Night-time GERD: Understanding the Role of Esomeprazole

The association of chronic GERD with reflux esophagitis, sleep inadequacy, reduced work productivity due to increased daytime sleepiness, and poor health-related quality of life has long been established (5,6,7). To complicate matters, growing evidence highlights that 79% of patients reporting GERD suffer from nocturnal symptoms (8, 9,10). According to a review article by Orr et al, nighttime heartburn and sleep-related gastro-oesophageal reflux (GOR) represent a distinct clinical entity that deserves specific attention in the diagnosis and optimal treatment of GERD(11). Life-threatening medical complications such as oesophagitis, Barrett's oesophagus, laryngeal disorders such as laryngopharyngitis, and pulmonary aspiration can be aggravated in cases of moderate to severe chronic GERD(12).

Night-time GERD occurs as a result of prolonged acid contact with the gastroesophageal mucosa, being further aggravated by a decreased ability to neutralize reflux events owing to lower saliva production, reduced swallowing frequency, and gastric emptying at night (13).

Acid suppression by proton pump inhibitors (PPIs) forms the cornerstone of managing GERD. Over the years, the efficacy of various PPIs like lansoprazole, omeprazole, and pantoprazole has been extensively studied. Among these, of particular importance is Esomeprazole, which has been shown to have more potent acid suppression compared to other PPIs, due to an improved pharmacokinetic profile (14,15,16).

Esomeprazole: Molecular background

Esomeprazole is the latest PPI, made up of a single active optical isomer, specifically the S-isomer of omeprazole (17). Currently approved by FDA for use in the treatment of symptomatic GERD, including healing and maintenance of healing of erosive esophagitis (18), this drug has an edge over other PPIs with enhanced pharmacokinetic and pharmacodynamic features, owing to its molecular composition.

A trial by Andersson T et al demonstrated that Esomeprazole magnesium daily was more effective than omeprazole, with inhibition of peak acid output rates at28%, 62%, and 90% for the 5, 10, and 20-mg/day dosages respectively, in healthy volunteers at the end of 5 days(19). With a plasma half-life of 1–1.5 hours, and 97% plasma protein-bound (18), Esomeprazole has a lower intrinsic clearance rate due to its minimal first-pass metabolism, less hydroxylation via CYP2C19,(18) thus maintaining the peak levels in the body for a longer period. This pharmacodynamic uniqueness, taken together, accounts for the better clinical efficacy of this drug when compared with its predecessors.

Clinical uses of esomeprazole in GERD

Reduction of gastric acidity- Cumulative evidence from studies has concluded that Esomeprazole maintains intragastric pH at a higher level and above 4 for a longer period than other PPIs (20) . This forms the basis of its exceptional capability to reduce acidity as has been resonated in studies by Lind et al, Ross et al, Miner et al and Johnson et al (20).

Reduction of esophageal acidity-Low nocturnal intragastric pH correlates with high nocturnal intraesophageal acid reflux. A study by RW Yeh and associates revealed that Esomeprazole, when administered at high doses, was associated with the significant breakthrough of intraesophageal acid control, particularly at night in a patient suffering from chronic GERD (21). Yet another study (22) by Schmitt C et al, noted that healing rates with Esomeprazole were significantly higher than those with omeprazole at weeks 4 (60.8% vs 47.9%; P = 0.02) and 8(88.4% vs 77.5%; P = 0.007) in patients with moderate to severe erosive esophagitis.

Healing of erosive GERD- A notable study by Kahrilas et al. (12) among 1960 patients with erosive GERD, has shown that Esomeprazole magnesium 20 and 40 mg were superior to omeprazole 20 mg for healing at eight weeks. The researchers further noted that safety and tolerability with Esomeprazole were equivalent to omeprazole. Addressing the issue of resolution of GERD-associated symptoms, accumulating evidence suggests that Esomeprazole 40 mg od is more effective than omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg (23,24,25).

Maintenance therapy of healed erosive GERD-With a high relapse rate of 26–48% following discontinuation of PPIs(26), most GERD patients need to follow lifelong drug therapy. A study by Johnson et al (27) demonstrated that in patients with healed esophagitis, healing was maintained in 93.6% of patients treated with Esomeprazole 40 mg, 93.2% treated with Esomeprazole 20 mg, and 57.1% treated with Esomeprazole 10 mg, against only 29.1% treated with placebo, even after 6 months.

Improves health-related quality of life-GERD along with its associated symptoms can be very detrimental to the physical as well as the mental well-being of a patient. Studies assessing the health-related QoL have concluded that within 2 weeks, after treatment with Esomeprazole in GERD patients, both symptoms and QoL improved in all subscales. (28) Similar findings were reported by Pace et al, who opined that esomeprazole 40 mg OD, when given in non-erosive and mild erosive GERD, for 4 weeks, led to profound improvements in QoL indices (20).

Indications and formulary recommendations

Esomeprazole magnesium is currently indicated in FDA-approved labelling for use in the treatment of symptomatic GERD (20 mg once daily for 4 weeks; maximum, 8 weeks), including use for healing (20 or 40 mg once daily for 4–8 weeks; maximum, 16 weeks) and maintenance of healing (20 mg once daily; studies of maintenance therapy for six months exist) in erosive esophagitis. (29)

Available as an enteric-coated delayed-release capsule, esomeprazole is advocated to be taken at least one hour before a meal (29). Studies have affirmed that esomeprazole dosage adjustments are not recommended for elderly patients (30) or patients with mild to moderate renal insufficiency, while at the same time highlighting that patients with severe hepatic insufficiency should not receive esomeprazole dosages greater than 20 mg once daily.

Conclusion

The advent of esomeprazole has brought a revolution in the current treatment protocols of GERD. As evidence grows supporting the unmatched efficacy of this drug, not only in acid suppression but also in ameliorating the associated symptoms of GERD, the novel advantages provided by esomeprazole continue to unravel. The medical fraternity looks forward to more future studies to establish the unanimous superiority of this drug among all other concurrent PPIs used today to manage GERD.

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