P1482: PATIENTS WITH SEVERE SICKLE CELL DISEASE ON STANDARD OF CARE TREATMENT ARE VERY UNLIKELY TO BECOME VOC FREE FOR ONE YEAR: A COHORT STUDY OF MEDICAID ENROLLEES

Abstract

Background: Sickle cell disease (SCD) patients have frequent vaso-occlusive crises (VOCs), which impact their quality of life, contribute to organ damage and failure, and are associated with increased mortality. An ongoing, open-label Ph3 clinical trial with CTX001, an investigational, autologous, ex vivo CRISPR/Cas-9-based gene edited therapy, in patients with severe SCD, is evaluating the proportion of patients who become VOC-free for at least 1 year after CTX001 treatment. Thus, it is important to know the proportion of patients with severe SCD on standard-of-care (SOC) who become VOC-free over time to provide context for the efficacy of CTX001 in eliminating VOCs in severe SCD. Aims: To contextualize the efficacy of CTX001 in eliminating VOCs in patients with severe SCD, we used nationwide Medicaid claims data from 2000 to 2014 to assess the proportion of patients on SOC who became VOC-free during a 1-year follow-up. The inclusion/exclusion criteria were similar to those of the Ph3 clinical trial of CTX001 in patients with severe SCD. Methods: A cohort of patients 12-35 years old with SCD was identified based on ≥1 inpatient claim or ≥2 outpatient claims for SCD after at least 2 years of continuous Medicaid enrollment. The date patients met the SCD case algorithm was defined as the cohort entry date. The 2-year period preceding the cohort entry date was defined as the baseline period. Consistent with the inclusion criteria in the CTX001 Ph3 trial, we restricted this population to severe SCD defined by ≥2 VOCs per year in each of 2 consecutive years (total of ≥4 VOCs over 2 years) at baseline. A VOC was identified using ICD diagnosis codes in hospitalization and ER visit claims for acute pain crisis, acute chest syndrome, priapism, and splenic sequestration. Additional exclusion criteria that were operationalizable using claims data included prior bone marrow transplant, moyamoya syndrome or history of stroke, low left heart function, low lung diffusing capacity (including pulmonary hypertension), advanced liver disease, decreased kidney function, significant bleeding disorder, prior malignancy or myelodysplasia, and select infections. We further restricted the cohort to patients with 1-year of continuous Medicaid enrollment (or less if any deaths) following the cohort entry. The primary outcome was the proportion of patients with 0 VOCs during a 1-year follow-up. Results: A total of 5,874 patients with severe SCD were identified [mean (SD) age: 20.5 (6.0) years, 54.4% female, 87% African Americans]. Patients had a mean of 5.1 VOCs, 4.7 ER visits and 3.6 all-cause hospitalizations per year during the 2-year baseline period. Hydroxyurea was used in 37.5%, opioid analgesics in 88.7%, and NSAIDs in 71.9%. The proportion of patients with 0 VOCs during the 1-year follow-up was 9.1% (95% CI: 8.4, 9.9). When stratified by the number of VOCs at baseline, patients with higher numbers of VOCs had a lower proportion of 0 VOCs in the 1-year follow-up (Table). Image:Summary/Conclusion: Fewer than 10% of patients with severe SCD with at least 2 VOCs per year in the prior 2 years at baseline became VOC-free for 1 year with SOC in this nationwide cohort of Medicaid enrollees. This demonstrates that patients with severe SCD are very unlikely to become VOC-free over a 1-year period and provides context for the efficacy of gene therapies in eliminating VOCs. These data also highlight the urgent need to develop effective therapies for patients with severe SCD as ~90% of patients continue to have VOCs, which are life-limiting and life-threatening events.