) therapy might lower recurrence rates whilst the presence of mesenteric granulomas has been postulated to increase the risk. We hypothesized that mesenteric granulomas indicate disease severity and might predict the risk of surgical recurrence, irrespective of immunosuppressive therapy.Method We performed a retrospective review of all consecutive patients undergoing operations for CD between January 2000 and December 2014 at a single tertiary referral centre and assessed the perioperative factors and histological findings at the time of surgery. Surgical recurrence rates and the immunosuppressive regimen were assessed through retrospective chart review and telephone interviews.Results A total of 274 patients were eligible for analysis. Median follow-up was 8.54 (5.48-14.42) years. A total of 63 patients (23.0%) underwent surgery for recurrent CD after a median of 4.75 (2.10-7.96) years. In final histology, 35 (12.8%) patients had mesenteric granulomas. TNF inhibitors were administered postoperatively in 104 (38.0%) and thiopurines in 137 (50.0%) patients. In univariate analysis, only the presence of mesenteric granulomas [hazard ratio (HR) 1.95; 95% CI 1.05-3.62; P = 0.035] significantly increased the risk for recurrent surgery while postoperative anti-TNF (HR 0.85; 95% CI 0.49-1.50; P = 0.581) or thiopurine therapy (HR 1.03; 95% CI 0.61-1.73; P = 0.916) did not. In multivariate analysis, only the presence of mesenteric granulomas significantly influenced the risk of surgical recurrence (HR 1.94, 95% CI 1.04-3.60; P = 0.037).Conclusion Intestinal and mesenteric granulomas should be differentiated in pathology reports, because mesenteric, but not intestinal, granulomas may be associated with an increased risk of surgical recurrence.Keywords Inflammatory bowel disease, laparoscopy, intestinal resectionWhat does this paper add to the literature? This paper investigated several established, as well as recently suggested, risk factors for surgical recurrence of Crohn's disease in a large single-centre long-term retrospective review. It shows that mesenteric granulomas are an independent risk factor for surgical recurrence while postoperative immunosuppression did not alter the risk of recurrence.

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Effectiveness of Mesalazine, Thiopurines and Tumour Necrosis Factor Antagonists in Preventing Post-Operative Crohn's Disease Recurrence in a Real-Life Setting

Cited by 17 publications

References 31 publications

Spatial and Temporal Analysis of the Stomach and Small-Intestinal Microbiota in Fasted Healthy Humans

Spatial and Temporal Analysis of the Stomach and Small-Intestinal Microbiota in Fasted Healthy Humans

Quantifying the rate of recurrence of postoperative Crohn's disease with biological therapy. A meta‐analysis

Mesenteric granulomas independently predict long‐term risk of surgical recurrence in Crohn's disease

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