Are proton‑pump inhibitors (PPIs) used to treat colitis?

Are PPIs Used in Colitis?

Proton pump inhibitors are used in specific forms of colitis, but their role varies dramatically by disease type: they are first-line therapy for mild oesophageal Crohn's disease, but observational evidence suggests they may worsen outcomes in ulcerative colitis and are associated with increased risk of microscopic colitis.

PPIs in Crohn's Disease (Upper GI Involvement)

For mild oesophageal Crohn's disease, PPIs are recommended as first-line medical therapy. 1

• The British Society of Gastroenterology recommends PPIs for mild oesophageal Crohn's disease, with escalation to corticosteroids if symptoms worsen and early anti-TNF therapy for moderate-to-severe disease. 1
• In upper gastrointestinal Crohn's disease without stenosis, PPIs are first-line therapy, followed by steroids as second-line and thiopurines/infliximab as third-line. 1
• Nutritional assessment and support is essential in all patients with oesophageal Crohn's disease. 1

PPIs and Ulcerative Colitis: Emerging Safety Concerns

Recent large-scale observational data suggest that PPI use in ulcerative colitis patients is associated with worse disease outcomes and should be used cautiously.

• In a Norwegian cohort of 10,149 newly diagnosed UC patients, PPI use independently increased the risk of starting advanced therapies (HR 1.54,95% CI 1.36-1.73), starting systemic glucocorticoids (HR 1.20,95% CI 1.07-1.34), and undergoing colectomy (HR 1.52,95% CI 1.17-1.98). 2
• Patients with UC using PPIs are less likely to achieve remission. 3
• The mechanism may involve PPI-induced alteration of the gut microbiome, which plays a role in UC pathogenesis. 2

PPIs and Microscopic Colitis: A Possible Association

PPIs are associated with increased risk of microscopic colitis, including both collagenous and lymphocytic subtypes.

• A systematic review of 19 publications found a possible association between PPIs and microscopic colitis development. 4
• Meta-analysis demonstrated significant associations between PPI exposure and collagenous colitis (OR 4.73,95% CI 1.99-11.22) and lymphocytic colitis (OR 3.77,95% CI 2.91-4.87). 5
• All studies were limited by small sample sizes and did not investigate dose-response relationships or differences between specific PPI agents. 4

PPIs and IBD Risk: Population-Level Evidence

Large population studies suggest PPI use is associated with increased risk of developing inflammatory bowel disease, though causality remains uncertain.

• In a U.S. population-based study of 45.5 million individuals, PPI users had increased odds of ulcerative colitis (OR 2.02,95% CI 1.98-2.06) and Crohn's disease (OR 2.79,95% CI 2.75-2.84) even after adjusting for NSAID use, smoking, alcoholism, GERD, IBS, and metabolic syndrome. 3
• A Canadian study found persons with IBD had higher rates of PPI use preceding their diagnosis, with Crohn's disease patients (RR 4.2,95% CI 3.7-4.6) more likely to be PPI users than ulcerative colitis patients (RR 2.4,95% CI 2.2-2.7). 6
• Meta-analysis of observational studies showed significantly higher risk of IBD with PPI use (adjusted OR 2.43,95% CI 1.18-5.02). 5

Clinical Algorithm for PPI Use in Colitis Patients

When to Use PPIs:

1. Oesophageal Crohn's disease (mild): Initiate PPI as first-line therapy 1
2. Upper GI Crohn's disease without stenosis: Use PPI as first-line 1
3. Eosinophilic oesophagitis: Omeprazole 20 mg twice daily for 8-12 weeks 7

When to Avoid or Use Cautiously:

1. Ulcerative colitis: Avoid unnecessary PPI use; if required for valid indication (e.g., GERD, GI bleeding prophylaxis), use lowest effective dose and monitor disease activity closely 2
2. Microscopic colitis: Consider PPI as potential causative agent; discontinue if no compelling indication 4
3. Patients at risk for IBD: Limit unnecessary PPI prescriptions 3

Important Caveats

• The association between PPIs and IBD development/worsening is based on observational data and cannot establish causality—residual confounding and reverse causation (treating early IBD symptoms with PPIs) remain possible explanations. 4, 3, 6
• When PPIs are indicated for valid reasons (e.g., GI bleeding prophylaxis in patients on anticoagulants/antiplatelets, severe GERD), the benefits typically outweigh the potential IBD-related risks. 7
• Fecal calprotectin interpretation is compromised in patients taking PPIs—a 3-week washout is required before using calprotectin to assess IBD activity, as PPIs independently elevate this biomarker through microbiome alterations. 7
• Clinicians should routinely question whether IBD patients are receiving unnecessary PPI treatment and discontinue therapy where appropriate, given the potential for worse disease outcomes. 4, 2