Introduction

Continuous maintenance treatment (administration of a proton pump inhibitor [PPI] daily) and on-demand maintenance treatment (repeated administration of a PPI for several days whenever mild gastroesophageal reflux disease [GERD] symptoms recur) are commonly used in clinical practice. It remains unclear which maintenance treatment modality is most appropriate for GERD.

Aim

To compare on-demand treatment with continuous treatment using a PPI in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis (EE).

Patient Profile

• 304 patients with GERD symptoms and non-erosive GERD or mild EE (Los Angeles grade A or B)

Method

Study Design

• Prospective randomized multicenter trial (25 hospitals)
• Patients whose GERD symptoms improved after 4 weeks of pantoprazole 40 mg once daily before meals were randomly assigned to pantoprazole 20 mg either an on-demand (for GERD symptoms; stopped when symptoms improved for at least 2 days; and administered again if symptoms recurred) or a continuous maintenance treatment, and followed for 8, 16, and 24 weeks

Endpoints

• Primary outcome: proportion of unwillingness to continue the assigned maintenance treatment modality during the maintenance treatment period
• Secondary outcomes: change in the total scores of the self-evaluation questionnaire for GERD symptoms (SEQ-GERD) and GERD–health-related quality of life (GERD-HRQL), and the 5-scale Likert score about overall satisfaction
• Adverse events associated with PPIs and laboratory findings

Results

Efficacy

• The proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the noninferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%)
• On-demand treatment did not show non-inferiority versus continuous treatment in patients with non-erosive GERD and in those with mild EE
• Poorly controlled symptoms (35.8% vs 17.0%, P=0.009), no more symptoms (32.8% vs 37.7%), concern about adverse events (1.5% vs 7.6%), and dislike for intake of medicine (3.0% vs 7.6%) were the main reasons in the on-demand treatment group

• SEQ-GERD and GERD-HRQL scores improved significantly in the continuous treatment group versus on-demand group, particularly at week 8 and 16 of maintenance treatment
• The 5-scale Likert score (overall satisfaction) was significantly higher in the continuous group at week 8 and 16 of maintenance treatment versus the on-demand group, but not at week 24 of maintenance treatment
• Work impairment scores improved after maintenance therapy in both the groups, with no significant difference in the 2 groups.
• During maintenance treatment, PPIs usage was significantly lesser number of times by patients in the on-demand group (3.2 days a week) than in the continuous group (6.7 days a week); similar results were seen for the prescription cost

Figure 1: Comparison of the primary outcome in on-demand and continuous PPI treatment groups

Safety 

• The incidence of drug-related treatment-emergent adverse events did not differ between the on-demand (0.7%) and continuous (2.0%) treatment groups
• Serum gastrin levels were significantly elevated in the continuous treatment group, compared with the baseline levels (51.8 pg/mL vs 79.3 pg/mL, P<0.001), but did not alter in the on-demand treatment group (65.5 pg/mL vs 69.6 pg/mL, P=0.855)

Conclusion

• Continuous treatment was more suitable for the initial maintenance of non-erosive GERD or mild EE versus on-demand treatment
• The study suggested that stepping down to on-demand treatment could be considered after a sufficient period of continuous maintenance treatment

J Neurogastroenterol Motil 2023; 29: 460-469