(A-276) Regional trends of opioid epidemic using safety signal of drug misuse and dependence: a disproportionality analysis using Vigibase

Background: The opioid epidemic, which has progressed through three waves and was initially a major issue in the United States, has become a global concern, affecting regions such as Europe and the Asia-Pacific. Using pharmacovigilance data from VigiBase, we conducted a regional comparison of opioid-related adverse event reporting.

Objectives: To detect and compare signals of opioid misuse and dependence across three waves of opioid epidemic and regions.

Methods: We used VigiBase, a world-wide pharmacovigilance database containing adverse drug reactions with more than 40 million Individual Case Safety Reports (ICSRs) from 150 different countries. The primary drugs of interest were oxycodone and fentanyl, while morphine and tramadol, two commonly prescribed opioid analgesics, served as comparator drugs. We defined the adverse event (AE) of interest as “misuse and dependence” according to Standardized MedDRA Query criteria, and analyzed data from three epidemic waves (1st: 1990-2009, 2nd: 2010-2012, 3rd: 2013-2024) and three regions (Americas, Western Pacific, and Europe) to identify period and regional signals. To assess safety signals, we calculated the reporting odds ratio (ROR) for "misuse AEs" across epidemic waves. Safety signals were defined as cases with Opioid-AE ROR > 2, if chi-squared > 4, and if the number of reports > 3.

Results: The first wave of the opioid epidemic (1990–2010) peaked in 2005 with 8,402 ICSRs for oxycodone. The second wave (2010–2012) peaked in 2011 with 10,444 ICSRs for oxycodone and 11,451 for fentanyl. The third wave, ongoing since 2013, peaked in 2021 for oxycodone (n=45,025) and in 2017 for fentanyl (n=32,704), followed by a decline through 2024. The safety signals for oxycodone were found across all opioid epidemic waves in region of Americas (1st ROR: 4.40, χ2 > 4, No. of cases(n): 9,102, 2nd ROR: 2.13, χ2 > 4, n: 2,299, 3rd wave ROR: 5.20, χ2 > 4, n: 108,068), and two waves in Western Pacific region (2nd ROR: 6.53, χ2 > 4, n: 81, 3rd ROR: 5.94, χ2 >4 n = 1,066). In contrast, no safety signals for oxycodone were found in the European region (1st ROR: 1.72, χ2 > 4, n = 3, 2nd ROR: 1.24, χ2 = 1.4, n= 43, 3rd ROR: 0.63, χ2 >, n= 308). For fentanyl, no safety signals were identified across all three waves in any region.

Conclusions: Oxycodone misuse and dependence signals were detected in all three waves in the Americas and two waves in the Western Pacific. The high misuse and dependence in the Western Pacific may lead to an opioid epidemic. Findings on the lack of signals in Europe and for fentanyl across regions suggests under-reporting of illicit opioid use. These limitations underscore the need for further research on opioid misuse, especially involving illicit opioids.