Intestinal fibrosis is an important complication of inflammatory bowel disease (IBD). In the course of the development of fibrosis, certain parts of the intestine become narrowed, significantly destroying the structure and function of the intestine and affecting the quality of life of patients. Chronic inflammation is an important initiating factor of fibrosis. Unfortunately, the existing anti-inflammatory drugs cannot effectively prevent and alleviate fibrosis, and there is no effective anti-fibrotic drug, which makes surgical treatment the mainstream treatment for intestinal fibrosis and stenosis. Mesenchymal stem cells (MSCs) are capable of tissue regeneration and repair through their self-differentiation, secretion of cytokines, and secretion of extracellular vesicles. MSCs have been shown to play an important therapeutic role in the fibrosis of many organs. However, the role of MSC in intestinal fibrosis largely remained unexplored. This review summarizes the mechanism of intestinal fibrosis, including the role of immune cells, TGF-β, and the gut microbiome and metabolites. Available treatment options for fibrosis, particularly, MSCs are also discussed.

• Fibrosis
• Humans
• Inflammatory Bowel Diseases/metabolism
• Intestines/pathology
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/metabolism
• Quality of Life

• Adalimumab
• Crohn’s disease
• Endoscopic recurrence
• Postoperative therapy

There are few reports of the efficacy of adalimumab (ADA) for clinical remission and preventing postoperative recurrence in Crohn's disease (CD) in Asian real practice settings. We conducted a Japanese multicenter retrospective observational study.

We evaluated patients with CD who were treated with ADA at 11 medical institutions in Japan to investigate the clinical efficacy of remission up to 52 weeks and the associated factors to achieve remission with a CD Activity Index (CDAI) < 150. The effects of preventing postoperative recurrence were also evaluated.

In 62 patients, the remission rates were 33.9, 74.2, 75.8, 77.4, and 66.1 % at 0, 4, 12, 26, and 52 weeks, respectively. Although 10 patients discontinued treatment due to primary nonresponse, secondary nonresponse, or adverse events, the ongoing treatment rate at 52 weeks was 83.9 %. Comparison of remission and non-remission on univariate analysis identified colonic type and baseline CDAI value as significant associated factors (P < 0.05). In 16 patients who received ADA to prevent postoperative recurrence, the clinical remission maintenance rate was 93.8 % and the mucosal healing rate was 64.3 % during a mean postoperative follow-up period of 32.3 months.

ADA effectively induced remission and prevented postoperative recurrence in patients with CD in a real practice setting.

• Adalimumab
• Crohn’s disease
• Japanese patients
• Preventing postoperative recurrence
• Real practice

• CDAI
• CDEIS
• CT-enterography
• Crohn’s disease
• MR-enterography
• MaRIA
• SES-CD
• disease activity
• therapeutic monitoring

• Crohn disease
• Recurrence
• Tumor necrosis factor-alpha

Endoscopic and clinical recurrence of Crohn’s disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

• Inflammatory bowel disease
• Crohn’s disease
• Postoperative recurrence
• Medical treatment
• Biologics

• Anti-Bacterial Agents/economics
• Anti-Bacterial Agents/therapeutic use
• Anti-Inflammatory Agents/economics
• Anti-Inflammatory Agents/therapeutic use
• Cost-Benefit Analysis
• Crohn Disease/diagnosis
• Crohn Disease/economics
• Crohn Disease/surgery
• Digestive System Surgical Procedures/adverse effects
• Digestive System Surgical Procedures/economics
• Drug Costs
• Endoscopy, Gastrointestinal
• Gastrointestinal Agents/economics
• Gastrointestinal Agents/therapeutic use
• Humans
• Patient Selection
• Predictive Value of Tests
• Risk Assessment
• Risk Factors
• Secondary Prevention
• Time Factors
• Treatment Outcome

AIM: To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn’s disease in high-risk patients.

METHODS: A multicenter, prospective, observational study was conducted from June 2009 until June 2010. We consecutively included high-risk Crohn’s disease patients who had undergone an ileal/ileocolonic resection. High-risk patients were defined as two or more criteria: smokers, penetrating pattern, one or more previous surgical resections or prior extensive resection. Subcutaneous adalimumab was administered 2 wk (± 5 d) after surgery at a dose of 40 mg eow, with an initial induction dose of 160/80 mg at weeks 0 and 2. Demographic data, previous and concomitant treatments (antibiotics, 5-aminosalicylates, corticosteroids, immunomodulators or biologic therapies), smoking status at the time of diagnosis and after the index operation and number of previous resections (type and reason for surgery) were all recorded. Biological status was assessed with C-reactive protein, erythrocyte sedimentation rate and fecal calprotectin. One year (± 3 mo) after surgery, an ileocolonoscopy and/or magnetic resonance enterography was performed. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. Morphological recurrence was based on magnetic resonance (MR) score ≥ MR1.

RESULTS: Twenty-nine patients (55.2% males, 48.3% smokers at diagnosis and 13.8% after the index operation), mean age 42.3 years and mean duration of the disease 13.8 years were included in the study. A mean of 1.76 (range: 1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection. 51.7% had previously received infliximab. Immunomodulators were given concomitantly to 17.2% of patients. Four of the 29 (13.7%) developed clinical recurrence, 6/29 (20.7%) endoscopic recurrence and 7/19 (36.8%) morphological recurrence after 1-year. All patients with clinical recurrence showed endoscopic and morphological recurrence. A high degree of concordance was found between clinical-endoscopic recurrence (κ = 0.76, P < 0.001) and clinical-morphological recurrence (κ = 0.63, P = 0.003). Correlation between endoscopic and radiological findings was good (comparing the 5-point Rutgeerts score with the 4-point MR score, a score of i4 was classified as MR3, i3 as MR2, and i2-i1 as MR1) (P < 0.001, r_s = 0.825). During follow-up, five (17.2%) patients needed adalimumab dose intensification (40 mg/wk); Mean time to intensification after the introduction of adalimumab treatment was 8 mo (range: 5 to 11 mo). In three cases (10.3%), a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk. One patient suffered an adverse event.

CONCLUSION: Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

• Crohn’s disease
• Postoperative recurrence
• Prevention
• Tumor necrosis factor alpha agents
• Adalimumab