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难治性胃食管反流病的药物治疗研究进展
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Abstract:
胃食管反流病(GERD)是一种由胃、十二指肠内容物反流引起的常见的消化系统疾病，常见症状有反酸、烧心、胸痛、嗳气和吞咽困难。GERD发病率在世界范围内很高(2.5%~51.2%)。在大多数情况下，质子泵抑制剂(PPI)可有效治愈病变和改善症状，但高达30%的GERD患者对PPI治疗反应不足。中国专家共识将经双倍标准剂量抑酸剂治疗8周后，反流、烧心等症状仍无明显改善的GERD定义为难治性胃食管反流病(RGERD)。RGERD严重影响患者生活质量，也会增加医疗保健资源的消耗。本文就近年来RGERD药物治疗的研究进展作一综述。
Gastroesophageal reflux disease (GERD) is a common digestive system disease caused by reflux of stomach and duodenal contents, with common symptoms including acid reflux, heartburn, chest pain, belching and dysphagia. The incidence of GERD is high worldwide (2.5%~51.2%). In most cases, proton pump inhibitors (PPIs) are effective in curing lesions and improving symptoms, but up to 30% of GERD patients do not respond adequately to PPI treatment. Chinese experts agree that GERD with no significant improvement in reflux, heartburn and other symptoms after 8 weeks of treatment with double standard dose of acid suppressants is defined as refractory gastroesophageal reflux disease (RGERD). RGERD seriously affects the quality of life of patients and also increases the consumption of healthcare resources. This article reviews the recent progress in drug therapy of RGERD.
| [1] | Yadlapati, R., Gyawali, C.P. and Pandolfino, J.E. (2022) AGA Clinical Practice Update on the Personalized Approach to the Evaluation and Management of GERD: Expert Review. Clinical Gastroenterology and Hepatology, 20, 984-994. https://doi.org/10.1016/j.cgh.2022.01.025 |
| [2] | Gyawali, C.P. and Fass, R. (2018) Management of Gastroesophageal Reflux Disease. Gastroenterology, 154, 302-318. https://doi.org/10.1053/j.gastro.2017.07.049 |
| [3] | Gunaratnam, N.T., Jessup, T.P., Inadomi, J., et al. (2006) Sub-Optimal Proton Pump Inhibitor Dosing Is Prevalent in Patients with Poorly Controlled Gastro-Oesophageal Reflux Disease. Alimentary Pharmacology & Therapeutics, 23, 1473-1477. https://doi.org/10.1111/j.1365-2036.2006.02911.x |
| [4] | Zerbib, F., Bredenoord, A.J., Fass, R., et al. (2021) ESNM/ANMS Consensus Paper: Diagnosis and Management of Refractory Gastro-Esophageal Reflux Disease. Neurogastroenterology & Motility, 33, e14075. https://doi.org/10.1111/nmo.14075 |
| [5] | 张海洋, 张丽. 基于24 h多通道食管腔内阻抗-pH监测的难治性胃食管反流病诊治进展[J]. 国际消化病杂志, 2024, 44(1): 1-4. |
| [6] | Gyawali, C.P., Kahrilas, P.J., Savarino, E., et al. (2018) Modern Diagnosis of GERD: The Lyon Consensus. Gut, 67, 1351-1362. https://doi.org/10.1136/gutjnl-2017-314722 |
| [7] | Vakil, N., van Zanten, S.V., Kahrilas, P., et al. (2006) The Montreal Definition and Classification of Gastroesophageal Reflux Disease: A Global Evidence-Based Consensus. American Journal of Gastroenterology, 101, 1900-1920. https://doi.org/10.1111/j.1572-0241.2006.00630.x |
| [8] | 张阿静, 姚文柱, 狄佳, 等. 非糜烂性反流病、反流高敏感和功能性烧心患者食管pH-阻抗反流模式比较[J]. 南方医科大学学报, 2020, 40(10): 1507-1512. |
| [9] | 廖思宇, 刘咪咪, 周婧, 等. 基于里昂共识诊断的内镜阴性烧心患者的食管动力及反流特征比较[J]. 西安交通大学学报(医学版), 2022, 43(4): 545-549. |
| [10] | Johnston, B.T., Lewis, S.A., Collins, J.S., et al. (1995) Acid Perception in Gastro-Oesophageal Reflux Disease Is Dependent on Psychosocial Factors. Scandinavian Journal of Gastroenterology, 30, 1-5. https://doi.org/10.3109/00365529509093228 |
| [11] | Piesman, M., Hwang, I., Maydonovitch, C., et al. (2007) Nocturnal Reflux Episodes Following the Administration of a Standardized Meal. Does Timing Matter? American Journal of Gastroenterology, 102, 2128-2134. https://doi.org/10.1111/j.1572-0241.2007.01348.x |
| [12] | Singh, M., Lee, J., Gupta, N., et al. (2013) Weight Loss Can Lead to Resolution of Gastroesophageal Reflux Disease Symptoms: A Prospective Intervention Trial. Obesity, 21, 284-290. https://doi.org/10.1002/oby.20279 |
| [13] | Eusebi, L.H., Ratnakumaran, R., Yuan, Y., et al. (2018) Global Prevalence of, and Risk Factors for, Gastro-Oesophageal Reflux Symptoms: A Meta-Analysis. Gut, 67, 430-440. https://doi.org/10.1136/gutjnl-2016-313589 |
| [14] | Nilsson, M., Johnsen, R., Ye, W., et al. (2004) Lifestyle Related Risk Factors in the Aetiology of Gastro-Oesophageal Reflux. Gut, 53, 1730-1735. https://doi.org/10.1136/gut.2004.043265 |
| [15] | Kaltenbach, T., Crockett, S. and Gerson, L.B. (2006) Are Lifestyle Measures Effective in Patients with Gastroesophageal Reflux Disease? An Evidence-Based Approach. Archives of Internal Medicine, 166, 965-971. https://doi.org/10.1001/archinte.166.9.965 |
| [16] | Wolfe, M.M. and Sachs, G. (2000) Acid Suppression: Optimizing Therapy for Gastroduodenal Ulcer Healing, Gastroesophageal Reflux Disease, and Stress-Related Erosive Syndrome. Gastroenterology, 118, S9-S31. https://doi.org/10.1016/S0016-5085(00)70004-7 |
| [17] | Van Soest, E.M., Siersema, P.D., Dieleman, J.P., et al. (2006) Persistence and Adherence to Proton Pump Inhibitors in Daily Clinical Practice. Alimentary Pharmacology & Therapeutics, 24, 377-385. https://doi.org/10.1111/j.1365-2036.2006.02982.x |
| [18] | Gosselin, A., Luo, R., Lohoues, H., et al. (2009) The Impact of Proton Pump Inhibitor Compliance on Health-Care Resource Utilization and Costs in Patients with Gastroesophageal Reflux Disease. Value Health, 12, 34-39. https://doi.org/10.1111/j.1524-4733.2008.00399.x |
| [19] | Hungin, A.P., Rubin, G. and O’Flanagan, H. (1999) Factors Influencing Compliance in Long-Term Proton Pump Inhibitor Therapy in General Practice. British Journal of General Practice, 49, 463-464. |
| [20] | Scarpignato, C. and Hunt, R.H. (2021) Editorial: Acid Suppression with Potassium-Competitive Acid Blockers Dismissing Genotype Concerns. Alimentary Pharmacology & Therapeutics, 53, 187-188. https://doi.org/10.1111/apt.16139 |
| [21] | Fass, R., Murthy, U., Hayden, C.W., et al. (2000) Omeprazole 40 mg Once a Day Is Equally Effective as Lansoprazole 30 mg Twice a Day in Symptom Control of Patients with Gastro-Oesophageal Reflux Disease (GERD) Who Are Resistant to Conventional-Dose Lansoprazole Therapy—A Prospective, Randomized, Multi-Centre Study. Alimentary Pharmacology & Therapeutics, 14, 1595-1603. https://doi.org/10.1046/j.1365-2036.2000.00882.x |
| [22] | Klok, R.M., Postma, M.J., van Hout, B.A., et al. (2003) Meta-Analysis: Comparing the Efficacy of Proton Pump Inhibitors in Short-Term Use. Alimentary Pharmacology & Therapeutics, 17, 1237-1245. https://doi.org/10.1046/j.1365-2036.2003.01562.x |
| [23] | Graham, D.Y. and Tansel, A. (2018) Interchangeable Use of Proton Pump Inhibitors Based on Relative Potency. Clinical Gastroenterology and Hepatology, 16, 800-808. https://doi.org/10.1016/j.cgh.2017.09.033 |
| [24] | Armstrong, D., Marshall, J.K., Chiba, N., et al. (2005) Canadian Consensus Conference on the Management of Gastroesophageal Reflux Disease in Adults—Update 2004. Canadian Journal of Gastroenterology, 19, 15-35. https://doi.org/10.1155/2005/836030 |
| [25] | Yadlapati, R., Vaezi, M.F., Vela, M.F., et al. (2018) Management Options for Patients with GERD and Persistent Symptoms on Proton Pump Inhibitors: Recommendations from an Expert Panel. American Journal of Gastroenterology, 113, 980-986. https://doi.org/10.1038/s41395-018-0045-4 |
| [26] | Dal-Paz, K., Moraes-Filho, J.P., Navarro-Rodriguez, T., et al. (2012) Low Levels of Adherence with Proton Pump Inhibitor Therapy Contribute to Therapeutic Failure in Gastroesophageal Reflux Disease. Diseases of the Esophagus, 25, 107-113. https://doi.org/10.1111/j.1442-2050.2011.01227.x |
| [27] | Hillman, L., Yadlapati, R., Thuluvath, A.J., et al. (2017) A Review of Medical Therapy for Proton Pump Inhibitor Nonresponsive Gastroesophageal Reflux Disease. Diseases of the Esophagus, 30, 1-15. https://doi.org/10.1093/dote/dox055 |
| [28] | Mainie, I., Tutuian, R. and Castell, D.O. (2008) Addition of a H2 Receptor Antagonist to PPI Improves Acid Control and Decreases Nocturnal Acid Breakthrough. Journal of Clinical Gastroenterology, 42, 676-679. https://doi.org/10.1097/MCG.0b013e31814a4e5c |
| [29] | Rackoff, A., Agrawal, A., Hila, A., et al. (2005) Histamine-2 Receptor Antagonists at Night Improve Gastroesophageal Reflux Disease Symptoms for Patients on Proton Pump Inhibitor Therapy. Diseases of the Esophagus, 18, 370-373. https://doi.org/10.1111/j.1442-2050.2005.00518.x |
| [30] | Lei, W.Y., Hung, J.S., Liu, T.T., et al. (2017) Influence of GABA-B Agonist Baclofen on Capsaicin-Induced Excitation of Secondary Peristalsis in Humans. Clinical and Translational Gastroenterology, 8, e120. https://doi.org/10.1038/ctg.2017.46 |
| [31] | Hoshino, S., Kawami, N., Takenouchi, N., et al. (2017) Efficacy of Vonoprazan for Proton Pump Inhibitor-Resistant Reflux Esophagitis. Digestion, 95, 156-161. https://doi.org/10.1159/000456072 |
| [32] | Zou, S., Ouyang, M., Cheng, Q., et al. (2024) Acid-Suppressive Drugs: A Systematic Review and Network Meta-Analysis of Their Nocturnal Acid-Inhibitory Effect. Pharmacotherapy, 44, 171-183. https://doi.org/10.1002/phar.2899 |
| [33] | Koek, G.H., Sifrim, D., Lerut, T., et al. (2003) Effect of the GABAB Agonist Baclofen in Patients with Symptoms and Duodeno-Gastro-Oesophageal Reflux Refractory to Proton Pump Inhibitors. Gut, 52, 1397-1402. https://doi.org/10.1136/gut.52.10.1397 |
| [34] | Li, S., Shi, S., Chen, F., et al. (2014) The Effects of Baclofen for the Treatment of Gastroesophageal Reflux Disease: A Meta-Analysis of Randomized Controlled Trials. Gastroenterology Research and Practice, 2014, Article ID: 307805. https://doi.org/10.1155/2014/307805 |
| [35] | Shaheen, N.J., Denison, H., Bj？rck, K., et al. (2013) Efficacy and Safety of Lesogaberan in Gastro-Oesophageal Reflux Disease: A Randomised Controlled Trial. Gut, 62, 1248-1255. https://doi.org/10.1136/gutjnl-2012-302737 |
| [36] | Lee, H., Kim, J.H., Min, B.H., et al. (2010) Efficacy of Venlafaxine for Symptomatic Relief in Young Adult Patients with Functional Chest Pain: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. American Journal of Gastroenterology, 105, 1504-1512. https://doi.org/10.1038/ajg.2010.82 |
| [37] | Sawada, A., Hashimoto, A., Uemura, R., et al. (2020) Effect of EP1 Receptor Antagonist on Transient Lower Esophageal Sphincter Relaxations in Humans. Digestion, 101, 270-278. https://doi.org/10.1159/000499333 |
| [38] | Rouzade-Dominguez, M.L., Pezous, N., David, O.J., et al. (2017) The Selective Metabotropic Glutamate Receptor 5 Antagonist Mavoglurant (AFQ056) Reduces the Incidence of Reflux Episodes in Dogs and Patients with Moderate to Severe Gastroesophageal Reflux Disease. Neurogastroenterology & Motility, 29, e13058. https://doi.org/10.1111/nmo.13058 |
| [39] | Fackler, W.K., Ours, T.M., Vaezi, M.F., et al. (2002) Long-Term Effect of H2RA Therapy on Nocturnal Gastric Acid Breakthrough. Gastroenterology, 122, 625-632. https://doi.org/10.1053/gast.2002.31876 |
| [40] | Usai-Satta, P., Bellini, M., Morelli, O., et al. (2020) Gastroparesis: New Insights into an Old Disease. World Journal of Gastroenterology, 26, 2333-2348. https://doi.org/10.3748/wjg.v26.i19.2333 |
| [41] | Mermelstein, J., Chait, M.A. and Chait, M.M. (2018) Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease: Challenges and Solutions. Clinical and Experimental Gastroenterology, 11, 119-134. https://doi.org/10.2147/CEG.S121056 |
| [42] | Ren, L.H., Chen, W.X., Qian, L.J., et al. (2014) Addition of Prokinetics to PPI Therapy in Gastroesophageal Reflux Disease: A Meta-Analysis. World Journal of Gastroenterology, 20, 2412-2419. https://doi.org/10.3748/wjg.v20.i9.2412 |
| [43] | Bron, B. and Massih, L. (1980) Domperidone: A Drug with Powerful Action on the Lower Esophageal Sphincter Pressure. Digestion, 20, 375-378. https://doi.org/10.1159/000198476 |
| [44] | Taghvaei, T., Kazemi, A., Hosseini, V., et al. (2019) Evaluation of the Additive Effect of Domperidone on Patients with Refractory Gastroesophageal Reflux Disease; A Randomized Double Blind Clinical Trial. Middle East Journal of Digestive Diseases, 11, 24-31. https://doi.org/10.15171/mejdd.2018.124 |
| [45] | Kessing, B.F., Smout, A.J., Bennink, R.J., et al. (2014) Prucalopride Decreases Esophageal Acid Exposure and Accelerates Gastric Emptying in Healthy Subjects. Neurogastroenterology & Motility, 26, 1079-1086. https://doi.org/10.1111/nmo.12359 |
| [46] | Hershcovici, T. and Fass, R. (2011) Pharmacological Management of GERD: Where Does It Stand Now? Trends in Pharmacological Sciences, 32, 258-264. https://doi.org/10.1016/j.tips.2011.02.007 |
| [47] | Richter, J.E. (2007) How to Manage Refractory GERD. Nature Clinical Practice Gastroenterology & Hepatology, 4, 658-664. https://doi.org/10.1038/ncpgasthep0979 |
| [48] | Gweon, T.G., Park, J.H., Kim, B.W., et al. (2018) Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease. Gut and Liver, 12, 46-50. https://doi.org/10.5009/gnl17078 |
| [49] | Savarino, V., Pace, F. and Scarpignato, C. (2017) Randomised Clinical Trial: Mucosal Protection Combined with Acid Suppression in the Treatment of Non-Erosive Reflux Disease—Efficacy of Esoxx, a Hyaluronic Acid-Chondroitin Sulphate Based Bioadhesive Formulation. Alimentary Pharmacology & Therapeutics, 45, 631-642. https://doi.org/10.1111/apt.13914 |
| [50] | 林燕芳, 王雯, 王宝珊, 等. miR-144在大鼠反流性食管炎中的作用和机制[J]. 临床消化病杂志, 2019, 31(1): 1-5. |
| [51] | Kuipers, T., Oude, N.R., van den Wijngaard, R.M., et al. (2024) Ziverel for PPI-Refractory Reflux Symptoms: Efficacy and Mechanisms of Action in Humans. Scandinavian Journal of Gastroenterology, 59, 384-389. https://doi.org/10.1080/00365521.2023.2290457 |
| [52] | Müller, M., Labenz, G., Borkenstein, D.P., et al. (2019) Alginate on Demand as Add-on for Patients with Gastro-Oesophageal Reflux Disease and Insufficient PPI Effect. Deutsche Medizinische Wochenschrift, 144, e30-e35. https://doi.org/10.1055/a-0736-5959 |
| [53] | Reimer, C., L？drup, A.B., Smith, G., et al. (2016) Randomised Clinical Trial: Alginate (Gaviscon Advance) vs. Placebo as Add-on Therapy in Reflux Patients with Inadequate Response to a Once Daily Proton Pump Inhibitor. Alimentary Pharmacology & Therapeutics, 43, 899-909. https://doi.org/10.1111/apt.13567 |
| [54] | Savarino, E., Gemignani, L., Pohl, D., et al. (2011) Oesophageal Motility and Bolus Transit Abnormalities Increase in Parallel with the Severity of Gastro-Oesophageal Reflux Disease. Alimentary Pharmacology & Therapeutics, 34, 476-486. https://doi.org/10.1111/j.1365-2036.2011.04742.x |
| [55] | Varia, I., Logue, E., O’Connor, C., et al. (2000) Randomized Trial of Sertraline in Patients with Unexplained Chest Pain of Noncardiac Origin. American Heart Journal, 140, 367-372. https://doi.org/10.1067/mhj.2000.108514 |
| [56] | Rohof, W.O., Bennink, R.J., de Ruigh, A.A., et al. (2012) Effect of Azithromycin on Acid Reflux, Hiatus Hernia and Proximal Acid Pocket in the Postprandial Period. Gut, 61, 1670-1677. https://doi.org/10.1136/gutjnl-2011-300926 |
| [57] | Malekpour, H., Noori, A., Abdi, S., et al. (2023) Is the Addition of Sublingual Melatonin to Omeprazole Superior to Omeprazole Alone in the Management of Gastroesophageal Reflux Disease Symptoms: A Clinical Trial. Turkish Journal of Gastroenterology, 34, 1206-1211. https://doi.org/10.5152/tjg.2023.23021 |
| [58] | 孔凯, 杨正武. 氟哌噻吨美利曲辛辅助治疗难治性胃食管反流病疗效及安全性meta分析[J]. 现代医药卫生, 2020, 36(13): 1964-1969. |
| [59] | Krarup, A.L., Ny, L., Gunnarsson, J., et al. (2013) Randomized Clinical Trial: Inhibition of the TRPV1 System in Patients with Nonerosive Gastroesophageal Reflux Disease and a Partial Response to PPI Treatment Is Not Associated with Analgesia to Esophageal Experimental Pain. Scandinavian Journal of Gastroenterology, 48, 274-284. https://doi.org/10.3109/00365521.2012.758769 |
| [60] | Vaezi, M.F., Fass, R., Vakil, N., et al. (2020) IW-3718 Reduces Heartburn Severity in Patients with Refractory Gastroesophageal Reflux Disease in a Randomized Trial. Gastroenterology, 158, 2093-2103. https://doi.org/10.1053/j.gastro.2020.02.031 |
| [61] | 陆明军, 谭诗云. 舒肝解郁胶囊联合常规治疗对难治性胃食管反流病患者的症状改善、心理精神及生活质量的影响[J]. 广西医学, 2019, 41(18): 2301-2305, 2325. |
| [62] | 石俊生. 温针灸联合健脾和胃降逆汤治疗难治性胃食管反流病的效果分析[J]. 医学理论与实践, 2022, 35(18): 3112-3114. |
| [63] | 刘亚欣. 辛开苦降法结合穴位埋线干预难治性胃食管反流病患者生活质量研究[D]: [硕士学位论文]. 苏州: 中国中医科学院, 2019. |
