Letter: mucosal injury with exposure to low‐dose nonsteroidals

Abstract

Sirs, We read with interest the article by Hawkey et al., ‘Endoscopic evaluation of the gastro-duodenal tolerance of short-term analgesic treatment with 25 mg diclofenac-K liquid capsules’.1 The study evaluated the incidence of endoscopic gastroduodenal mucosal injury associated with 5 days of exposure to low/over the counter (OTC) doses of nonsteroidal anti-inflammatory drugs (NSAIDs): diclofenac-K liquid or diclofenac-K tablet (each at a total daily dose (TDD) of 75 mg), ASA (TDD of 3 g) or ibuprofen (TDD of 1.2 g). The authors highlight a significant and relatively understudied medical concern; most studies evaluate standard dose NSAIDs for the chronic treatment of inflammatory disorders and focus on endoscopic ulcer rates, tolerability, or bleeding outcomes.2, 3 For short-term low-dose/OTC medications, few studies have looked at such endpoints.4-6 The assumption has been that short courses of low-dose NSAIDs would be both tolerated and have a favourable safety profile. In conducting this study, the authors have attempted to directly compare the relative safety associated with diclofenac-K formulations as compared to comparable doses of ibuprofen or aspirin. The question that arises from this study is how do we accurately evaluate the clinically relevant safety of various medications used at OTC doses for short periods of time? Furthermore, with short exposure and low-dose, do variations in the incidence of erosions actually predict clinical safety? We believe that this may not be the best way to compare safety. Instead, the more clinically relevant endpoints would be to evaluate tolerability and persistence of use in a population who require short-term low-dose therapy. It would also be important to simultaneously measure the therapeutic efficacy for which the safer medication is being tested; as the authors point out, different formulations of medications may impact safety and tolerability differently. We congratulate the authors on highlighting the need to look at the safety of OTC nonsteroidals and look forward to future studies. Declaration of personal interests: Dr Goldstein has served as a speaker, a consultant and/or an advisory board member for Pfizer, Logical Therapeutics, Pozen, AstraZeneca, Takeda, Novartis, Astellas, Proctor and Gamble, and has received research funding from Pfizer, Sucampo, Pozen, Logical Therapeutics and AstraZeneca. Declaration of funding interests: None.