Esomeprazole-prokinetic combination: A novel approach to managing GERD
Gastroesophageal reflux disease (GERD) is emerging as a major health concern, having a strikingly high prevalence rate of 7.6% to 33%, varying among the global population. (1) 30% of the GERD patients continue to manifest symptoms even after being treated with the standard doses of Proton Pump Inhibitors (PPI)s, a fact, well documented in researches. (2)
One- Third of Patients Fail to Respond with PPI
Besides the chief symptoms of heartburn and regurgitation, studies have demonstrated that 50% of GERD patients may have symptoms of esophageal dysmotility like epigastric discomfort or fullness, nausea, and early satiety. (3) With a multifactorial etiology, a widely variable healing rate of 60-70%, 20-30%, and 6-10% in the symptoms of GERD has been noted across different populations, in response to PPI monotherapy. (4) Specifically speaking, one-third of patients with GERD fail to respond symptomatically to a standard dose PPI, either partially or completely (4). Such unpredictable results warrant the addition of prokinetic agents, along with PPIs, thus assuring an optimized management therapy of GERD.
How does a prokinetic drug help in GERD?
One of the major key factors responsible for GERD is a motor imbalance of the lower esophageal sphincter (LES), leading to slow esophageal wall contractions, abnormal esophageal clearing, delayed gastric emptying, and increased transient LES relaxation. (5, 6). Prokinetic drugs work by raising the LES basal pressure, improving esophageal peristalsis, accelerating esophageal acid clearance, and facilitating gastric emptying.
Prokinetics also improve the pharmacokinetics of PPIs, which are usually unstable in gastric acid. Rapid and consistent peristalsis facilitates in rapid transit of PPIs into the intestine, exerting a better therapeutic effect. (7)
Among the prokinetics agents available, Metoclopramide, Domperidone, Mosapride, Itopride, and Cisapride have been widely studied as an add-on to PPI therapy for GERD.(8)
4 weeks of Treatment With PPI+ Prokinetic helps
A recent comprehensive meta-analysis (9) has identified mosapride, domperidone, acotiamide, and revexepride as effective prokinetics in GERD patients when combined with PPI. The authors further elaborated that patients treated for at least 4 weeks, those receiving PPI plus prokinetics therapy were found to show a greater reduction in GERD symptoms than patients receiving PPI monotherapy, thereby suggesting that while prescribing a combination of prokinetics and PPI to patients with GERD, a treatment regimen of at least 4 weeks should be recommended.
Esomeprazole –prokinetic combination: Fighting GERD at its best
Esomeprazole, regarded as the most potent acid suppressor among all the PPIs have already proven their supreme efficacy in managing GERD. (10)
Evidence-based studies supporting esomeprazole –prokinetic combination in GERD have been summarised below.
A study by Yu Kyung Cho and team, aimed at assessing the effect of Mosapride, a prokinetic drug, with esomeprazole on the esophageal peristaltic function in patients with GERD affirmed that the combination affected esophageal peristalsis by improving esophageal contractibility and lowering IBP, that could lead to facilitating esophageal bolus transit. (11)
Another study by Biltagi and co-workers, that examined the efficacy of esomeprazole monotherapy vs its combination with domperidone, a prokinetic, in those who had GERD, concluded that a combination of domperidone and esomeprazole was more effective in improving the endoscopic reflux score. (12)
Yet another trial investigating the efficacy and safety of esomeprazole single therapy versus mosapride and esomeprazole combined therapy in patients with GERD highlighted that tendency for upper abdominal pain, belching, and total GERD symptoms scores improve more rapidly in the combination group, suggesting that esomeprazole and mosapride are useful for rapid improvement of specific GERD symptoms. (13)
A major Indian study evaluating the clinical efficacy, tolerability, and safety of a fixed-dose combination of Esomeprazole 20 mg and sustained release (SR) Domperidone 30mg administered once daily in adult Indian patients for the symptomatic relief of dyspepsia associated with GERD has concluded that the combination drug therapy was very effective and a well-tolerated therapeutic option in the management of symptomatic relief of GERD.(14)
With such a rising number of researches targeted at exploring the unique dual therapy of esomeprazole plus prokinetics, establishing its unparalleled authority in managing GERD remains only a matter of time.
What Guidelines Recommend
Acknowledging the superior efficacy of dual drug therapy in GERD, an Asia-Pacific consensus on the management of gastroesophageal reflux disease has concluded that the use of prokinetic agents as adjunctive therapy to PPIs may have a role in the treatment of GERD in Asia. (15) Current guidelines recommend the use of prokinetics in combination with PPIs in GERD patients who exhibit an insufficient response to PPI alone. (4)
Take home message for clinicians
- Evidence points out certain key facts about the combination of esomeprazole with a prokinetic, which if implemented properly can lead to adequate control of GERD-related symptoms.
ï‚· Esomeprazole-prokinetic acts best in cases of refractory GERD, or when symptoms keep relapsing despite completion of PPI monotherapy.
ï‚· Owing to the synergistic action of the two drugs together, studies have affirmed their superior success in managing GERD, specifically when advised for more than 4 weeks continuously.
ï‚· Physicians should keep themselves updated to utilize the advantages provided by the combination therapy, as and when needed.
Conclusion
With growing evidence highlighting that there has been a drastic increase in GERD prevalence since 1995, particularly in East Asia (9), it is high time to consider prokinetics as an adjunct to PPIs for successful resolution of GERD. Future studies based on empirical drug therapy of esomeprazole and prokinetic drugs targeted to treat GERD, depending on individualized needs and severity of the disease will lead the way forward in establishing the best pharmacological remedy for GERD.
References
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