Background: Sickle Cell Anemia (SCA) is the most common form of Sickle Cell Disease (SCD), defined by lifelong hemolytic anemia, pain crises, and end-organ damage. CDC estimates that 1 in 365 African-Americans are affected with SCD, and 1 in 13 babies born to African-American parents have Sickle cell trait (SCT). Vaso-occlusive crisis (VOC), the most frequent complication in adults, leads to hospitalizations, missed school/work, and poor quality of life. A large 2025 retrospective analysis found SCA patients average 5.84 VOCs/year, highlighting the need to prevent VOCs as a key treatment target. This study compares the effectiveness of Crizanlizumab in reducing VOCs and hospitalizations.

Methods: This is a retrospective cohort analysis using the TriNetX database, a global health research network that provides data from electronic medical records from large healthcare organizations. Patients aged 18 years or older with HbSS SCD who had experienced at least one vaso-occlusive crisis (VOC) in the year preceding treatment with crizanlizumab were included in the study. Patients were stratified into 2 cohorts based on the use of crizanlizumab. A propensity score matching analysis (1:1) was performed to adjust for potential confounders, including age, gender, HbS level, HbF level, and use of hydroxyurea. The primary outcome was determined to compare the rate of VOCs in patients on crizanlizumab with those who are not on Crizanlizumab at 3, 6, 12, and 36-month intervals. The Secondary outcome was derived as the number of hospitalizations. Results were obtained through measure of association analysis, including relative risk, confidence intervals, and p-values.

Results: This study included 2,036 patients, who were divided equally into two groups: 1,018 received crizanlizumab (mean age, 30.3 years; 61% female; mean HbS, 58.7%; mean HbF, 9.0%), and 1,018 did not (mean age, 30.3 years; 61.1% female; mean HbS, 63.3%; mean HbF, 10.6%). In both groups, 66.9% (682) were on hydroxyurea. Patients receiving crizanlizumab had higher Relative Risk (RR) of VOCs at each time point: 3 months (1.675, 95% CI 1.549-1.811, p<0.001), 6 months (1.498, 1.406-1.597, p<0.001), 12 months (1.418, 1.345-1.494, p<0.001), and 36 months (1.320, 1.266-1.375, p<0.001). Hospitalization risk was similarly elevated with crizanlizumab: 3 months (2.322, 1.736-3.106, p<0.001), 6 months (1.514, 1.308-1.752, p<0.001), 1 year (1.575, 1.403-1.768, p<0.001), and 3 years (1.444, 1.311-1.591, p<0.001).

Conclusion: This study showed that crizanlizumab alone or with Hydroxyurea was associated with higher rates of VOCs and hospitalization than those not on Crizanlizumab, indicating inferior outcomes and supporting the need for further research into novel therapeutics for SCD.

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2025
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