Higher hydroxyurea adherence among young adults with sickle cell disease compared to children and adolescents

Figures & data

Table 1. Participants’ characteristics.

	All (N = 113)	HbSS only (N = 99)
Age (years), median (IQR)	14 (10–20)	14 (10–28)
Age group (years), n (%)
Children (<12)	37 (32.7%)	29 (29.3%)
Adolescents (12–17)	26 (23%)	26 (26.3%)
Young adults (≥18)	50 (44.3%)	44 (44.4%)
Female, n (%)	57 (50.4%)	52 (52.53%)
Sickle cell genotype, n (%)
HbSS	99 (87.6%)	99 (100%)
HbSC	9 (8%)	–
Other^a	5 (4.4%)	–
HU indication, n (%)
Recurrent pain	35 (46.1%)	25 (38.5%)
CNS disease^b	11 (14.5%)	11 (16.92%)
Recurrent acute chest syndrome	5 (6.6%)	13 (20%)
≥1 of above indications	11 (14.5%)	11 (16.92%)
Others^c	12 (17.2%)	13 (20%)
HU dose (mg/kg/dose), median (IQR)	27.5 (23.3–30.8)	28 (24–32)
HU formulation, n (%)
Liquid	18 (16.2%)	17 (17.5%)
Tablet	93 (83.8%)	80 (82.5%)
HU MTD,^d n (%)	13 (11.6%)	13 (13.4%)
HU duration (months), median (IQR)	47 (20–60)	47 (20–60)
Chronic pain, n (%)	20 (17.7%)	17 (17.2%)
Cholecystectomy, n (%)	19 (16.8%)	17 (17.2%)
Splenectomy, n (%)	11 (9.7%)	9 (9.1%)
Insurance, n (%)
Private	64 (56.6%)	60 (60.6%)
Public/Medicaid	44 (38.9%)	34 (34.3%)
Combined^e	4 (3.5%)	4 (4%)
None	1 (0.9%)	1 (1%)
Distance to hospital (miles), median (IQR)	15.2 (9.5–30.9)	14.3 (9.5–30.6)
Laboratory markers (most recent), median (IQR)
Foetal haemoglobin (%)	14.5 (8.2–28.1)	15.3 (9.1–28.8)
Mean corpuscular volume (fl)	99.6 (90.4–112.5)	102.3 (92.6–112.9)
Absolute neutrophil count (10^3/ml)	3.8 (2.5–5.9)	3.8 (2.4–6)
SCD emergency room visits on HU (rate/year), median (IQR)	0.27 (0–2.0)	0.2 (0–1.6)
SCD hospitalizations on HU (rate/year), median (IQR)	0.33 (0–1.4)	0.24 (0–1.4)
SCD inpatient LOS on HU (days/year), median (IQR)	1 (0–20.6)	0.67 (0–5.2)

HU: hydroxyurea; LOS: length of stay; MTD: maximum tolerated dose; SCD: sickle cell disease.

^aOther genotype included HbSβ⁺ (n = 2), HbSβ⁰ (n = 2), HbS/Alpha-Thalassemia (n = 1).

^bCNS disease defined as stroke or abnormal transcranial Doppler.

^cOther hydroxyurea indications included poor growth (n = 5), anaemia (n = 3), transition from chronic transfusion (n = 3), hypoxia (n = 1), and abnormal imaging (n = 1). The remainder were not located in the EMR (n = 37).

^dMaximum tolerated dose was 35 mg/kg/d.

^eCombined insurance is referring to patients who had both public then private insurance over time, or vice versa.

Table 2. Laboratory markers of hydroxyurea adherence in relation to patients’ age and chronic pain status.

All participants (N = 113)
	Age groups (years)				Chronic pain
	<12 (n = 37)	12–17 (n = 26)	≥18 (n = 50)	p Value	Yes (n = 20)	No (n = 93)	p Value
HbF, median (IQR)
Most recent	8.6 (5.1–20.8)	12.4 (9.9–16.3)	24.2 (11.7–30.3)	.003	10.7 (4.6-19.5)	15.3 (8.9-29.3)	.04
Last year	8.4 (5.1–21.2)	14 (10.5–20.7)	24.4 (17.7–24.1)	.001	14.5 (4.9-20.7)	18 (9.8-29.4)	.24
Last 2 years	10.4 (5.1–15.5)	16.7 (12.4–24.4)	21.4 (15.2–26.4)	.01	17.4 (8.1-22.5)	16.1 (10.9-25)	.58
MCV, median (IQR)
Most recent	95.4 (81.6–102.4)	96.2 (90.9–113.1)	106.4 (92.6–116)	.01	93.1 (87.9–1003.5)	102.3 (91.4–112.7)	.1
Last year	96.4 (85.1–100.4)	94.6 (92.1–113.4)	106.2 (95.5–114.6)	.04	95.7 (89–112.1)	99.1 (92–113.4)	.46
Last 2 years	94.5 (85.7–101.1)	97.5 (92.3–112.5)	109.8 (97.3–113.7)	.01	96.6 (92.1–109.8)	100.8 (91.9–112.5)	.29
ANC, median (IQR)
Most recent	5 (2.9–5.9)	3.7 (2.7–6.1)	3.61 (2.3–5.7)	.5	6.3 (4–7)	3.6 (2.3–5.6)	.002
Last year	4.2 (3.4–6.8)	4.9 (3.6–6.6)	3.25 (2.4–4.7)	.01	4.2 (3.5–5)	3.77 (3–5.7)	.66
Last 2 years	4.4 (3.1–6.7)	4.8 (3.8–7)	3.9 (2.8–5.4)	.16	4.4 (3.9–6.2)	4.2 (3.1–6)	.6
Participants with HbSS (N = 99)
	Age groups (years)				Chronic pain
	<12 (n = 29)	12–17 (n = 26)	≥18 (n = 44)	p Value	Yes (n = 17)	No (n = 72)	p Value
HbF, median (IQR)
Most recent	9.25 (6.6–26.5)	12.4 (9.9–16.3)	24.3 (13.6–33.1)	.01	12.8 (8.7–22.6)	18.4 (9.1–30.3)	.12
Last year	9.55 (6.45–25.3)	14 (10.5–20.7)	24.4 (17.7–32.7)	.001	15.9 (9.0–22.8)	18.8 (10.5–29.4)	.29
Last 2 years	10.8 (5.3–21.6)	16.7 (12.4–24.4)	21.4 (15.2-26.4)	.03	17.8 (9.0–24.0)	16.8 (12.4–25)	.74
MCV, median (IQR)
Most recent	99.3 (92.5–104.9)	96.2 (90.9–113.1)	107.5 (93.6–116.1)	.08	96 (91.7–106.6)	104.1 (93.6–113.1)	.17
Last year	98.9 (94.9–104.5)	94.6 (92.1–113.4)	107 (95.8–114)	.18	95.9 (91.1–113.3)	100 (92.8–114)	.41
Last 2 years	96.7 (91.3–101.2)	97.5 (92.3–112.5)	110.9 (97.3–115.2)	.02	96.7 (92.5–110.4)	101.1 (94.8–113.7)	.28
ANC, median (IQR)
Most recent	5.1 (2.4–6.4)	3.7 (2.7–6.1)	3.5 (2.3–5.7)	.48	6.6 (6.9–3.5)	3.6 (2.3–5.6)	.003
Last year	4.2 (3.6–6.8)	4.9 (3.6–6.6)	3.2 (2.4–4.2)	.002	4.1 (3.2–5.9)	3.7 (3–5.5)	.65
Last 2 years	4.7 (4.1–7.7)	4.8 (3.8–7)	3.7 (2.7–5.2)	.04	4.3 (3.8–6.3)	4.2 (3.1–6.1)	.75

p <.05 was statistically significant (highlighted in bold).

ANC: absolute neutrophil count; HbF: foetal haemoglobin; IQR: inter-quartile range; MCV: mean corpuscular volume.

Table 3. Association between laboratory markers of hydroxyurea adherence and healthcare utilization.

All participants (N = 113)
	Emergency room visits (rate/year)				Hospitalizations (rate/year)				LOS hospitalizations (days/year)
	All (rs)	p Value	HU (rs)	p Value	All (rs)	p Value	HU (rs)	p Value	All (rs)	p Value	HU (rs)	p Value
HbF
Most recent	−0.18	.07	−0.26	.01	−0.21	.03	−0.27	.01	−0.23	.02	−0.27	.0045
Last 1 year	−0.27	.02	−0.30	.01	−0.25	.03	−0.30	.01	−0.26	.02	−0.32	.004
Last 2 year	−0.14	.36	−0.01	.32	−0.25	.04	−0.28	.02	−0.27	.03	−0.31	.01
MCV
Most recent	−0.20	.04	−0.23	.01	−0.18	.06	−0.14	.25	−0.22	.02	−0.14	.13
Last 1 year	−0.20	.08	−0.15	.17	−0.19	.08	−0.11	.32	−0.24	.03	−0.12	.27
Last 2 year	−0.24	.05	−0.18	.07	−0.31	.01	−0.17	.15	−0.34	.004	−0.19	.11
ANC
Most recent	0.23	.02	0.24	.01	0.22	.02	0.21	.02	0.22	.02	0.23	.02
Last 1 year	0.25	.02	0.25	.03	0.18	.11	0.17	.12	0.14	.20	0.15	.27
Last 2 year	0.14	.24	0.06	.66	0.18	.13	0.15	.22	0.16	.19	0.15	.23
Participants with HbSS (N = 99)
	Emergency room visits (rate/year)				Hospitalizations (rate/year)				LOS hospitalizations (days/year)
	All (rs)	p Value	HU (rs)	p Value	All (rs)	p Value	HU (rs)	p Value	All (rs)	p Value	HU (rs)	p Value
HbF
Most recent	−0.15	.14	−0.20	.045	−0.18	.09	−0.25	.015	−0.18	.08	−0.25	.01
Last 1 year	−0.21	.07	−0.21	.07	−0.17	.14	−0.22	.07	−0.17	.2	−0.23	.05
Last 2 year	−0.05	.56	−0.02	.87	−0.16	.22	−0.19	.15	−0.17	.2	−0.20	.11
MCV
Most recent	−0.16	.13	−0.14	.16	−0.16	.13	−0.11	.27	−0.22	.03	−0.12	.26
Last 1 year	−0.13	.25	−0.02	.88	−0.12	.29	−0.004	.97	−0.18	.11	−0.01	.93
Last 2 year	−0.24	.06	−0.08	.54	−0.27	.04	−0.15	.26	−0.31	.01	−0.16	.22
ANC
Most recent	0.21	.04	0.22	.03	0.26	.01	0.22	.03	0.27	.01	0.24	.02
Last 1 year	0.24	.04	0.23	.04	0.19	.11	0.16	.17	0.15	.18	0.16	.19
Last 2 year	0.16	.22	0.07	.60	0.24	.06	0.17	.19	0.22	.09	0.18	.16

p < 0.05 was statistically significant (highlighted in bold).

r_s, Spearman rho correlations; “All” is defined as entire follow up period, including HU therapy; “HU” is defined as being on HU.

ANC: absolute neutrophil count; HbF: foetal haemoglobin; HU: hydroxyurea; LOS: length of stay; MCV: mean corpuscular volume.

Table 4. Health care utilization in relation to patients’ age and chronic pain status, and duration of prescription.

All participants (N = 113)
	Age groups (years)				Chronic pain
	<12	12–17	≥18	p Value	Yes	No	p Value
Emergency room, median (IQR)
All	1.1 (0.3–2.2)	1.1 (0–2.0)	0.24 (0–2.0)	.32	1.9 (1.1–5.0)	0.6 (0–1.8)	<.001
On HU	1 (0-2.2)	0.40 (0-2.0)	0.20 (0-1.5)	.58	2.17 (1–4.25)	0 (0–1.4)	.001
Hospitalization, median (IQR)
All
Stays a year	0.6 (0–1.4)	0.74 (0.4–1.8)	0.4 (0–1.6)	.57	1.6 (0.5–4.2)	0.4 (0–1.2)	.001
Length of stay	2.0 (0–7.6)	3.95 (1.2–9.4)	1.8 (0–7.0)	.44	9.6 (3.2–24)	1.8 (0–7.0)	<.001
On HU
Stays a year	0 (0–1.4)	0.5 (0–1.6)	0.2 (0–1.4)	.45	1.8 (0.43–3.5)	0 (0–1.0)	<.001
Length of stay	0 (0–6.4)	1.7 (0–8.6)	0.64 (0–7.8)	.53	9.64 (2.87–3.3)	0 (0–3.0)	<.001
Participants with HbSS (N = 99)
	Age groups (years)				Chronic pain
	<12	12–17	≥18	p Value	Yes	No	p Value
Emergency room, median (IQR)
All	0.9 (0–2.0)	1.1 (0–2.0)	0.24 (0–2.0)	.56	2.0 (1.5–4.0)	0.4 (0–1.8)	<.001
On HU	0 (0–2.2)	0.40 (0–2.0)	0.20 (0–1.4)	.66	2.33 (1.4–4.0)	0 (0–1.0)	<.001
Hospitalization, median (IQR)
All
Stays a year	0.4 (0–1.2)	0.74 (0.4–1.8)	0.4 (0–1.6)	.37	2.0 (0.8–4.4)	0.4 (0–1.2)	<.001
Length of stay	1.8 (0–6.4)	3.95 (1.2–9.4)	1.6 (0–6.9)	.25	15 (3.4–25.6)	1.4 (0–5.2)	<.001
On HU
Stays a year	0 (0–1)	0.5 (0–1.6)	0.2 (0–1.4)	.26	2.0 (0.8–4.0)	0 (0–0.74)	<.001
Length of stay	0 (0–3.6)	1.7 (0–8.7)	0.67 (0–6.4)	.28	15 (3.4–25.6)	0 (0–2.44)	<.001

p <.05 was statistically significant (highlighted in bold).

HU: hydroxyurea; IQR: inter-quartile range.

“All” is defined as entire follow up period, including being HU therapy; “On HU” is defined as the period being on HU.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials. Data can be shared upon request by contacting the corresponding author.