# Pharmacological management of upper gastrointestinal Crohn’s disease: a systematic review

## TL;DR

This review finds limited evidence on treating upper gastrointestinal Crohn’s disease, with some benefits from corticosteroids and anti-TNF drugs.

## Contribution

A systematic review of pharmacological interventions for upper gastrointestinal Crohn’s disease, highlighting gaps in evidence-based treatment strategies.

## Key findings

- Anti-TNF drugs and corticosteroids showed clinical improvements in UGICD, but evidence is limited to observational studies.
- Few studies reported on advanced therapies like anti-integrins and anti-interleukin12/23, with minimal evidence of effectiveness.
- Only 8.5% of patients in the studies had isolated UGICD, indicating most had overlapping ileocolonic disease.

## Abstract

Upper gastrointestinal Crohn’s disease (UGICD) is an uncommon phenotype with limited management guidelines. We reviewed evidence on the safety and efficacy of pharmacological interventions for UGICD.

We searched MEDLINE, Embase, and Cochrane CENTRAL (1990-2025) for randomized controlled trials (RCTs) and comparative observational studies evaluating pharmacological or dietary interventions for UGICD, including esophagus to jejunum. Two reviewers screened studies, extracted data, and assessed bias (Newcastle–Ottawa Scale). Primary outcomes were clinical remission and response. Due to limited, heterogeneous evidence, data are summarized descriptively.

Of 1207 citations, 11 observational studies (nine retrospective, two prospective) and post-hoc analyses from two RCTs met the criteria, involving 387 patients. Most had ileocolonic involvement (280/387; 72.3%); only 8.5% (33/387) had isolated UGICD. Five studies (137 patients) reported esophageal CD. Follow-up ranged from 6 weeks to 28 years. Interventions and outcomes varied. Anti-tumor necrosis factor (anti-TNF) drugs and corticosteroids, alone or combined with other treatments, were associated with improvements in clinical outcomes, endoscopic healing, and histology, but controlled data are lacking. Other therapies, including proton pump inhibitors, H2-receptor antagonists, enteric nutrition, immunomodulators, anti-integrins, and anti-interleukin12/23, showed moderate to minimal improvement.

Our systematic review highlights a paucity of evidence to inform therapeutic strategies in UGICD. Positive outcomes were reported for corticosteroids and anti-TNF, but from small observational and uncontrolled studies. Data for most advanced therapies remain limited, highlighting a large unmet need to inform clinical practice.

Graphical Abstract