Managing Night Time GERD: Comparative Review of Efficacy of esomeprazole against conventional PPIs

Written By :  Dr. Shubham Vatsya
Medically Reviewed By :  Dr. Kamal Kant Kohli
Published On 2021-10-25 07:15 GMT   |   Update On 2021-10-27 06:26 GMT

Night-time Gastroesophageal reflux disease (GERD) causing symptoms is now being identified as a distinct clinical entity (1). It is an under-appreciated problem with a high risk of developing esophagitis and stricture, as well as adenocarcinoma of the esophagus. (2) Extensively documented to affect the life quality of patients adversely (2,3) due to nocturnal acid reflux, heartburn, and sleeplessness, night-time GERD, if not managed efficiently, can lead to severe detrimental outcomes.

Proton Pump Inhibitors (PPI) are the first choice drugs for treating GERD, along with its associated symptoms. (4,5) While traditional PPIs like Lansoprazole, Omeprazole, Pantoprazole have been in use for a long time, recent studies have highlighted that their use comes with their limitations and side effects. (6, 7)

Esomeprazole, a relatively newer PPI, has been introduced as the first PPI with a single active optical isomer, making it more efficacious in acid suppression and thus, combating GERD. Esomeprazole is metabolically more stable and leads to higher bioavailability and an increase in the area under the plasma concentration-time curve (AUC). Hence, it provides more effective control over gastric acid secretions, when compared to other PPI therapy. Differing from its predecessor Omeprazole by virtue of its novel molecular construction, growing evidence suggests this drug has an edge over other available PPIs in combating GERD. (8, 9)

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Is Esomeprazole better than traditional PPIs?

Managing nighttime GERD- Exhibiting clear supremacy in controlling esophageal and gastric acid secretions than other PPIs (10), Esomeprazole is a more potent drug in managing nocturnal GERD.

  • Esomeprazole vs lansoprazole- Shedding light on the efficacy and activity of esomeprazole on intra-esophageal pH profiles when compared to PPIs, a study compared 40 mg of esomeprazole to 30 mg of lansoprazole in 30 patients with complicated GERD. (11) Results indicated that esomeprazole was superior to lansoprazole in both total (75% vs. 28%, P = 0.026) and supine position (93% vs. 50%, P=0.012) nocturnal esophageal acid exposure. Another study by Schmitt C et al noted that esomeprazole was superior to lansoprazole at 4 weeks (60.8% vs. 47.9%,P = 0.02) and 8 weeks (88.4% vs. 77.5%, P = 0.007) in patients with moderate to severe esophagitis(12) .Yet other trials have compared the effects of esomeprazole with other PPIs in erosive GERD, analyzing healing rates and GERD symptoms. The authors concluded that Esomeprazole (40 mg) exhibited a higher healing rate and was more effective than lansoprazole (30 mg) in resolving heartburn. (13)
  • Esomeprazole vs Omeprazole- Affirming the superiority of esomeprazole, notable studies by Kahrilas PJ and Richter JE, indicated that esomeprazole had a higher healing rate and better symptom control than omeprazole in mild reflux esophagitis. (14,15) Research has further confirmed that esomeprazole holds its exceptional efficacy even in more severe esophagitis. (16)
  • Esomeprazole vs pantoprazole- Studies comparing esomeprazole 40 mg with pantoprazole 40 mg and aimed at evaluating the healing in erosive oesophagitis concluded that esomeprazole had higher healing rates than pantoprazole at 4 weeks (81% vs. 75%) and 8 weeks (96% vs. 92%) and provided better resolution of GERD symptoms. (8,17)

Maintenance therapy of healed erosive GERD- Sustaining a symptomless and healed state after successful resolution of nocturnal GERD is as important as managing an acute episode.

  • Esomeprazole vs. lansoprazole- Noteworthy studies by Devault et al and Lauritsen et al, aimed at evaluating the healing rate of erosive GERD at 6 months opined that esomeprazole was far more competent than lansoprazole with 84.8% vs. 75.9% and 83% vs. 74% patients healed of symptoms, respectively. (18) Esomeprazole (20 mg) was more effective in maintaining therapy than lansoprazole (15 mg) at 6 months, with endoscopy-confirmed healing (19). A similar second study found 83% of the esomeprazole group was in remission compared to 74% of the lansoprazole group, at 6 months, and more patients were symptom-free. (20)
  • Esomeprazole vs. pantoprazole- Maintaining a healed state in erosive esophagitis for a longer period, along with relief of gastroesophageal symptoms, studies have affirmed that esomeprazole is superior to pantoprazole. (21) Heartburn relapse rates after esophagitis were also lower with esomeprazole.

Managing relapsing GERD- With a strikingly high relapse rate of 80 %, patients with severe erosive GERD, very often, revert to a compromised life within 12 months of discontinuing PPI therapy. (22) Such complicated scenarios warrant choosing a better PPI with a proven high success rate. A remarkable study by Jones et al, investigating the effectiveness of esomeprazole 40 mg in GERD symptoms persisting in patients even after receiving a full daily dose PPI, has concluded that treatment with esomeprazole 40 mg daily in such patients is associated with a significant reduction in symptoms within 4–8 weeks., both in frequency and severity. (23)

On-demand therapy- Esomeprazole (20 mg), as an on-demand therapy, was found to be economically and potentially more effective than lansoprazole 15 mg daily after 6 months in endoscopy-negative GERD. (24) The study further showed better symptom control with more patients willing to continue on-demand therapy than using lansoprazole on daily basis (93% vs. 88%).

Cost effectiveness-The success of on-demand therapy with esomeprazole resonates with the fact that treating GERD with this drug can lead to direct cost savings as against a continuous treatment with other PPIs. Further, considering the average wholesale prices, esomeprazole is priced at par with the other PPIs. (25)

Safety-Classified as a class B drug, esomeprazole is generally well-tolerated and regarded to be effective and safe during pregnancy. (10) Reproductive studies in animals have found no evidence of impaired fertility or harm to the fetus in subjects receiving the equivalent of or up to 57 times the human dosage. (25)

Though long-term or high-dose PPI therapy increases the risk of hip fracture, (26), the relationship between esomeprazole, fracture risk, and osteoporosis remains inconclusive.

Key pointers 

A decent knowledge of esomeprazole can go a long way in changing the scenario of treating nighttime GERD.

Esomeprazole maintains an intragastric PH above 4 for a longer time than other PPIs.

Esomeprazole 40 mg od for up to 8 weeks provided higher rates of healing of erosive GERD and a greater proportion of patients with sustained resolution of heartburn than omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg od.

Esomeprazole 20 mg od has also been shown to be more effective in maintaining healing of erosive GERD compared with lansoprazole 15 mg od or pantoprazole 20 mg od.

Conclusion-

Esmoprazole, a first-of-its-kind PPI, has revolutionized the management protocols for night-time GERD. Physicians should be aware of the new advances on this drug as research continues to reaffirm its supremacy. With more robust evidence supporting its potency in GERD, esomeprazole has cemented its position as the first choice over other available PPIs.

References:

1. Shaker R, Castell DO, Schoenfeld PS, Spechler SJ. Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association. Am J Gastroenterol. 2003 Jul;98(7):1487-93. doi: 10.1111/j.1572-0241.2003.07531.x. PMID: 12873567.

2. Clarrett, D. M., & Hachem, C. (2018). Gastroesophageal Reflux Disease (GERD). Missouri medicine, 115(3), 214–218.

3. Sandhu, D. S., & Fass, R. (2018). Current Trends in the Management of Gastroesophageal Reflux Disease. Gut and liver, 12(1), 7–16. https://doi.org/10.5009/gnl16615

4. Scholten T. (2007). Long-term management of gastroesophageal reflux disease with pantoprazole. Therapeutics and clinical risk management, 3(2), 231–243. https://doi.org/10.2147/tcrm.2007.3.2.231

5. Scarpignato, C., Gatta, L., Zullo, A. et al. Effective and safe proton pump inhibitor therapy in acid-related diseases – A position paper addressing benefits and potential harms of acid suppression. BMC Med 14, 179 (2016). https://doi.org/10.1186/s12916-016-0718-z

6. Abbas, M. K., Zaidi, A., Robert, C. A., Thiha, S., & Malik, B. H. (2019). The Safety of Long-term Daily Usage of a Proton Pump Inhibitor: A Literature Review. Cureus, 11(9), e5563. https://doi.org/10.7759/cureus.5563

7. Calabrese, C., Fabbri, A., & Di Febo, G. (2007). Long-term management of GERD in the elderly with pantoprazole. Clinical interventions in aging, 2(1), 85–92. https://doi.org/10.2147/ciia.2007.2.1.85

8. Kalaitzakis, E., & Björnsson, E. (2007). A review of esomeprazole in the treatment of gastroesophageal reflux disease (GERD). Therapeutics and clinical risk management, 3(4), 653–663.

9. Çelebi A, Aydın D, Kocaman O, Konduk BT, Şentürk Ö, Hülagü S. Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastrıc pH in extensive metabolizer patients with gastroesophageal reflux disease. Turk J Gastroenterol. 2016 Sep;27(5):408-414. doi: 10.5152/tjg.2016.15514. PMID: 27782887.

10. Gastric Acid-Related Diseases: Focus on Esomeprazole, B. Al-Judaibi, N. Chande, G.K.Dresser, first published May4,2010;https://doi.org/10.4137/CMT.S4500

11. Frazzoni M, Manno M, De Micheli E, Savarino V. Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole. Dig Liver Dis. 2006 Feb;38(2):85–90.

12. Schmitt C, Lightdale CJ, Hwang C, Hamelin B. A multicenter, randomized, double-blind, 8-week comparative trial of standard doses of esomeprazole(40 mg) and omeprazole (20 mg) for the treatment of erosive esophagitis.Dig Dis Sci. 2006 May;51(5):844–50.

13. Castell DO, Kahrilas PJ, Richter JE, Vakil NB, Johnson DA, Zuckerman S, et al. Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis. Am J Gastroenterol. 2002 Mar;97(3):575–83.

14. Kahrilas PJ, Falk GW, Johnson DA, Schmitt C, Collins DW, Whipple J, et al. Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators. Aliment Pharmacol Ther 2000 Oct;14(10):1249–58.

15. Richter JE, Kahrilas PJ, Johanson J, Maton P, Breiter JR, Hwang C, et al.Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. Am J Gastroenterol. 2001 Mar;96(3):656–65.

16. Fennerty MB, Johanson JF, Hwang C, Sostek M. Efficacy of esomeprazole 40 mg vs. lansoprazole 30 mg for healing moderate to severe erosive oesophagitis. Aliment Pharmacol Ther. 2005 Feb 15;21(4):455–63.

17. Labenz J, Armstrong D, Lauritsen K, Katelaris P, Schmidt S, Schutze K,et al. A randomized comparative study of esomeprazole 40 mg versus pantoprazole 40 mg for healing erosive oesophagitis: the EXPO study. Aliment Pharmacol Ther. 2005 Mar 15;21(6):739–46.

18. Gastric Acid-Related Diseases: Focus on Esomeprazole, B. Al-Judaibi, N. Chande, G.K.Dresser,FirstPublished May4,2010 ;https://doi.org/10.4137/CMT.S4500

19. Devault KR, Johanson JF, Johnson DA, Liu S, Sostek MB. Maintenance of healed erosive esophagitis: a randomized six-month comparison of esomeprazole twenty milligrams with lansoprazole fifteen milligrams. Clin Gastroenterol Hepatol. 2006 Jul;4(7):852–9.

20. Lauritsen K, Deviere J, Bigard MA, Bayerdorffer E, Mozsik G, Murray F, et al. Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results. Aliment Pharmacol Ther. 2003 Feb;17(3):333–41

21. Goh KL, Benamouzig R, Sander P, Schwan T. Efficacy of pantoprazole 20mg daily compared with esomeprazole 20mg daily in the maintenance of healed gastroesophageal reflux disease: a randomized, double-blind comparative trial—the EMANCIPATE study. Eur J Gastroenterol Hepatol. 2007 Mar;19(3):205–11.

22. Hetzel DJ, Dent J, Reed WD, Narielvala FM, Mackinnon M, McCarthy JH, et al. Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology. 1988 Oct;95(4):903–12.

23. Jones R, Patrikios T. The effectiveness of esomeprazole 40 mg in patients with persistent symptoms of gastro-oesophageal reflux disease following treatment with a full dose proton pump inhibitor. Int J Clin Pract. 2008 Dec;62(12):1844-50. doi: 10.1111/j.1742-1241.2008.01923.x. Erratum in: Int J Clin Pract. 2009 Jun;63(6):977. PMID: 19166433; PMCID: PMC2680259.

24. Tsai HH, Chapman R, Shepherd A, McKeith D, Anderson M, Vearer D, et al. Esomeprazole 20 mg on-demand is more acceptable to patients than continuous lansoprazole 15 mg in the long-term maintenance of endoscopy-negative gastro-oesophageal reflux patients: the COMMAND Study. Aliment Pharmacol Ther. 2004 Sep 15;20(6):657–65.

25. Johnson TJ, Hedge DD. Esomeprazole: a clinical review. Am J Health Syst Pharm. 2002 Jul 15;59(14):1333-9. doi: 10.1093/ajhp/59.14.1333. PMID: 12132559.

26. Nexium (esomeprazole magnesium) delayed-release capsules package insert. Wilmington, DE: AstraZeneca; 2001.

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