Characteristics of refractory gastroesophageal reflux disease (GERD) symptoms -is switching proton pump inhibitors based on the patient's CYP2C19 genotype an effective management strategy?
OBJECTIVE
We investigated factors related to proton pump inhibitor (PPI) -refractory gastroesophageal reflux disease (GERD) symptoms, particularly with respect to acid, the CYP2C19 genotype and psychological aspects.


METHODS
Patients with an Frequency Scale for the Symptoms of GERD (FSSG) score of ≥8 after the initial treatment were switched to therapy with rabeprazole at a dose of 20 mg once daily for eight weeks. We investigated the rate of improvement in PPI-refractory GERD symptoms, background factors, the Hospital Anxiety and Depression Scale (HADS) score and the CYP2C19 genotype. Patients Sixty patients endoscopically diagnosed with reflux esophagitis within the past six months who had received omeprazole at a dose of 20 mg once daily for eight weeks or longer were enrolled.


RESULTS
In 71.6% of the patients, the FSSG score decreased to <8 after treatment with omeprazole at a dose of 20 mg once daily for ≥8 weeks, resulting in improvements in their GERD symptoms. Significant factors related to omeprazole-refractory GERD symptoms included a longer disease duration (p=0.0004) and higher HADS score (p=0.01). Among the omeprazole-refractory cases, only 23.5% of the patients showed symptom improvement after switching to rabeprazole. There were no significant differences in the average scores for FSSG (p=0.089) or HADS (p=0.182), before or after the drug change. A total of 92% of the rabeprazole poor responders were homo/hetero extensive metabolizers for the CYP2C19 genotype.


CONCLUSIONS
Our findings suggest that switching the PPI from omeprazole (20 mg once daily) to rabeprazole (20 mg once daily) is not a significant effective therapeutic strategy for improving PPI-refractory GERD symptoms, taking into consideration possible psychometric factors and patients who require stronger acid suppression than that achieved with a double dose of PPIs for PPI-refractory GERD symptoms.
The Second Department of Internal Medicine, Osaka Medical College, Japan.
Toshihisa
T
Takeuchi
Kazuhiro
K
Oota
Satoshi
S
Harada
Shoko
S
Edogawa
Yuichi
Y
Kojima
Makoto
M
Sanomura
Masahiro
M
Sakaguchi
Katsuyoshi
K
Hayashi
Yasushi
Y
Hongoh
Tsukasa
T
Itabashi
Hidehiro
H
Kitae
Masahiro
M
Hoshimoto
Nozomi
N
Takeuchi
Kazuhide
K
Higuchi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000453:epidemiology; D001007:Anxiety / Q000453:epidemiology; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D003863:Depression / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D016099:Endoscopy, Gastrointestinal; D004942:Esophagitis, Peptic / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D064750:Rabeprazole / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012907:Smoking / Q000453:epidemiology; D055815:Young Adult
D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole