Grndad and Disease Modifying Therapy (DMT): Shifts in Dmt Are Seen at the Adolescent/Young Adult Transition in Sickle Cell Disease in a Multi-Site Prospective Registry

The ability to characterize the modern person living with SCD in the US has been limited by the lack of a well-curated longitudinal registry. The Globin Research Network for Data and Discovery (GRNDaD) registry aims to overcome this challenge by collecting data from the now 53 IRB-approved centers across the US in collaboration with the National Alliance of Sickle Cell Centers (NASCC) and the HRSA-funded Sickle Cell Disease Treatment Demonstration Project Grant. Here, we describe the use of disease-modifying therapy in (actively consented) adults and children with Hgb SS/ SB⁰ thalassemia (SCA) from 37 sites.

Methods: Each site consents subjects and enters extensive baseline data including SCD complications and labs, subjects also complete patient-reported outcomes (PROs)-both at baseline and annually. Each subject is expected to have an annual follow-up where data is extracted from the Electronic Health Record (EHR). All data is stored in REDCap and, for this abstract, data were extracted into R on all active subjects (data entry in the last two years) who have complete minimum data collected. Median values were compared using Mann-Whitney U tests. Disease-modifying therapy (DMT) in this study comprises hydroxyurea (HU), chronic red blood cell (RBC) transfusions, crizanlizumab, L-glutamine, and voxelotor.

Results: There are 2501 active patients in GRNDaD. Twenty-six percent of subjects are pediatric </= 18 years of age, 55.5% are female and 66.7% have HgbSS or HgbSB⁰ thalassemia (SCA). Here, we report data on people with SCA only, whose minimum data were complete (n=1272). Table 1 shows DMT by age. 187 (21%) adults and 31 (8.5%) children were not on DMT. Figure 2 is a box plot of the absolute neutrophil count (ANC) comparing adults and children who are and are not taking HU. Adults on HU had significantly lower ANCs than those not on HU (median = 4.4 (IQR: 3.07, 6.3) v 6.6 (IQR:4.07, 8.14), p<0.001) (Figure). Similar findings were observed for children ( median = 3.5 (IQR:2.5, 5.7) Vs 8.1 (5.8, 12.8) , p =0.04) Both children and adults on HU had higher MCVs than those not on HU (median for peds: 91.5 (IQR: 85.1, 98.75) v 86 (IQR: 83.3, 86.1), p=0.05, median for adults: 96.5 (IQR: 89, 107) v 90 (IQR: 86.1, 95.1), p<0.001). We compared hemoglobin for those on and off HU, and on and off voxelotor, excluding patients on chronic transfusion therapy. There was a statistically significant difference in hemoglobin when comparing on or off of HU (median 8.9 g/dl (IQR 7.95, 9.9) v 8.2 g/dl (IQR: 7.2, 9.7, p =0.047)). There were no statistically significant differences in hemoglobin when comparing subjects on or off of voxelotor (median = 8.4 g/dl (IQR: 7.5, 9.6) vs 7.9 (IQR: 7.4, 9.8), p =0.57). In the adults, there were statistically significantly more males than females on HU, but there were no differences seen in the pediatric cohort. Examining DMT by age group, chronic RBC transfusion use doubled from the 11-17 age group to the 18–29-year age group (12% to 25%) and HU use decreased (83%-59%) over this same period.

Limitations: This cohort may over-represent those on DMT as those enrolled in GRNDaD were more likely to have clinic visits.

Discussion: GRNDaD has doubled the number of sites consenting subjects and entering data over the last year. The number is expected to increase again in the next 12 months, as an additional 15 sites are already IRB-approved with a goal to include all SCD centers in NASCC. This cross-sectional description of the current population of people living with SCD and treated in NASCC-recognized SCD centers in the US shows that the majority of those with SCA are receiving DMT. There is a noticeable decrease in HU use during the transition period with an increase in the use of chronic transfusion therapy. Newer DMT has had limited uptake in this cohort. The next steps will be to provide longitudinal data on this population and examine associations of DMT and important clinical outcomes including PROs.