Mee Yeon Lee,1 Suhyun Lee,1 Kyu-Nam Heo,1 Woo-Youn Kim,1 Sun Hoi Jung,2 Young-Mi Ah,3 Ju-Yeun Lee1 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 2Department of Pharmacy, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 3College of Pharmacy, Yeungnam University, Gyeongsan-si, Republic of KoreaCorrespondence: Ju-Yeun Lee, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea, Tel +82-2-3668-7472, Email jypharm@snu.ac.krPurpose: The use of proton pump inhibitors (PPI) is recommended to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) complications. The incidence of several adverse effects during the long-term use of PPI prompts the search for other alternatives. Limited studies have evaluated the efficacy of rebamipide, a widely used mucoprotective drug, as a gastroprotective agent (GPA) compared to PPI, focusing on the elderly chronic NSAID users, nor with GI risk stratification. We aimed to determine the population who would get benefit from the use of rebamipide as an alternative to PPI to prevent traditional nonsteroidal anti-inflammatory drug (tNSAID)-associated GI complications.Patients and Methods: We identified 41,889 and 35,708 elderly chronic tNSAID users with PPI and rebamipide co-therapy, respectively, from the national claims database. Outcome was defined as hospitalization or emergency department visits due to serious GI complications. Propensity score-matched cohorts were constructed and compared within risk strata.Results: In high and moderate risk groups with two risk factors, rebamipide showed a higher risk of serious GI complication compared to PPI (aHR 2.63, 95% CI 1.24– 5.59 and aHR 2.42, 95% CI 1.21– 4.83, respectively). However, in elderly patients without risk factors, there was no significant difference in the risk of serious GI complications between PPI and rebamipide (aHR 0.69, 95% CI 0.27– 1.76).Conclusion: This study suggested that rebamipide can be considered as an alternative to PPI in elderly chronic tNSAID users without risk factors. However, elderly patients with other risk factors should use PPI rather than rebamipide. Therefore, the presence of GI risk factors needs to be evaluated in elderly chronic tNSAID users to prescribe the most suitable GPA in clinical practice.Keywords: aged, gastroprotective agent, nonsteroidal anti-inflammatory drug, rebamipide, risk group
