Opioid-Related Mortality for Individuals with Sickle Cell Disease Remains Low with No Significant Increase during 2013-2019
Authors: Mucalo Lana , Brandow Amanda M. , Singh Ashima 
Published: November 2021

Abstract
In 2017, the United States (US) Department of Health and Human Services declared the opioid epidemic a public health emergency due to rising opioid-related deaths. Since then, there has been increasing pressure to implement policies that regulate the use and prescribing of opioid medications. These new policies that include limiting the amount of prescribed opioids can adversely affect individuals with chronic pain conditions, such as sickle cell disease (SCD), who require opioid analgesics to manage acute and chronic pain. Individuals with SCD are also affected by racial disparities in healthcare which further exacerbate the withholding of opioid medication for these individuals when needed. Opioid-related mortality trends have not been quantified specifically for individuals with SCD. Therefore, the objective of this report is to describe opioid-related mortality trends in individuals with SCD. We hypothesize that there has been no significant increase in mortality rates due to opioids during the years 2013-2019 in individuals with SCD. Secondarily, we hypothesize that individuals with SCD do not have a higher rate of death due to opioids, compared to both Black people without SCD and White people.
To determine the number of deaths and population at risk during the years 2013-2019, we used data from the Center of Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) Multiple Cause of Death database. The opioid-related overdose deaths were identified using the underlying cause of death ICD-10 codes of 'X40', 'X41', 'X42', 'X43', 'X44', 'X60', 'X61', 'X62', 'X63', 'X64', 'X85', 'Y10', 'Y11', 'Y12', 'Y13', 'Y14' and multiple cause of death codes were used to identify specific drug type: 'T40.0', 'T40.1', 'T40.2', 'T40.3', 'T40.4', 'T40.6'. The deaths were determined to be among individuals with SCD if the multiple cause of death included codes for SCD 'D57.0', 'D57.1', 'D57.2', 'D57.4', 'D57.8'. Since there are no direct estimates of the SCD population in the US, we extrapolated the SCD population at risk by assuming that 1 in 365 Black people in the US have SCD. The mortality rates among Black people with SCD, Black people without SCD and White people were calculated as the crude rate per 100,000 people. The trends for death rates during 2013-2019 were evaluated using Joinpoint regression. These models fit the rates on a logarithmic scale using a series of permutation tests. We compared overall deaths over the years 2013-2019 between Black people with SCD, Black people without SCD and White people using the chi-square test in SPSS. A p-value of &lt;0.05 was considered significant.
Between 2013 and 2019 there were 273,301 recorded deaths due to opioids in the US. Of these, 236,982 (87.29%) occurred among White people, 31,316 (10.87%) among Black people without SCD, and 77 (0.03% of total opioid deaths) among Black people with SCD. Figure 1 represents mortality trends over time and Table 1 shows regression analysis and annual percentage changes in cohorts. We identified no statistically significant changes in the trend during the years 2013-2019 for Black people with SCD (annual percent change-APC=8.9%, p=0.217). However, we observe significant increasing opioid-related mortality rates for Black people without SCD (APC=24.9%, p&lt;0.001). The mortality rates for White people increased significantly until 2017 (APC=16.0%, p=0.011) and then flattened over the years 2017-19. Overall mortality rates between the 2013-2019 period for Black people with SCD were significantly lower compared to White people (62.1 vs 93.8 per 100,000, p&lt;0.001), but the difference was not significant in comparison to Black people without SCD (62.1 vs 69.4 per 100,000, p=0.33).
Opioid-related mortality in Black people with SCD has not significantly increased over time despite overall increased opioid-related mortality in Black people without SCD and White people. Further, Black people with SCD have significantly lower opioid-related mortality rates compared to White people. These data support continued efforts are needed to ensure access to opioid analgesics for individuals with SCD and promote SCD pain treatment as per evidence-based guidelines.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.