Trends and in-Hospital Mortality of Acute Chest Syndrome in Sickle Cell Disease: Did Crinzalizumab Make a Difference? - an NIS Database Study 2015-2020
Authors: Vijay Rao Aniket , Sanjeevi Aditya , Jose Domench Daniel Idoate , Bhandari Samikchhya Keshary , Kharel Himal 
Published: December 2024

Objective: Our study seeks to identify trends in acute chest syndrome hospitalizations and outcomes for adult patients with sickle cell disease from 2015 to 2020. This investigation emphasizes how these changed after 2019 with the introduction of Crinzalizumab (FDA approved in November 2019) given its presumed huge impact on the incidence and outcome of vaso-occlusive crises. We further investigate the trends in healthcare utilization, mortality rate, demographic data of the patients and institutional characteristics.

Methods: We used the National Inpatient Sample (NIS) databases from 2015-2020 provided by the Healthcare Cost and Utilization Project, HCUP to conduct a retrospective analysis. International Classification of Diseases (ICD) codes were used to code for acute chest syndrome in patients with sickle cell diseases. This study did not require Institutional review board IRB) approval as the NIS consists of de-identified data. We used the discharge weight available in the database (DISCWT) to derive the national estimates. We could not perform multivariate logistic regression analysis to estimate the odds of mortality given the low numbers of mortality in the study period.

Results: Their median age was 20 years (IQR: 9-32 years), and 47.27% were females. Besides, 88.69% of patients were Blacks. Most hospitalizations, 57.31%, were in large urban teaching hospitals. Geographically, most of the hospitalizations were in the South, at 47.81%. Among the different types of sickle cell crises, Hb-SS disease with crisis represented the largest percentage share of about 47.71% with 4420 cases, followed by sickle cell disease with crisis and other sickle cell diseases at 34.54% with 3200, sickle cell thalassemia with crisis at 17.0% with 1595, and sickle cell/HB-C disease with crisis at 1.78% with 165. Distinctly, the trends of the analysis show that ACS hospitalizations and outcomes differ across the years. Back in 2015, there were 785 ACS hospitalizations, increasing the next year to 1700 in 2016, 1780 in 2017, and 1675 in 2018. The highest point reached was in 2019, which had 1805 hospitalizations. The cases declined to 1520 in 2020. This happened in the year when, after being FDA-approved in November 2019, Crinzalizumab was introduced. 3.82% of ACS patients needed an exchange transfusion in 2015. This number declined in the ensuing years until 2018, and then rose in 2019 to 2.49%, reaching a peak of 4.93% in 2020. There has been a slight increase in PLEX use from 0% in 2015 to 0.88% in 2016, 1.12% in 2017, 0.60% in 2018, 0.28% in 2019, and 1.64% in 2020. The need for mechanical ventilation has been increasing progressively from 1.91% in the year 2015 to 3.82% in 2016, 3.37% in 2017, 3.28% in 2018, and 4.16% in 2019. In 2020, the use of mechanical ventilation drastically increased to 6.25%. This could, in part, be related to the COVID-19 pandemic, which had perhaps exacerbated the severity of ACS and further increased the demand for mechanical ventilation. In summation, the total patients on mechanical ventilation &gt; 96 hours was 165 (1.78 %), while those requiring mechanical ventilation &lt; 96 hours were 150 (1.62%). Another study demonstrated worse mortality rates for patients with ACS during the pandemic and therefore speculated that COVID-19 added to the severity of ACS and worsened the outcome. Mortality rates also showed an alarming increasing trend, from 0.64 percent in 2015, 0.59 percent in 2016, 0.56 percent in 2017, 0.90 percent in 2018, and 0.83 percent in 2019. Whereas in 2020, the mortality rate increased to 2.30% which could be due to the impact COVID-19 had on patients' health status and the strain it placed on health resources.

Conclusion: The study demonstrates a concerning increasing trend in the requirement for mechanical ventilation and an increasing mortality rate among ACS hospitalizations in adult sickle cell patients from 2015 to 2020. The abrupt rise in 2020 could be partly due to the COVID-19 pandemic. The FDA's approval of Crinzalizumab in 2019, shown to reduce the incidence of vaso-occlusive crises, may underline the drop in ACS hospitalizations seen in 2020. We could not assess for predictors of mortality due to low numbers in terms of mortality. It will be very important to further investigate the trends of ACS with Crinzalizumab to underpin its role in improving patient outcomes.