Is there any acid peptic disease that is refractory to proton pump inhibitors?

Non-healing and delayed healing during acid inhibition treatment depend on the extent to which acid and 'non-acid' factors are causative in the particular acid peptic disease, and on the effectiveness and duration of acid suppression. Refractoriness (defined arbitrarily) occurs less often with proton pump inhibitors than with H2-receptor antagonists as the former decrease acid more effectively; H2-receptor antagonist-refractory disease usually responds to treatment with proton pump inhibitors. In Rotherham, 5-10% of duodenal ulcer and gastric ulcer patients are refractory (not healed after > or = 3 months of standard-dose H2-receptor antagonist). In patients with oesophagitis 15% are refractory to high-dose H2-receptor antagonist (for example, 3.2 g cimetidine daily) and 5% to standard-dose proton pump inhibitors (for example, 20 mg omeprazole daily). In controlled clinical trials of patients with refractory duodenal ulcer, healing at 8 weeks with 40 mg omeprazole o.m. vs. continued standard-dose H2-receptor antagonist was 98% vs. 60%; and with 40 mg omeprazole vs. continued high-dose H2-receptor antagonist (2 g + 3 g cimetidine, that is, ultra-refractory disease) was 92% vs. 67%. After healing, in open studies, relapse with maintenance 400-800 mg cimetidine nocte was 45-69% at one year, but 0% with 40 mg omeprazole administered for up to 6.5 years. For 53 patients with refractory gastric ulcer, in an open study, healing with omeprazole 40 mg o.m. occurred in 94% at 8 weeks, and none relapsed on long-term maintenance treatment at this dose. In controlled trials of patients with refractory oesophagitis, healing at 12 weeks with 40 mg omeprazole o.m. vs. high-dose ranitidine (300 mg b.d.) was 90% vs. 47%, and with maintenance 20 mg omeprazole o.m. vs. 150 mg ranitidine b.d., relapse at 1 year was 32% vs. 88%. In conclusion, acid peptic disease refractory to H2-receptor antagonists is uncommon and treatment with proton pump inhibitors is effective. Refractoriness to proton pump inhibitors is rare.