Clinical characteristics of elderly patients with proton pump inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who responded to rikkunshito

Abstract

Background: The incidence and severity of gastroesophageal reflux disease (GERD) in Japan tends to increase in elderly women. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and improves gastric emptying and gastric accommodation. Our previous prospective randomized placebo-controlled study showed that RKT combined with a standard-dose of rabeprazole (RPZ) significantly improved the acid-related dysmotility symptoms (ARD) in elderly patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study aimed to evaluate clinical characteristics of elderly PPI-refractory NERD patients with ARD symptoms who responded to RKT.

Methods: Two hundred forty-two patients with PPI-refractory NERD were randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) + RKT (7.5 g/t.i.d.) (RKT group) or RPZ + placebo (PL group). Among them, 95 were elderly (≥65 years) with ARD (RKT group: n = 52; PL group: n = 43). We analyzed the changes using the 12 subscale score of frequency scale for the symptoms of GERD (FSSG) and 15 items of the Gastrointestinal Symptom Rating Scale at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups.

Results: There were no marked differences in baseline demographic or clinical characteristics in the 2 groups except for rate of current smoking. The FSSG score (mean ± SD at 0, 4, and 8 weeks) in both the RKT (16.0 ± 7.0; 9.9 ± 8.4; 7.0 ± 6.4) and PL (15.1 ± 6.4; 10.9 ± 6.7, 11.1 ± 8.5) groups significantly decreased after treatment. However, the degree of improvement of total and ARD scores of FSSG after the 8-week treatment was significantly greater in the RKT group than in the PL group. Combination therapy with RKT for 8 weeks showed significant improvement in 3 subscale scores (abdominal bloating, heavy feeling in stomach and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain.

Conclusions: RKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. Thus, RKT was particularly effective for resolving postprandial GERD symptoms (heavy feeling in stomach, sick feeling, and heartburn after meals).

Trial registration: (UMIN000005880).

Figure 1

Patients enrolled in this study. Of 242 patients with a clinical diagnosis of PPI-refractory NERD, 95 were elderly patients (≥65 years) with ARD. ARD, acid-related dysmotility symptom; RKT group: rikkunshito (7.5 g/day 3 times) + rabeprazole (10 mg/day), PL group: placebo (7.5 g/day 3 times) + rabeprazole (10 mg/day).

Figure 2

Changes in FSSG scores after treatments of RKT or placebo. (A) Changes in total, ARD and RS scores of FSSG after the 4- and 8-week treatment. (B) Improvement degrees of total, ARD and RS scores of FSSG after the 4- and 8-week treatment. Values are expressed as mean ± SD. **P < 0.01 vs. before treatment (Wilcoxon’s signed rank test). ^#P < 0.05, ^##P < 0.01 significant difference between each paired group (Wilcoxon’s signed rank test).

Figure 3

Improvement degrees of 12 subscale scores of FSSG after the 8-week treatment in the RKT and placebo 2 groups. (A) Improvement degrees in 5 subscale scores of ARD after the 8-week treatment. (B) Improvement degrees in 7 subscale scores of RS after the 8-week treatment. Values were expressed as mean ± SD. ^#P < 0.05, ^##P < 0.01 significant difference between each paired group (Wilcoxon’s signed rank test).