EQUINE VETERINARY EDUCATION Equine vet. Educ. (2019) 31 (8) 441-446 doi: 10.1111/eve.12894


Hypothesis Article


Courses for horses: Rethinking the use of proton pump inhibitors in the treatment of equine gastric ulcer syndrome


B. W. Sykes†‡§ †School of Veterinary Sciences, The University of Queensland, Gatton, Queensland; ‡Bova Compounding, Caringbah, New South Wales, and §Luoda Pharma Pty Ltd, Caringbah, New South Wales, Australia Corresponding author email: b.sykes@uq.edu.au


Keywords: horse; stomach; ulcer; treatment; omeprazole; esomeprazole


Summary Oral omeprazole has been the cornerstone of equine gastric ulcer syndrome (EGUS) treatment for nearly 20 years. However, approximately 15–30% of equine squamous gastric disease (ESGD) cases and 75% of equine glandular gastric disease (EGGD) cases fail to heal within current treatment guidelines. Recently, a number of factors that may affect the efficacy of oral omeprazole have been highlighted and the pharmacodynamics of a number of novel proton pump inhibitors (PPIs) have been described in the horse. The purpose of this article is to review the factors that affect oral omeprazole efficacy, with the goal of maximising therapeutic response, and the novel PPIs recently described.


Introduction


It has been reported that the prevalence of squamous and glandular gastric disease are unrelated to each other (Murray et al. 2001; Luthersson et al. 2009a) and it has been shown that the risk factors for glandular disease are different from those for squamous disease (Habershon-Butcher et al. 2012). This suggests that they are separate, distinct disease entities and the European College of Equine Internal Medicine (ECEIM) consensus statement recently sought to clarify the terminology recognising that within the umbrella term of equine gastric ulcer syndrome (EGUS) numerous disease entities exist, with equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD) the most common conditions in the adult horse (Sykes et al. 2015a). Regardless of the cause of disease, acid suppressive


therapy is considered a cornerstone of treatment. The current ECEIM consensus statement recommendations reflect this, and oral omeprazole is currently considered the drug of choice (Sykes et al. 2015a). However, despite its widespread use, until recently little attention has been given to the factors that affect efficacy of oral omeprazole, or the management of refractory cases. The purpose of this article is to review these factors with specific focus on the role that diet and individual dose responsiveness play. Further, the author proposes that the use of individually tailored treatment plans that take into account the individual’s dietary conditions and individual dose responsiveness should be considered in lieu of the current blanket dosing recommendations for treatment and prevention of EGUS.


Disclaimer: Unregistered medications and off-label dosing discussed in the current manuscript should be used in accordance with local regulatory frameworks and best practice guidelines.


Equine squamous gastric disease (ESGD)


The pathogenesis of ESGD is well described with acid injury to the squamous mucosa, which has limited defence mechanisms and is not normally exposed to a pH of <4, considered the primary factor in disease development (Sykes et al. 2015a). Hydrochloric acid is the dominant factor, but volatile fatty acids produced locally in the stomach associated with grain feeding are also considered important contributors to disease (Vatistas et al. 1999; Frank et al. 2005; Luthersson et al. 2009b). Exercise, and the associated increase in intra-abdominal pressure that results in disruption


of gastric pH stratification and ‘splashing’ of highly acidic fluid from the ventral stomach onto the squamous mucosa, is also considered a key factor (Lorenzo-Figueras and Merritt 2002). Inhibition of acid production, and the consequent


increase in intragastric pH, results in healing of ESGD in the majority of patients with healing rates of 70–85% over a 4- week treatment duration consistently reported in the literature with once daily administration of oral omeprazole (Andrews et al. 1999; MacAllister et al. 1999; Lester et al. 2005; Sykes et al. 2015b). However, to date, little attention has been paid to the 15–30% of ESGD cases that fail to heal completely within this time period. Whether these cases represent the failure to address risk factors such as diet and exercise in clinical studies, or sub-therapeutic responses to oral omeprazole is unclear. In an early study, a 100% healing rate for ESGD was reported over a 3-week period in clinical cases, without dietary management (Murray et al. 1999), suggesting that if adequate acid suppression is achieved healing will occur regardless of the ongoing presence of dietary and exercise risk factors. This is further supported by the 100% healing observed over a 2- week period following the administration of a novel, long- acting, injectable omeprazole formulation that has been shown to be a potent inhibitor of acid production (Sykes et al. 2017a). Considering this, it is the author’s opinion that the persistence of ESGD lesions after 3 weeks of oral omeprazole is an indicator of sub-therapeutic acid suppression, rather than the contribution of other co- founding risk factors such as diet, exercise and changes in bacterial populations that have been proposed as contributory factors (Vatistas et al. 1999; Lorenzo-Figueras and Merritt 2002; Frank et al. 2005; Al Jassim et al. 2008; Luthersson et al. 2009b). This is consistent with the ‘no acid, no ulcer’ mantra (Malfertheiner et al. 2009) in human medicine.


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