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.

Figure 1.

PRISMA flow chart search strategy for systemic medical stricture therapy for small bowel Crohn’s Disease strictures. *Records excluded as review articles, editorials, case reports, Non-Crohn’s disease, book chapters, abstracts, non-English articles. **Records excluded for reasons including: steroid injection (5), pediatric population (4), balloon dilation (7), efficacy of single balloon enteroscopy (1), enteral nutrition (2), tuberculosis medication as intervention (1), absent stricture (post resection) (6), endpoints not specified (2), non-small bowel stricture (19).

Figure 2.

PRISMA flow chart search strategy for endoscopic intralesional medication injection for small bowel Crohn’s Disease strictures. *Records excluded as review articles, case reports, Non-Crohn’s disease, book chapters, abstracts, non-English articles. **Records excluded for reasons including: non-small bowel stricture (pylorus, esophageal, colon, rectum, pouch) (7), pediatric population (2), no use of intralesional therapies after EBD (1), review article (2), peristomal pyoderma gangrenosum (1), ulcerative colitis stricture (1), bowel stent insertion (2).

Figure 3.

Forest Plot for studies reporting on surgical rate of small bowel Crohn’s disease strictures treated with systemic agents. Random effects model demonstrating a pooled event rate for surgical resection of 27.6% (95% CI: 18.4%−39.3%; I² 75%, t² 56.3%) over a median follow up time of 23 months (range 5.5–105.8). *Randomized controlled trial and only study not involving biologic agents.

Figure 4.

Forest Plot for studies reporting on surgical rate of small bowel Crohn’s disease strictures treated with intralesional medications post endoscopic balloon dilation. Random effects model demonstrating a pooled event rate for surgical resection 18.5% (95% CI: 8.3–36.2%, I²: 62%, t² 58.2%) over a median follow up time of 21.8 months (range 5–47). *intralesional infliximab, all other studies utilized intralesional corticosteroids.

Figure 5.

Forest Plot for studies reporting on repeat endoscopic balloon dilation of small bowel Crohn’s disease strictures treated intralesional agents. Random effects model demonstrating a pooled event rate for balloon dilation of 58.3% (95% CI: 36.3%−77.3%; I²: 59%, t² 71.3%) over a median follow up of 21.8 months (range 5–47). *Randomized controlled trial.