Equine glandular gastric disease (EGGD) is a highly prevalent condition in performance horses (Hepburn and Proudman 2014; Sykes et al, 2015a). Studies have detailed the prevalence of EGGD across a variety of equestrian disciplines and horse populations:, reporting a prevalence of 47–65% in thoroughbred racehorses (Begg and O'Sullivan 2003; Sykes et al, 2015); 16–35% in endurance horses (Nieto et al, 2004; Tamzali et al, 2011) and 54–57% in leisure horses (Husted et al, 2009; Luthersson et al, 2009; Malmkvist et al, 2012). While acid injury is not thought to initiate EGGD, acid suppression appears to be an important factor in healing these lesions (Sykes et al, 2015a).
Proton pump inhibitors are the mainstay of gastric acid suppression in both human and veterinary medicine. Omeprazole is the only proton pump inhibitor authorised for use in horses and while oral omeprazole results in squamous healing rates of over 70% (Murray et al, 1997; Andrews et al, 1999; Doucet et al, 2003; Lester et al, 2005), it is considered ineffective as monotherapy in the treatment of glandular lesions (Rendle et al, 2018).
A recent consensus paper by Rendle et al (2018) outlined three first-line options for the treatment of glandular disease:
- Oral omeprazole and sucralfate
- Misoprostol
- Long-acting injectable omeprazole.
The highest rates of healing have been reported following the use of long-acting injectable omeprazole (Sykes et al, 2017a; Gough et al, 2019). Reported rates of healing following 4 weeks of oral omeprazole and sucralfate therapy are between 20% and 67.5% and this variation is likely a result of differing definitions of healing between authors (Hepburn and Proudman, 2014; Varley et al, 2019). This combination also presents practical challenges for owners regarding the administration of both medications at different times on an empty stomach. Misoprostol has been reported to result in healing of EGGD in 55–72% cases (Varley et al, 2019; Pickles et al, 2020). However, one study reported that in 42% of cases treated with misoprostol, squamous disease either developed or worsened (Pickles et al, 2020). Furthermore, misoprostol tablets (Cytotec, Pfizer) are increasingly difficult to source and the human health safety concerns must also be considered. Given the lack of robust evidence to support the use of oral omeprazole or misoprostol in the treatment of EGGD, alternative oral preparations should be investigated.
In human medicine newer proton pump inhibitors have been developed, including pantoprazole, rabeprazole and most recently, esomeprazole (Andersson et al, 2001; Kendall, 2003; Gralnek et al, 2006). Esomeprazole is the S-isomer of omeprazole, which results in more pronounced and consistent acid suppressive effects compared to omeprazole in humans (Lind et al, 2000; Rohss et al, 2001). Evidence to support its use in the treatment of glandular disease is lacking, although esomeprazole has been associated with the healing of both squamous and glandular lesions in 80% of horses that failed to respond to oral omeprazole monotherapy (Rendle, 2017). Given its widespread use in the treatment of peptic ulcer disease in humans (Lenoir et al, 2019; Madi et al, 2019; Thompson, 2019) and the limited efficacy of other oral preparations available for horses, esomeprazole warrants further investigation as an alternative treatment option for EGGD.
The objective of this study was to conduct a retrospective evaluation of EGGD cases treated with esomeprazole. To the author's knowledge, there are no published reports detailing the effectiveness of oral esomeprazole as a first-line treatment option for clinical cases of glandular gastric disease.
Methods
Horses
Medical records and gastroscopy images from horses examined between July 2020 and May 2021 by Avon Ridge Equine Veterinary Services were reviewed. Horses diagnosed with EGGD and treated first-line with oral esomeprazole at 4 mg/kg were identified and included in the study.
Medication
The esomeprazole used was a compounded oral paste containing enteric coated esomeprazole granules (100mg/ml; Bova Aus, Caringbah, New South Wales, Australia).
Gastroscopy
Following sedation with 0.01mg/kg detomidine hydrochloride (10mg/ml; Dozadine, Virbac Pty Ltd, Sydney, Australia), gastroscopy was performed using a 3.3 m flexible gastroscope (Endo I: Steris, Mentor, Ohio, USA) to visualise the squamous mucosa as well as the glandular mucosa at the level of the margo plicatus and pyloric antrum. The presence of residual fluid in the stomach of all horses obscured the observation of the most ventral portion of the glandular mucosa. Gastroscopy was then repeated within 0–3 days, following the discontinuation of treatment to assess endoscopic response.
Client Communication
Owners were advised to administer esomeprazole paste in the morning, following an overnight fast and at least 30–60 minutes before feeding. A standard advice sheet was emailed to owners following the gastroscopy procedure to outline management changes including reducing the frequency of exercise to 4 days per week, minimising the number of riders and handlers, and identifying stressors for each individual horse.
Upon follow-up gastroscopy, owners reported that they had complied with medication advice and had made attempts to reduce stressors, but all horses were maintained in their current workload.
Results
A total of seven horses met the criteria for inclusion, including two Thoroughbreds, one Arabian X, one Welsh Pony, one Riding Pony, one Standardbred and one Warmblood. There were three geldings and four mares, with ages ranging from 8–23 years old. Out of seven horses, four were treated for 28 days and three were treated for 14 days.
Upon follow-up gastroscopy for the four horses treated with esomeprazole for 28 days, glandular lesions were healed in three horses (75%) and one horse (25%) showed no improvement.
Table 1. Case details of horses included in the study
| Case | Signalment | Lesion Type | Location | Treatment Duration | Result |
|---|---|---|---|---|---|
| 1 | 13-year-old Thoroughbred, mare | Raised, fibrino-suppurative | Pyloric antrum | 28 days | Healed (Figure 1) |
| 2 | 23-year-old Thoroughbred, gelding | Flat, erythematous | Pyloric antrum | 28 days | No improvement |
| 3 | 16-year-old Warmblood X, mare | Flat, erythematous | Pyloric antrum | 28 days | Healed |
| 4 | 8-year-old Warmblood, gelding | Raised, haemorrhagic | Pyloric antrum | 28 days | Healed (Figure 2) |
| 5 | 6-year-old Welsh Pony, mare | Flat, erythematous | Fundus | 14 days | Healed (Figure 3) |
| 6 | 13-year-old Riding Pony, mare | Flat, erythematous | Fundus | 14 days | Healed |
| 7 | 11-year-old Standardbred, gelding | Flat, erythematous | Pyloric Antrum | 14 days | No improvement |
On follow-up gastroscopy for the three horses treated with esomperazole for 14 days, glandular lesions were healed in two horses (67%) and in one horse (33%) there was no improvement.
The owners declined further treatment in cases 2 and 7, both of which showed no improvement following 28 and 14 days of esomeprazole, respectively.
Discussion
The healing of 75% and 67% of horses with equine glandular gastric disease treated with 28 and 14 days of esomeprazole, respectively, is attributed to the potent acid suppressive effects of esomeprazole. In human medicine, studies have shown that esomeprazole has a more rapid onset of action; is metabolised by the liver much more slowly and results in a three to four times higher area under the curve, compared to omeprazole (Andersson et al, 2001; Kendall, 2003). A higher plasma concentration allows more drug to enter the parietal cell to inhibit hydrochloric acid production. In horses, esomeprazole has also been demonstrated to be superior to omeprazole in its ability to increase gastric pH (Pereira et al, 2009; Videla et al, 2011; Sykes et al, 2017b).
The rate of healing following 28 days of treatment with esomeprazole is similar to rates reported using long-acting injectable omeprazole (Sykes et al, 2017a; Rendle et al, 2018), albeit in a much smaller number of horses. While there exists a growing body of evidence to suggest that long-acting injectable omeprazole is the most effective treatment option for EGGD (Sykes et al, 2017a; Gough et al, 2019, 2020), esomeprazole may provide a valid alternative for horses which are refractory to intramuscular injection or racehorses that cannot be treated with long-acting injectable omeprazole because of withdrawal times and rules of racing. The rates of healing observed in this study also compare very favourably with rates of healing for oral omeprazole and sucralfate (Hepburn and Proudman, 2014; Varley et al, 2019; Kranenburg et al, 2020). Treatment with esomeprazole is only required once daily, as opposed to three treatments required with an omeprazole and sucralfate combination. Therefore, esomeprazole is much easier for owners and handlers to administer regular and its use would likely be associated with higher levels of compliance.
Glandular gastric disease in horses shares similarities to peptic ulcer disease in humans (Sykes et al, 2015b) in that rates of healing are thought to be directly proportional to the length of time within a 24-hour period that the intra-gastric pH remains above level 4 (Lind et al, 2000). Duration of intra-day acid suppression is one of the factors which may account for the poor response of EGGD to oral omeprazole (Sykes et al, 2015c). In human studies, the percentage of a 24-hour period for which intragastric pH remained above level 4 was significantly higher for esomeprazole compared to omeprazole. A similar effect was also demonstrated in horses by Sykes et al (2017b) with enteric coated esomeprazole at 2 mg/kg maintaining pH>4 at the mucosal surface for 80% of a 24-hour period, compared to only 40% for oral omeprazole (Sykes et al, 2017). The increased efficacy is likely because of esomeprazole's lower first-pass hepatic metabolism, increased area under the curve and slower plasma clearance compared to omeprazole (Andersson et al, 2001). More robust clinical trials are required, but the data from this study suggests that esomeprazole as a monotherapy may be a viable treatment option for EGGD and combination with sucralfate, to further increase rates of healing, is a logical option which should be explored further.
The esomeprazole paste used in this study was formulated as an enteric coated preparation which may have favoured rates of healing despite any potential compliance issues. Studies have demonstrated superior bioavailability of enteric coated products compared to buffered or plain omeprazole (Birkmann et al, 2014; Sykes et al, 2016) and the absorption of coated preparations also appears to be less affected by feeding (Sykes et al, 2015c).
A minimum treatment duration of 28 days is recommended for the treatment of glandular disease (Sykes et al, 2015b; Rendle et al, 2018). However, owing to financial constraints, it was not possible to treat all horses for 28 days. Those cases which did heal after 14 days of treatment, had atypical lesions located in the fundus which may have affected the treatment outcomes. Anecdotally, these lesions appear to be more responsive to acid suppression and easier to treat compared to those located at the pyloric antrum.
The main limitation of this study was the small sample size and its retrospective nature. A second limitation of this study was that all horses were maintained at their full working regime, as exercise has been shown to be a risk factor (Sykes et al, 2019) for the development of glandular lesions and this may have negatively impacted treatment outcomes. However, it could be argued that this represents a more realistic scenario and good rates of healing were still achieved in this study, despite no reduction in exercise.
Conclusions
This study suggests that esomeprazole could be considered as a valid first-line treatment option for glandular gastric disease in horses. However, case numbers were low and the study was subject to a number of limitations. Larger, blinded, randomised clinical trials of esomeprazole are warranted.
KEY POINTS
- Equine glandular gastric disease is a highly prevalent condition for which there is no universally effective treatment.
- In this study, 75% (3/4) and 67% (2/3) of horses with equine glandular gastric disease healed following treatment with oral esomeprazole for 28 and 14 days, respectively.
- The study was limited by its small sample size and retrospective nature.
- Esomeprazole may be a valid first-line treatment option for equine glandular gastric disease and warrants further consideration.