Systematic review: medical therapy for fibrostenosing Crohn’s disease

Abstract

Background: Medical therapy and/or endoscopic balloon dilation with intralesional therapies are options for the treatment of small bowel fibrostenotic Crohn's disease (CD). Aim: To perform a systematic review summarising evidence for efficacy of systemic and endoscopic intralesional medical therapy in established small bowel strictures in adult CD patients. Methods: A systematic search of MEDLINE, EMBASE, CENTRAL and Scopus was conducted. Primary outcomes were rates of surgical resection and repeat endoscopic dilation. Pooled event rates from random effects models across studies with 95% confidence intervals were reported.Results: Ten studies describing systemic medical therapy and eight studies of intralesional injection were included. One randomised controlled trial each for systemic therapy and intrastricture injection were identified. Only observational studies were found for systemic biologic therapies, which exclusively included tumour necrosis factor (TNF) antagonists, while intralesional therapies all involved corticosteroids except for one study that evaluated infliximab. Pooled event rates for surgical resection after systemic and intralesional therapy were 28.3% (95% CI: 18.2%-41.3%) and 18.5% (95% CI: 8.3%-36.2%), respectively over a median follow-up of 23 months (range 5.5-105.8), and 21.8 months (range 5-47). Risk of repeat endoscopic balloon dilation in those with intralesional therapy was 58.3% (95% CI: 36.6%-77.3%) over a median follow-up of 21.8 months (range 5-47). Conclusions:There are no favoured therapies for patients with stricturing small bowel CD. Data are lacking for ustekinumab and vedolizumab. No endoscopic intralesional medications provided a clear benefit for prevention of repeat EBD or surgery.

Crohn’s strictures open with anti-mycobacterial antibiotic therapy: A retrospective review

“…This may in part be explained by the reported anti-MAP activity of cytostatic agents, but this has not previously been reported in cases of stricturing CD[ 29 , 30 ]. Notably this correlation was not found with biologic therapy, which has been described to decrease both the immunogenicity and intracellular survival of MAP, and alleviate strictures[ 10 - 12 , 31 ]. In our study, patient demographics, area of involvement, number of strictures, duration of treatment and clinical response were not significantly related to stricture outcome.…”

“…In our review, AMAT provided a high rate of stricture resolution (67%) compared with other therapies in the limited available literature. Recently, the Stricture Therapy and Research Consortium identified only ten studies involving stricture therapy, none of which included antibiotic therapy, and concede there is a need for RCTs into systemic medical therapies for CD strictures[ 10 ]. To date, the largest multicenter, prospective study (CREOLE), found adalimumab displayed efficacy in stricture success in 62/97 (64%) patients[ 11 ].…”

“…Added biological therapies and exclusive enteral nutrition (EEN) have shown promise in treating CD strictures, but alone are not effective in resolving them[ 10 - 14 ]. In other stenosing conditions such as bowel tuberculosis (TB), Helicobacter pylori ( H. pylori ) duodenal ulcer disease and β-hemolytic Streptococcus oesophagitis, antimicrobial treatment can achieve complete resolution of strictures.…”

Therapeutic Targeting of Intestinal Fibrosis in Crohn’s Disease

“…Subsequent management is dependent on strictures' inflammation degree and morphometrics, such as location and length, assessed by biomarkers (e.g., C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin), endoscopy, computed tomography, or magnetic resonance imaging. Current complications (such as phlegmon, abscess, dysplasia, or malignancy) and patient preferences should also be taken into account [5,54].…”

Early Laparoscopic Ileal Resection for Localized Ileocecal Crohn’s Disease: Hard Sell or a Revolutionary New Norm?

“…Moran et al [42] evaluated factors associated with failure of medical therapy: patients with stricturing or penetrating disease phenotypes had >6-and 3-fold increased risks of failing medical therapy and requiring surgical intervention. Indeed, very little evidence supports the use of biologic agents for resolving internal penetrating disease or for "cold" fibrostenotic strictures [43,44]. In these scenarios, as previously stated, delaying inevitable surgery by introducing a biologic agent may have detrimental consequences as it changes the benefit-risk proposition.…”