Real-World Experience of Patients with Sickle Cell Disease Treated with Crizanlizumab: A Single Comprehensive Sickle Cell Center Retrospective Cohort Analysis

Background:Sickle cell disease (SCD) is an inheritable hemoglobinopathy with great impact on patients’ quality of life and healthcare costs. In 2019, crizanlizumab, the first-in-class monoclonal antibody that target the cell adhesion molecule P-selectin, was approved by the FDA to reduce the rate of vaso-occlusive crisis in patients with SCD ≥16 years old, based on the results of the SUSTAIN trial [1].

Aim: To study the real-world effectiveness of crizanlizumab in patients with SCD ≥16 years old treated with crizanlizumab 5.0 mg/kg, with or without hydroxyurea, from 2019 to 2022 in our comprehensive sickle cell center.

Methods: This is a retrospective cohort analysis of patients with SCD (all genotyped, ≥16 years old) who received at least 2 consecutive doses of crizanlizumab. Demographics and laboratory findings before and after crizanlizumab were collected and analyzed. Only data available from patients’ electronic medical records (and other secondary data sources) 1 year before (pre-index data) and after (post-index data) the ≥2 consecutive crizanlizumab doses were analyzed. Objective clinical improvement was captured using the Patients’ Global Impression of Change (PGIC) score. Descriptive statistics are presented in percentages, medians, and interquartile ranges. An independent group unpaired Student's t-test was used to determine, where appropriate, the level of significant differences among normal distribution continuous variable with p value <0.05 considered statistically significant. Data was analyzed using GraphPad Prism version 9.0.2.

Results:As of July 2022, there were 18 patients eligible for analysis. The median age of patients was 30.5 (range, 19-47) years, 7 (38%) males and 11 (61%) females (Table 1). Eight patients had the HbSS genotype, 7 HbSC, and 3 HbSB null. The median duration of exposure to crizanlizumab was 53.6 weeks, and 16 (89%) patients received crizanlizumab for ≥26 weeks. Crizanlizumab is very well tolerated with no serious adverse events (grade ≥3) related to treatment reported. The most commonly reported adverse events were fatigue (n=3), followed by headache (n=2) and nausea (n=2).

There was no significant difference in laboratory parameters (hemoglobin, hematocrit, total bilirubin, creatinine, or protein/creatinine ratio) between pre-index and post-index values (Table 2). Although there was improvement in reticulocytes (6.5% vs. 5.1%) and LDH (336.5 vs. 279 U/L) compared with baseline, this was not statistically significant, likely due to the small sample size (p=0.71 and p=0.98, respectively).

There was a remarkable improvement in patients’ subjective response with crizanlizumab infusion. The median PGIC score of our patients was 5, signifying moderately better with noticeable changes, although slight. Twelve (67%) patients provided a score of ≥4, which signifies feeling better with changes.

Conclusions: This is one of the first retrospective studies to use PGIC to capture the effectiveness of crizanlizumab in patients with SCD. This study shows that crizanlizumab was associated with an improvement in patient response that was directly and indirectly related to the reduction of vaso-occlusive crisis, consistent with findings from the SUSTAIN trial. Further large-scale studies are needed to corroborate these findings.

References: 1. Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017;376(5):429-439.

Idowu:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Forma: Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Ironwood: Research Funding.