Takeuchi Toshihisa, Oota Kazuhiro, Harada Satoshi, Edogawa Shoko, Kojima Yuichi, Sanomura Makoto, Sakaguchi Masahiro, Hayashi Katsuyoshi, Hongoh Yasushi, Itabashi Tsukasa, Kitae Hidehiro, Hoshimoto Masahiro, Takeuchi Nozomi, Higuchi Kazuhide
The Second Department of Internal Medicine, Osaka Medical College, Japan.
Intern Med. 2015;54(2):97-105. doi: 10.2169/internalmedicine.54.3412. Epub 2015 Jan 15.
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.
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.
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.
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.
我们研究了与质子泵抑制剂（PPI）难治性胃食管反流病（GERD）症状相关的因素，特别是关于胃酸、CYP2C19基因分型和心理方面的因素。
初始治疗后GERD症状频率量表（FSSG）评分≥8分的患者换用雷贝拉唑治疗，剂量为每日20mg，共8周。我们研究了PPI难治性GERD症状的改善率、背景因素、医院焦虑抑郁量表（HADS）评分以及CYP2C19基因分型。纳入60例在过去6个月内经内镜诊断为反流性食管炎且接受过每日20mg奥美拉唑治疗8周或更长时间的患者。
71.6%的患者在接受每日20mg奥美拉唑治疗≥8周后，FSSG评分降至<8分，GERD症状得到改善。与奥美拉唑难治性GERD症状相关的显著因素包括病程较长（p = 0.0004）和HADS评分较高（p = 0.01）。在奥美拉唑难治性病例中，换用雷贝拉唑后仅有23.5%的患者症状改善。换药前后FSSG平均评分（p = 0.089）或HADS评分（p = 0.182）无显著差异。雷贝拉唑治疗反应不佳的患者中，92%为CYP2C19基因分型的同/杂合广泛代谢者。
我们的研究结果表明，考虑到可能的心理测量因素以及对于PPI难治性GERD症状需要比双倍剂量PPI更强的抑酸作用的患者，将PPI从奥美拉唑（每日20mg）换为雷贝拉唑（每日20mg）并非改善PPI难治性GERD症状的有效治疗策略。
