How to manage persistent duodenal ulcers in patients on Proton Pump Inhibitor (PPI) therapy?

Management of Persistent Duodenal Ulcers on PPI Therapy

When duodenal ulcers persist despite standard PPI therapy, the priority is to verify and address H. pylori infection, optimize PPI dosing to twice-daily administration, exclude secondary causes of ulceration, and consider switching to potassium-competitive acid blockers (P-CABs) in true PPI failures. 1

Immediate Diagnostic Steps

Test for H. pylori Infection

• All patients with persistent duodenal ulcers must be tested for H. pylori, as this is the most common cause of treatment failure. 1
• Negative H. pylori tests obtained during acute bleeding or active PPI therapy should be repeated, as false negatives are common in these settings. 1
• If H. pylori is present, provide eradication therapy with confirmation of successful eradication 4-6 weeks post-treatment. 1, 2

Exclude Secondary Causes

• Rule out malignancy, particularly gastric cancer presenting as ulceration. 1
• Assess for opportunistic infections (CMV, HSV) in immunocompromised patients. 1
• Evaluate for vasculitis or ischemic ulceration. 1
• Consider Zollinger-Ellison syndrome if ulcers are multiple, refractory, or in unusual locations. 1

Optimize PPI Therapy

Increase PPI Dosing

• Switch from once-daily to twice-daily PPI dosing (e.g., omeprazole 40 mg twice daily or equivalent). 1
• For high-risk ulcers, twice-daily oral PPIs reduce rebleeding risk (RR 0.37) compared to once-daily dosing. 1
• Continue twice-daily dosing for 14 days, then transition to once-daily maintenance. 1

Address Absorption Issues

• Assess for delayed gastric emptying, which reduces PPI absorption and plasma levels. 3
• Consider switching from single-unit enteric-coated tablets (omeprazole) to multi-unit enteric-coated granules in capsules (lansoprazole), which may improve absorption in patients with gastroparesis. 3
• In patients with moderate gastroparesis, doubling the PPI dose may be necessary. 3

Verify Medication Adherence and Timing

• Confirm the patient is taking PPIs consistently. 4
• Standard PPI therapy for duodenal ulcers requires 2-4 weeks for healing, while gastric ulcers require 4-8 weeks. 4

Address Ulcerogenic Medications

NSAIDs and Antiplatelet Agents

• Discontinue NSAIDs if possible, as continued use is the second most common cause of persistent ulceration. 1
• If NSAIDs must be continued, switch to a COX-2 inhibitor plus PPI therapy, which provides superior protection compared to either agent alone. 1
• For patients requiring aspirin for cardiovascular prophylaxis, continue PPI co-therapy indefinitely. 1

Consider Alternative Acid Suppression

Potassium-Competitive Acid Blockers (P-CABs)

• P-CABs (vonoprazan, tegoprazan) may be useful in true PPI treatment failures, assuming secondary causes have been excluded. 1, 5
• Vonoprazan 20 mg daily demonstrated non-inferiority to lansoprazole 30 mg for duodenal ulcer healing (96% vs 98%). 1
• P-CABs provide more rapid and potent acid inhibition than PPIs, with less variability related to CYP2C19 polymorphisms. 1
• However, P-CABs should not be first-line therapy due to higher costs and limited long-term safety data. 1, 5

Treatment Duration

Standard Healing Course

• Continue PPI therapy for 6-8 weeks to allow complete mucosal healing. 1, 6
• After healing, long-term PPI is not recommended unless the patient has ongoing NSAID use or recurrent H. pylori infection. 1

High-Risk Patients

• Patients with previous ulcer bleeding have a 33% risk of rebleeding within 1-2 years and 40-50% risk over 10 years. 1, 5
• These patients require indefinite PPI therapy if they continue antiplatelet agents or anticoagulants. 1

Common Pitfalls to Avoid

• Do not assume PPI resistance without first confirming H. pylori eradication and NSAID discontinuation. 1
• Do not continue standard once-daily PPI dosing in patients with documented treatment failure; escalate to twice-daily dosing. 1
• Do not overlook delayed gastric emptying as a cause of inadequate PPI absorption. 3
• Do not use P-CABs as first-line therapy due to cost and limited safety data, but consider them in true PPI failures after excluding secondary causes. 1