Dear Editor,
We thank very much the Authors of this letter [Citation1], who emphasize the role of the mucoprotective agent rebamipide in protecting NSAID-induced upper and lower gastrointestinal complications. They state that PPIs are dangerous medications and, among their potential adverse events on many body organs, as recently reported in medical literature with added hyperbole, the frequent damage of the small bowel cannot be dismissed [Citation2]. So, the beneficial use of PPIs in healing and preventing the formation of NSAID-induced gastric ulcers, largely documented in many clinical trials and meta-analyses [Citation3–Citation5], can be associated with the increase of NSAID enteropathy, which seems to be due to gram-negative intestinal dysbiosis [Citation6]. The above Authors conclude that PPIs should not be administered to reduce the harm of NSAIDs on gastric mucosa and should be replaced by other agents, such as rebamipide, which has been shown to protect the whole gastroenteric mucosa [Citation1].
All these considerations, however, deal with the safety of PPIs and our recent review [Citation7] on the use and misuse of them in the clinical setting was intended as a deep analysis of their appropriate use and frequent misuse in the clinical setting and not as a detailed appraisal of their potential adverse events and of the means to contrast them.
We agree that NSAID enteropathy can be aggravated by concomitant PPI administration, as mentioned by the Authors of this letter [Citation1], but it must be borne in mind that this enteropathy, although common, often presents subclinically or is totally asymptomatic [Citation8].
Furthermore, the above Authors say that PPIs are not safe medicines, but this concept should be expressed with great caution. In fact, although many recent papers have highlighted a panoply of purported serious adverse effects associated with PPI use, including chronic kidney disease, cognitive decline, myocardial infarction, stroke, bone fracture, enteric infections and electrolyte abnormalities, other Authors have greatly questioned the reliability of these studies, which are primarily based on observational and retrospective findings [Citation9,Citation10]. They have inherent limitations because they were not designed to answer a specific question and information was not collected with a specific hypothesis in mind [Citation11]. Moreover, PPIs were not assigned at random, experimental, and control groups were not well matched, the grade of PPI exposure in terms of dose, duration, and date of initiation is unknown and, more importantly, unaccounted biases and confounding factors persist despite multivariable regression. Therefore, there is no doubt that PPIs are well tolerated and effective drugs for many and firmly established indications [Citation12,Citation13] and the quality of evidence linking them to a variety of adverse events is very low.
Finally, even though studies with rebamipide have shown that this compound is more effective than placebo in controlling occult bleeding and ulceration of the small bowel detected by means of capsule endoscopy, this medication is not available in western countries and, in addition, more well-designed clinical trials should be carried out to fully confirm the practical value of rebamipide [Citation14].
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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References
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