Are polypharmacy side effects predicted by public data still valid in real-world data?
Gaeun Kee,
Hee Jun Kang,
Imjin Ahn,
Hansle Gwon,
Yunha Kim,
Hyeram Seo,
Heejung Choi,
Ha Na Cho,
Minkyoung Kim,
JiYe Han,
Seohyun Park,
Kyuwoong Kim,
Tae Joon Jun,
Young-Hak Kim
Affiliations
Gaeun Kee
Department of Information Medicine, Asan Medical Center, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Hee Jun Kang
Division of Cardiology, Asan Medical Center, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Imjin Ahn
Department of Information Medicine, Asan Medical Center, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Hansle Gwon
Department of Information Medicine, Asan Medical Center, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Yunha Kim
Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Hyeram Seo
Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Heejung Choi
Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Ha Na Cho
Department of Information Medicine, Asan Medical Center, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Minkyoung Kim
Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
JiYe Han
Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Seohyun Park
Department of Information Medicine, Asan Medical Center, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea
Kyuwoong Kim
National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, 10408, Goyang, Republic of Korea
Tae Joon Jun
Big Data Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea; Corresponding authors.
Young-Hak Kim
Division of Cardiology, Department of Information Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympicro 43gil, Songpagu, 05505, Seoul, Republic of Korea; Corresponding authors.
Background and Objective: Although interest in predicting drug-drug interactions is growing, many predictions are not verified by real-world data. This study aimed to confirm whether predicted polypharmacy side effects using public data also occur in data from actual patients. Methods: We utilized a deep learning-based polypharmacy side effects prediction model to identify cefpodoxime-chlorpheniramine-lung edema combination with a high prediction score and a significant patient population. The retrospective study analyzed patients over 18 years old who were admitted to the Asan medical center between January 2000 and December 2020 and took cefpodoxime or chlorpheniramine orally. The three groups, cefpodoxime-treated, chlorpheniramine-treated, and cefpodoxime & chlorpheniramine-treated were compared using inverse probability of treatment weighting (IPTW) to balance them. Differences between the three groups were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Results: The study population comprised 54,043 patients with a history of taking cefpodoxime, 203,897 patients with a history of taking chlorpheniramine, and 1,628 patients with a history of taking cefpodoxime and chlorpheniramine simultaneously. After adjustment, the 1-year cumulative incidence of lung edema in the patient group that took cefpodoxime and chlorpheniramine simultaneously was significantly higher than in the patient groups that took cefpodoxime or chlorpheniramine only (p=0.001). Patients taking cefpodoxime and chlorpheniramine together had an increased risk of lung edema compared to those taking cefpodoxime alone [hazard ratio (HR) 2.10, 95% CI 1.26–3.52, p<0.005] and those taking chlorpheniramine alone, which also increased the risk of lung edema (HR 1.64, 95% CI 0.99-2.69, p=0.05). Conclusions: Validation of polypharmacy side effect predictions with real-world data can aid patient and clinician decision-making before conducting randomized controlled trials. Simultaneous use of cefpodoxime and chlorpheniramine was associated with a higher long-term risk of lung edema compared to the use of cefpodoxime or chlorpheniramine alone.
