The Cost Effectiveness of Adjunctive Treatments for Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease

Abstract

Background and objective: Half of patients with gastroesophageal reflux disease (GERD) experience persistent symptoms while on proton pump inhibitors (PPIs), thus driving efforts to develop novel adjunctive therapies for PPI-refractory GERD. An economic analysis was performed to establish at what cost and efficacy such potential medications are likely to become cost effective in clinical practice.

Methods: A Markov decision model was used to examine a hypothetical cohort of patients being evaluated for PPI-refractory GERD in the USA. The model compared 3 strategies: (1) usual care (i.e., upfront diagnostic testing with upper endoscopy ± ambulatory pH testing); (2) use of a PPI-adjunctive therapy after positive ambulatory pH testing; and (3) empiric use of a PPI-adjunctive therapy (i.e., diagnostic testing only after failing empiric treatment). The primary outcome was incremental cost per quality-adjusted life year (QALY) gained (third-party payer perspective) over a 10-year time horizon using a willingness to pay threshold of $100,000/QALY.

Results: In two-way sensitivity analyses varying the cost and effectiveness of the PPI-adjunctive therapy, most combinations revealed that use of the medication after positive pH testing was the most cost-effective approach. Empiric treatment was the preferred strategy only when the therapy was highly efficacious (≥ 87.5% response rate) and low cost (≤ $109/month). Use of PPI-adjunctive treatments were not cost effective when the cost exceeded $1150/month.

Conclusion: Use of PPI-adjunctive therapies in those with persistent GERD symptoms may become cost effective when guided by ambulatory pH tests. These data can guide investigators, industry, and payers as they develop, validate, and price new treatments for PPI-refractory GERD.

Fig. 1

Truncated decision model. (White square) decision node, (Circled capital letter M) Markov node, (white circle) probability node, (left pointing white triangle) terminal node. BID twice daily, EE erosive esophagitis, EGD esophagogastroduodenoscopy, GI gastroenterologist, GERD gastroesophageal reflux disease, PPI proton pump inhibitor

Fig. 2

Nomogram depicting the preferred strategy across various PPI-adjunctive therapy costs and effectiveness in the base-case scenario (37.3% of PPI-refractory GERD patients have positive pH testing on PPI) using a WTP of $100,000/QALY. Across most cost and effectiveness combinations, use of the PPI-adjunctive therapy after positive pH testing was the most cost-effective approach. GERD gastroesophageal reflux disease, PPI proton pump inhibitor, QALY quality-adjusted life year, WTP willingness to pay

Fig. 3

Nomograms depicting the preferred strategy across various therapy costs and effectiveness, stratified by the percent of PPI-refractory GERD patients with positive pH testing on PPI. GERD gastroesophageal reflux disease, PPI proton pump inhibitor

Fig. 4

At varying PPI-adjunctive therapy costs and effectiveness, probabilistic sensitivity analyses were performed using 10,000 trials. At each cost and effectiveness combination, the percentage of trials for each arm where it was the most cost-effective using a WTP of $100,000/QALY was identified. Combinations highlighted in red show when the PPI-adjunctive therapy after diagnostic testing arm was the preferred strategy in ≥ 75% of trials; for combinations where no strategy reached the 75% threshold, it was deemed as equivocal. PPI proton pump inhibitor, QALY quality-adjusted life year, WTP willingness to pay