Heterogeneity of the long-term economic burden of severe sickle cell disease: a 5-year longitudinal analysis

Figures & data

Table 1. Sample attrition.

	Commercial/Medicare		Medicaid		All patients
Patients with ≥2 claims (within 1 year) for sickle cell disease (SCD) between 01/01/2010 and 12/30/2018 (first claim serves as index date)	23,943	100.0%	24,760	100.0%	48,703	100.0%
Continuous enrollment for ≥60 months following index	2,305	9.6%	7,915	32.0%	10,220	21.0%
No evidence of claims for a stem cell transplant (SCT) during follow-up	2,256	9.4%	7,820	31.6%	10,076	20.7%
No evidence of dual enrollment in Medicare/Medicaid during follow-up	2,256	9.4%	6,108	24.7%	8,364	17.2%
Patients meeting any one of the acute VOEs or history of stroke^a and/or  other disease-related sequelae^b in the 24 months following index	934	3.9%	3,553	14.4%	4,487	9.2%

^a≥4 hospitalizations or ER visits with vaso-occlusive crisis or pain crises, splenic sequestration, hepatic sequestration, or priapism OR ≥1 medical claim with ACS, ischemic or hemorrhagic stroke or history of stroke.

^b≥1 medical claim with osteomyelitis (subacute, acute, or chronic), septicemia or sepsis, splenic infarction, acute kidney injury or any stage of chronic kidney disease (CKD), acute renal failure, venous thromboembolism, deep vein thrombosis, pulmonary embolism, osteonecrosis, pulmonary hypertension, pre-eclampsia or eclampsia, hepatic sequestration/infarction (also included in the acute list), ischemic or hemorrhagic stroke or history of stroke (also included in the acute list), or non-pressure ulcers.

Table 2. Demographic, clinical, and treatment characteristics.

	Commercial/Medicare		Medicaid
	N =	934	N =	3,553
Age (mean, SD)	28.3	19.2	15.2	14.3
Age (N,%)
<18	349	37.4%	2,258	63.6%
18–30	167	17.9%	765	21.5%
≥31	418	44.8%	530	14.9%
Sex (N, %)
Male	379	40.6%	1,685	47.4%
Female	555	59.4%	1,868	52.6%
Race (N, %)
White			41	1.2%
Black			2,651	74.6%
Hispanic			26	0.7%
Other/Unknown			835	23.5%
Geographic region (N, %)
Northeast	203	21.7%
North Central	163	17.5%
South	511	54.7%
West	51	5.5%
Unknown	6	0.6%
Comorbidities and disease-related complications (N, %)
Hematological
Anemia	709	75.9%	2,711	76.3%
Iron disorders (disorder of iron metabolism)	152	16.3%	732	20.6%
Splenic sequestration	45	4.8%	451	12.7%
Venous thromboembolism^a	98	10.5%	359	10.1%
Infarction of spleen	47	5.0%	345	9.7%
Hyposplenism	44	4.7%	344	9.7%
Cardiopulmonary
Acute chest syndrome	317	33.9%	1,784	50.2%
Cardiomegaly	185	19.8%	895	25.2%
Obstructive sleep apnea	104	11.1%	614	17.3%
Pulmonary hypertension	117	12.5%	413	11.6%
Genitourinary
Priapism	25	2.7%	208	5.9%
Erectile dysfunction	32	3.4%	49	1.4%
Cerebrovascular
Cerebrovascular symptoms^b	168	18.0%	845	23.8%
Stroke, history	137	14.7%	592	16.7%
Stroke, ischemic	117	12.5%	469	13.2%
Neurocognitive impairment	64	6.9%	296	8.3%
Transient ischemic attack	46	4.9%	163	4.6%
Neurocognitive impairment (without stroke)	30	3.2%	155	4.4%
Stroke, hemorrhagic	27	2.9%	60	1.7%
Hepato-renal
Indirect hyperbilirubinaemia^c	173	18.5%	660	18.6%
Acute renal failure	144	15.4%	372	10.5%
Acute kidney injury	139	14.9%	361	10.2%
Chronic kidney disease	141	15.1%	237	6.7%
Hepatic sequestration	1	0.1%	4	0.1%
Bone and musculoskeletal
Chronic pain	765	81.9%	2,863	80.6%
Osteonecrosis/avascular necrosis	255	27.3%	748	21.1%
Osteomyelitis	51	5.5%	163	4.6%
Other
Depression and anxiety	221	23.7%	1,322	37.2%
Sepsis or Septicemia	205	21.9%	760	21.4%
Non-pressure ulcers	62	6.6%	115	3.2%
Pre-eclampsia or eclampsia	7	0.7%	69	1.9%
Treatments (N, %)
Antibiotics	881	94.3%	3,478	97.9%
Oral opioids	855	91.5%	3,354	94.4%
NSAIDs	676	72.4%	3,149	88.6%
Hydration therapy	482	51.6%	2,657	74.8%
Intravenous opioids	447	47.9%	2,282	64.2%
Hydroxyurea	413	44.2%	1,947	54.8%
Blood transfusions	290	31.0%	1,225	34.5%
Iron Chelation	126	13.5%	558	15.7%
Other opioids	75	8.0%	429	12.1%

Demographics were measured on the index date. Clinical and treatment characteristics were assessed over the 5-year follow-up.

^aIncludes deep vein thrombosis and pulmonary embolism.

^bIncludes development disorder, amnesia, transient ischemic attack, occlusion of carotid artery or cerebral artery, occlusion with no mention of infarction, cerebral artery syndrome, hemiplegia, and cerebral ischemia.

^cInclude retinopathyolelithiasis, choledocholithiasis, cholangiopathy, viral hepatitis, and sickle cell cholangiopathy.

Figure 1. Mean vaso-occlusive events (VOEs) over the 5-year follow-up.

Table 3. Comorbidities and disease-related complications over the 5-year follow-up by age groups.

	Commercial and Medicare						Medicaid
	<18		18–30		≥31		<18		18–30		≥31
	N =	349	N =	167	N =	418	N =	2,258	N =	765	N =	530
Hematological
Anemia	206	59.0%	142	85.0%	361	86.4%	1513	67.0%	715	93.5%	483	91.1%
Venous thromboembolism^a	14	4.0%	20	12.0%	64	15.3%	46	2.0%	179	23.4%	134	25.3%
Iron disorders (disorder of iron metabolism)	44	12.6%	41	24.6%	67	16.0%	366	16.2%	258	33.7%	108	20.4%
Infarction of spleen	17	4.9%	13	7.8%	17	4.1%	303	13.4%	25	3.3%	17	3.2%
Splenic sequestration	35	10.0%	5	3.0%	5	1.2%	406	18.0%	29	3.8%	16	3.0%
Hyposplenism	18	5.2%	11	6.6%	15	3.6%	303	13.4%	26	3.4%	15	2.8%
Cardiopulmonary
Cardiomegaly	62	17.8%	34	20.4%	89	21.3%	456	20.2%	267	34.9%	172	32.5%
Pulmonary hypertension	21	6.0%	24	14.4%	72	17.2%	96	4.3%	181	23.7%	136	25.7%
Acute chest syndrome	173	49.6%	64	38.3%	80	19.1%	1300	57.6%	363	47.5%	121	22.8%
Obstructive sleep apnea	54	15.5%	12	7.2%	38	9.1%	441	19.5%	76	9.9%	97	18.3%
Genitourinary
Erectile dysfunction	0	0.0%	4	2.4%	28	6.7%	5	0.2%	21	2.7%	23	4.3%
Priapism	10	2.9%	8	4.8%	7	1.7%	130	5.8%	63	8.2%	15	2.8%
Cerebrovascular
Cerebrovascular symptoms^b	64	18.3%	12	7.2%	92	22.0%	559	24.8%	161	21.0%	125	23.6%
Stroke, history	50	14.3%	26	15.6%	61	14.6%	312	13.8%	174	22.7%	106	20.0%
Stroke, ischemic	44	12.6%	11	6.6%	62	14.8%	255	11.3%	117	15.3%	97	18.3%
Neurocognitive impairment	23	6.6%	8	4.8%	33	7.9%	165	7.3%	69	9.0%	62	11.7%
Transient ischemic attack	7	2.0%	0	0.0%	39	9.3%	83	3.7%	32	4.2%	48	9.1%
Neurocognitive impairment (without stroke)	9	2.6%	6	3.6%	15	3.6%	82	3.6%	38	5.0%	35	6.6%
Stroke, hemorrhagic	10	2.9%	1	0.6%	16	3.8%	36	1.6%	17	2.2%	7	1.3%
Hepato-renal
Acute renal failure	14	4.0%	19	11.4%	111	26.6%	51	2.3%	142	18.6%	179	33.8%
Acute kidney injury	11	3.2%	19	11.4%	109	26.1%	46	2.0%	139	18.2%	176	33.2%
Chronic kidney disease	9	2.6%	15	9.0%	117	28.0%	40	1.8%	71	9.3%	126	23.8%
Indirect hyperbilirubinaemia^c	67	19.2%	31	18.6%	75	17.9%	377	16.7%	162	21.2%	121	22.8%
Hepatic sequestration	0	0.0%	1	0.6%	0	0.0%	1	0.0%	1	0.1%	2	0.4%
Bone and musculoskeletal
Chronic pain	236	67.6%	153	91.6%	376	90.0%	1629	72.1%	723	94.5%	511	96.4%
Osteonecrosis/avascular necrosis	53	15.2%	53	31.7%	149	35.6%	279	12.4%	285	37.3%	184	34.7%
Osteomyelitis	19	5.4%	6	3.6%	26	6.2%	92	4.1%	36	4.7%	35	6.6%
Other
Depression and anxiety	42	12.0%	50	29.9%	129	30.9%	545	24.1%	446	58.3%	331	62.5%
Sepsis or Septicemia	42	12.0%	50	29.9%	113	27.0%	256	11.3%	312	40.8%	192	36.2%
Non pressure ulcers	1	0.3%	10	6.0%	51	12.2%	9	0.4%	47	6.1%	59	11.1%
Pre-eclampsia or eclampsia	2	0.6%	3	1.8%	2	0.5%	12	0.5%	50	6.5%	7	1.3%

^aIncludes deep vein thrombosis and pulmonary embolism.

^bIncludes development disorder, amnesia, transient ischemic attack, occlusion of carotid artery or cerebral artery, occlusion with no mention of infarction, cerebral artery syndrome, hemiplegia, and cerebral ischemia.

^cIncludes retinopathyolelithiasis, choledocholithiasis, cholangiopathy, viral hepatitis, and sickle cell cholangiopathy.

Table 4. Treatment utilization over the 5-year follow-up by age group.

	Commercial and Medicare						Medicaid
	<18		18–30		≥31		<18		18–30		≥31
	N =	349	N =	167	N =	418	N =	2,258	N =	765	N =	530
Treatments (N, %)
Oral opioids	316	90.5%	156	93.4%	383	91.6%	2,089	92.5%	751	98.2%	514	97.0%
Antibiotics	333	95.4%	160	95.8%	388	92.8%	2,235	99.0%	736	96.2%	507	95.7%
NSAIDs	236	67.6%	136	81.4%	304	72.7%	1,979	87.6%	708	92.5%	462	87.2%
Intravenous opioids	140	40.1%	96	57.5%	211	50.5%	1,191	52.7%	671	87.7%	420	79.2%
Hydration therapy	173	49.6%	110	65.9%	199	47.6%	1,640	72.6%	649	84.8%	368	69.4%
Hydroxyurea	175	50.1%	92	55.1%	146	34.9%	1,205	53.4%	521	68.1%	221	41.7%
Blood transfusions	105	30.1%	66	39.5%	119	28.5%	701	31.0%	355	46.4%	169	31.9%
Other opioids	13	3.7%	20	12.0%	42	10.0%	152	6.7%	168	22.0%	109	20.6%
Iron chelation	42	12.0%	30	18.0%	54	12.9%	313	13.9%	168	22.0%	77	14.5%

Figure 2. Mean all-cause total healthcare costs over the 5-year follow-up.