Prevention and Treatment of Stricturing Crohn’s Disease – Perspectives and Challenges

Sleiman, Joseph; Ouali, Sara El; Qazi, Taha; Cohen, Benjamin L.; Steele, Scott R.; Baker, Mark E.; Rieder, Florian

doi:10.1080/17474124.2021.1854732

Cited by 29 publications

(22 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gut microbiota is an indispensable driver in intestinal fibrogenesis. 1 , 33 , 34 Becker et al 35 found that Bacteroides fragilis , a gram-negative commensal of the phylum Bacteroidetes , was associated with stricturing disease behavior and severe disease activity in CD patients. However, a deeper understanding of B. fragilis in CD fibrosis needs to be clarified in further investigations.…”

Section: Search Strategymentioning

confidence: 99%

“… 72 Immunosuppressants and biological agents have no direct effect on fibrosis, although these are associated with a 96% and 94% reduction of stricture development, respectively. 1 , 73 …”

Section: Search Strategymentioning

confidence: 99%

“…CD patients refractory to medical or endoscopic treatment, or with complex complications (strictures, abscesses, and fistulae), would eventually need surgical interventions such as strictureplasty (SXP) and bowel resection. 1 , 92 Bislenghi et al 93 conducted a meta-analysis including 26 studies aiming to explore the efficacy of conventional (short and intermediate procedures such as Heineke–Mikulicz and Finney) and nonconventional (long entero-enterostomies such as Michelassi) SXP. Results showed a comparatively low rate of postoperative complications (15.5% versus 19.2%) and surgical recurrence (26.9% versus 18.2%) for the two types of surgical therapies during median follow-up periods of 65.3 and 96.3 months, respectively, suggesting that both techniques were feasible.…”

Section: Search Strategymentioning

confidence: 99%

“…Crohn’s disease (CD) is a chronic relapsing and remitting inflammatory disorder involving the whole gastrointestinal tract. 1 Approximately 70% of CD patients will develop stricturing or penetrating complications after 10 years of CD diagnosis. 2 A real-world study found that CD patients with fibrostenosis were at significantly higher risk for hospitalization, steroid dependency, repeated endoscopy, and surgery, as well as higher healthcare costs, compared with CD patients without fibrostenosis.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Intestinal strictures in Crohn’s disease: a 2021 update

Lin

Wang

Liu

et al. 2022

Therap Adv Gastroenterol

View full text Add to dashboard Cite

Intestinal strictures remain one of the most intractable and common complications of Crohn’s disease (CD). Approximately 70% of CD patients will develop fibrotic strictures after 10 years of CD diagnosis. Since specific antifibrotic therapies are unavailable, endoscopic balloon dilation and surgery remain the mainstay treatments despite a high recurrence rate. Besides, there are no reliable methods for accurately evaluating intestinal fibrosis. This is largely due to the fact that the mechanisms of initiation and propagation of intestinal fibrosis are poorly understood. There is growing evidence implying that the pathogenesis of stricturing CD involves the intricate interplay of factors including aberrant immune and nonimmune responses, host-microbiome dysbiosis, and genetic susceptibility. Currently, the progress on intestinal strictures has been fueled by the advent of novel techniques, such as single-cell sequencing, multi-omics, and artificial intelligence. Here, we perform a timely and comprehensive review of the substantial advances in intestinal strictures in 2021, aiming to provide prompt information regarding fibrosis and set the stage for the improvement of diagnosis, treatment, and prognosis of intestinal strictures.

show abstract

Section: Search Strategymentioning

confidence: 99%

“… 72 Immunosuppressants and biological agents have no direct effect on fibrosis, although these are associated with a 96% and 94% reduction of stricture development, respectively. 1 , 73 …”

Section: Search Strategymentioning

confidence: 99%

Section: Search Strategymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intestinal strictures in Crohn’s disease: a 2021 update

Lin

Wang

Liu

et al. 2022

Therap Adv Gastroenterol

View full text Add to dashboard Cite

show abstract

“…Currently, the therapies for CD are broadly anti-inflammatory, such as immunomodulators and anti-TNFα immunotherapies, and directed largely against immune cells 5 . However, these have only limited effects on stricturing, typically decreasing or slowing stricture formation without preventing occurrence and most patients still progress to require surgery; the other newer biological therapies have not yet shown effect against stricturing disease 6 . This emphasizes the need for identification of cellular mechanisms that contribute to stricture formation as well as the ability to selectively target these processes in the inflamed region (reviewed 7 ).…”

Section: Introductionmentioning

confidence: 99%

Nintedanib regulates intestinal smooth muscle hyperplasia and phenotype in vitro and in TNBS colitis in vivo

Kataria

Kerr

Lourenssen

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Chronic inflammation of the human intestine in Crohn’s disease (CD) causes bowel wall thickening, which typically progresses to stricturing and a recurrent need for surgery. Current therapies have limited success and CD remains idiopathic and incurable. Recent evidence shows a key role of intestinal smooth muscle cell (ISMC) hyperplasia in stricturing, which is not targeted by current anti-inflammatory therapeutics. However, progression of idiopathic pulmonary fibrosis, resembling CD in pathophysiology, is controlled by the tyrosine kinase inhibitors nintedanib (NIN) or pirfenidone, and we investigated these drugs for their effect on ISMC. In a culture model of rat ISMC, NIN inhibited serum- and PDGF-BB-stimulated growth and cell migration, and promoted the differentiated phenotype, while increasing secreted collagen. NIN did not affect signaling through PDGF-Rβ or NFκB but did inhibit cytokine-induced expression of the pro-inflammatory cytokines IL-1β and TNFα, supporting a transcriptional level of control. In TNBS-induced colitis in mice, which resembles CD, NIN decreased ISMC hyperplasia as well as expression of TNFα and IL-1β, without effect in control animals. NIN also inhibited growth of human ISMC in response to human serum or PDGF-BB, which further establishes a broad range of actions of NIN that support further trial in human IBD.

show abstract

Validation of stricture length, duration and obstructive symptoms as predictors for intervention in ileal stricturing Crohn's disease

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background Risk factors for intervention in terminal ileal (TI) stricturing Crohn's disease (CD) are poorly defined. Novel and rigorous definitions for TI strictures recently became available. Objective We aimed to describe the rates of symptoms or need for endoscopic balloon dilation (EBD) or surgery as well as risk factors of progression in a well‐defined stricturing CD cohort. Methods Consecutive adult patients with non‐penetrating stricturing TI CD, as defined by centrally‐read magnetic resonance enterography CONSTRICT criteria, were separated into a derivation and validation cohort. Clinical and imaging characteristics were collected following prespecified scoring conventions. Primary outcome was a composite endpoint of EBD or surgery (“intervention”). Multivariable analysis was performed. Results Eighty‐six patients (48.8% female, median age 36 years) met selection criteria, 17.4% had prior EBD, 59.3% previously received biologics and 58.1% of strictures were anastomotic. Median follow‐up was 63.4 [95% CI: 57, 68.9] months. In the derivation cohort, at 12 and 48 months, 26% and 45% of patients had intervention, respectively. Multivariable analysis showed obstructive symptoms (Hazard ratio [HR] 1.444; 95% CI 1.126–1.852), stricture duration (HR 0.974; 95% CI, 0.954–0.995) and length (HR 1.039; 95% CI, 1.011–1.069) predicted intervention. The concordance index for split‐sample validation was 0.74 and 0.67, respectively. Biologics were not associated with intervention. An online risk calculator was constructed. Conclusion In patients with TI stricturing CD, 26% and 45% required intervention at 1 and 4 years. Obstructive symptoms, stricture duration and length were independent and validated predictors of the need for intervention. These findings are important for clinical practice and aid in the design of future trials for CD strictures.

show abstract

Prevention and Treatment of Stricturing Crohn’s Disease – Perspectives and Challenges

Cited by 29 publications

References 125 publications

Intestinal strictures in Crohn’s disease: a 2021 update

Intestinal strictures in Crohn’s disease: a 2021 update

Nintedanib regulates intestinal smooth muscle hyperplasia and phenotype in vitro and in TNBS colitis in vivo

Validation of stricture length, duration and obstructive symptoms as predictors for intervention in ileal stricturing Crohn's disease

Contact Info

Product

Resources

About