The burden of immune thrombocytopenia in adults: Evaluation of the thrombopoietin receptor agonist romiplostim

Figures & data

Table 1.  Incidence of ITP from population-based studies.^a

Reference	Study location	Methodology	Inclusion criteria	Accrual years	Incidence per 100,000 adults/year	Age restrictions (years)
Frederiksen and Schmidt50	County of Funen, Denmark	Retrospective chart review	Patients identified using diagnosis codes from inpatient and outpatient records (ICD-8: 287.10, 287.11, 287.18, 287.19, and 675.09 or ICD-10: D69.3, D69.4, D69.5, D69.6 and O72.3) and included if they had a platelet count <100 × 10^9/L. Patients with solid tumors, other hematologic disorders, hepatic disease or alcoholism, lupus, TTP, drug- or gestation- induced TCP, DIC, or HIV were excluded. Relapsed cases were included if they had normal platelet counts for at least 2 years.	1973–1995	Total = 2.6*;2.3^† M = 2.0*;1.8^† F = 3.3*;2.7^†	≥16
				1985–1995	Total = 3.3*;2.7^† M = 2.4*;2.0^† F = 4.2*;3.3^†
Neylon et al.42	Northern Health Region, UK	Prospective cohort	Patients with a platelet count <50 × 10^9/L and bone marrow confirmation enrolled prospectively. Patients with gestational and therapy-related thrombocytopenia and all those with a proven cause for thrombocytopenia (drug-related) were excluded.	1993–1999	Total = 1.6^†	≥16
Abrahamson et al.47	UK	Retrospective secondary analysis	Patients identified using administrative codes in UK GPRD (42P2-11, D313--12, D313000, D312012, and 2871C). Patients included if they had 1 year of continuous enrollment in GPRD prior to ITP diagnosis code.	1992–2005	Total = 3.9, M = 3.2 F = 4.5	≥18
Schoonen et al.44	UK	Retrospective secondary analysis	Patients identified using administrative codes in UK GPRD (42P2-11, D312-11, D313-12, D313000, D312012, and 2871C).	1990–2005	Total = 3.8, M = 3.4 F = 4.4	All ages
				2000–2005	Total = 4.7, M = 4.4 F = 5.0
Kurata et al.41	Japan	Retrospective secondary analysis	Patients identified from nationwide register with a platelet count <100 × 10^9/L and bone marrow confirmation of ITP. Patients with a secondary immune disease that accounts for the thrombocytopenia were excluded.	2004–2007	Total = 2.2*, M = 1.7* F = 2.7*	≥14

^aOne study was not included in this table because it was not population-based: Franco-Garcia et al.49 reported an incidence rate of 1.15 per 100,000 persons in a hematology department in one hospital in Spain in 1994. The study by Bottiger and Westerholm48 was also not included in this table because the authors evaluated the incidence of thrombocytopenia, as opposed to ITP (8.1 and 4.2 per 100,000 females and males >14 years of age, respectively, per year in the Uppsala region of Sweden 1964–1968). Finally, Kurata et al.41 reported that an incidence rate of 2.3 per 100,000 (platelet count <100) was reported in a study by Takahashi et al. (2004), which is only available in Japanese, and is thus not included in this table.

*Platelet count <100 × 10⁹/L; ^†Platelet count <50 × 10⁹/L.

DIC, disseminated intravascular coagulation; GPRD, General Practice Research Database; HIV, human immunodeficiency virus; ITP, immune/idiopathic thrombocytopenia; IV, intravenous; TCP, thrombocytopenia; TTP, thrombotic thrombocytopenic purpura; M, males; F, females.

Table 2.  Prevalence rates of ITP from population-based studies.

Reference	Location	Methodology	Inclusion criteria	Accrual years	Prevalence rate per 100,000 adults/year	Age restrictions (years)
Landgren et al.54	US	Retrospective secondary analysis of VA database	African American and White males with ITP (ICD codes 287.1 and 287.3) identified from discharge records for inpatient hospitalizations at 142 nationwide VA hospitals.	7/1/1969–9/30/1996	African American M = 189.3* White M = 176.4*	≥18
Segal and Powe52	Maryland, US	Retrospective secondary analysis of private insurance database	Patients with at least two claims, separated by at least 30 or 180 days, for ICD-9 CM 287.3 were identified from a database of privately insured MD residents. Patients with concurrent diagnoses that made ITP unlikely (HIV, malignancy) were excluded.	2002	9.5* (codes separated by 30 days) 4.5*^ (codes separated by 180 days)	≥1 and ≤65
Feudjo-Tepie et al.53	US	Retrospective secondary analysis of managed care database	Patients enrolled in the health plan 2002–2006, with continuous enrollment in 2004 and at least two medical claims with ICD-9 codes 287.3 or 287.5 2000–2004 at least 6 months apart. Patients with HIV, hematological malignancies, or aplastic anemia were excluded.	2004	20.0*^	≥18
Saleh et al.10	US	Retrospective secondary analysis of healthcare database	At least two medical claims with ICD-9 codes for 287.3 or 287.5 2000–2004 at least 6 months apart, with the exclusion of persons with ITP codes indicating other platelet defects, non-thrombocytopenic purpuras, or secondary ITP.	2000–2004	0.08% or 80 per 100,000 persons^a^	≥18 on Jan. 1 2000

*Age-adjusted.

^Estimate of chronic ITP.

^aThe authors state “restricting the definition to chronic primary thrombocytopenia (i.e., ICD-9-CM code 287.3 only) reduced the prevalence estimate to 0.02%.” The reported prevalence estimate of 0.08% was obtained when using chronic idiopathic thrombocytopenia (i.e., ICD-9-CM code 287.3 and 287.5 [unspecified thrombocytopenia]).

HIV, human immunodeficiency virus; ICD, International Classification of Disease; ITP, immune/idiopathic thrombocytopenia; M, males; MD, Maryland VA, veteran’s administration.

Table 3.  Costs of illness studies for ITP.

Reference	Country (Currency)	Types of costs included (source)	Findings
Aledort et al.38	US (unknown $)	Inpatient, outpatient, laboratory, pharmacy (PharMetrics, 2000–2003)	Mean annual cost of care per patient was $23,420, 43% attributed to inpatient hospitalizations.
Danese et al.33	US (2008$)	Hospital costs (Nationwide Inpatient Sample, 2003–2006)	Mean cost per hospital discharge was $16,476 for ITP patients, compared to $10,039 for non-ITP patients; highest mean costs per discharge were associated with splenectomy ($21,754).
Khellaf et al.36	France (2005 €)	Hospital costs (French health care tariffs)	Mean annual costs were €7,293 for all patients, €15,334 for patients with at least one hospitalization, and €26,581 for patients with severe disease.
Lucioni et al.37	Italy (2008 €)	Inpatient, outpatient, laboratory, pharmacy (Italian healthcare tariffs)	Cost of illness to the NHS was estimated at €4 million per year, assuming 1200 adult patients.
Saleh et al.10	U.S. (unknown $)	Inpatient, outpatient, laboratory, pharmacy (HealthCore Integrated Research Network database, January 2000–February 2004)	Average ITP-attributable hospitalization cost per year was $4986; other ITP-attributable costs include $913 for diagnostic and treatment procedures, $367 for other outpatient visits, $299 for pharmacy, $260 for emergency department visits, $78 for office visits, and $27 for laboratory tests.
Tarantino et al.35	NA	Number of physician visits, work loss, work productivity (self-report)	Compared to controls, ITP patients were significantly more likely to have a primary care visit and a specialist care visit in the past month, more likely to have taken sick leave, and had difficulties with six productivity-related items. Visits, work loss, and productivity were not consistently related to years since diagnosis.

ITP, immune/idiopathic thrombocytopenic; NHS, National Health Service; NA, not available.

Table 4.  Costs associated with interventions in ITP.

Reference	Country (Currency)	Types of costs included (source)	Findings
Adams et al.95	US (2001 $)	Pharmacy (average wholesale price)	Annual cost of IVIg therapy in the US is $115–$693 million; assuming similar patient response, annual cost of anti-D is $49–$292 million if replacing IVIg; costs could be cut by 40% in RhD-positive patients.
Aledort et al.38	US (unknown $)	Inpatient, outpatient, laboratory, pharmacy (PharMetrics Integrated Medical and Pharmaceutical Database, 2000–2003)	Majority (82%) of patients had at least one claim for corticosteroid therapy during 12-month follow-up; 12% underwent splenectomy during follow-up; in splenectomized patients, 90% received corticosteroids and anti-D was administered more frequently than pre-splenectomy. Mean annual cost of care for splenectomized patients was $48,424; in non-splenectomized patients, costs were $20,110. Inpatient hospitalizations were the primary cost driver for splenectomized patients (39.6% of costs) and non-splenectomized patients (43.8% of costs).
Arocho et al.126	Mexico (2010 MXP$)	Cost of therapy and rescue medication over a 24-week period (Public Mexican Healthcare Perspective)	Cost per response^a was MXP$727,317 for romiplostim and infinite for placebo in splenectomized patients and MXP$456,912 for romiplostim and MXP$1,290,655 for placebo in non-splenectomized patients. Mean treatment costs in splenectomized patients were MXP$574,580 for romiplostim and MXP$301,218 for placebo and in non-splenectomized patients were MXP$402,083 for romiplostim and MXP$180,692 for placebo.
Brosa et al.97	Spain (2009 €)	Cost of therapy, rescue medication, and bleeding events over a 24-week period (national reimbursement rate)	Treatment costs over 24 weeks were €15,781 for all ITP patients treated with romiplostim, compared to €8,111 for placebo group (splenectomized patients €15,436 vs €10,263; non-splenectomized patients €16,125 vs €5958, respectively). Cost per response^b was €19,013 and €115,871, respectively, for romiplostim compared to placebo. ICER was not calculated.
Estrada-Gomèz et al.99	Spain (unknown US $)	Costs of treatment (20-year single institution study)	Costs of various treatments for a 60 kg adult, in US dollars, were $8,400–$30,000, $3,200 for anti-D, and $170 for anti-D opsonized autologous erythrocytes.
Lucioni et al.37	Italy (2008 €)	Inpatient, outpatient, laboratory, pharmacy (Italian health care tariffs)	Mean annual total medical costs for ITP were €3293 per patient. Of these, 56% were due to medications and 38% were due to hospitalizations. IVIg/anti-D treatments accounted for 97% of pharmacy costs.
Nelson et al.129	US (unknown $)	Hospitalizations and drug costs (Nationwide Inpatient Sample, 2003–2004)	Mean cost per splenectomy hospitalization was $16,557 (average LOS = 6.02 days); for hospitalizations without splenectomy, costs were $13,211 (LOS = 5.55 days).
Northridge et al.124	US (2010 $)	Medicare-covered costs of treatment, administration, on-going patient management, adverse events, and bleeding-related events (Medicare Fee Schedule)	Model estimates the 6-month cost per patient with durable response in splenectomized patients were $110,589 and $325,320 for those treated with romiplostim compared to watch-and-rescue, respectively; in non-splenectomized patients, 6-month costs per durable response were $58,598 and $89,486, respectively.
Ruggeri et al.34	Italy (2005 €)	Hospital costs (Italian Health Service, 1997–2007)	Total cost was €10,780 per patient; major expenses were associated with splenectomy interventions and recurrent admissions for high-cost rescue therapies.
Vainchtock et al.106	France (2007 €)	Hospital costs (French healthcare tariffs)	Mean charge per ITP-related hospitalization were €3,653 for public hospitals, €3,177 for private hospitals, and €6,367 for ITP-related splenectomy. Patients had an average of 2.8 (public hospital) to 3.4 (private hospital) stays per year.
Xie et al.100	Canada (2007 $CAD)	Modeled lifetime medical costs	Incremental cost-effectiveness of IVIg compared to prednisone was $1.13 million per QALY.

^a≥4 weekly platelet responses ≥50 × 10⁹/L from Weeks 2 to 25.

^bPlatelet response ≥50 × 10⁹/L.

CAD, Canadian dollars; ICER, incremental cost-effectiveness ratio; ITP, immune thrombocytopenic; IV, intravenous; IVIg, intravenous immunoglobulin; LOS, length of stay; MXP, Mexican peso; QALY, quality-adjusted life-year.

Table 5.  Treatments and costs for ITP therapies*.

Reference	Country (currency)	Treatment	Reported costs (dosage)
Adams et al.95	US (2001 $)	Anti-D	$3,780 (low dose)–$5,680 (high dose) (50 µg/kg × 1 day–75 µg/kg × 1 day) With infusion: $3,824 (low dose)–$5,724 (high dose)
Adams et al.95	US (2001 $)	IVIg	$4,850 (low dose)–$13,300 (high dose) (0.8 g/kg × 1 day–1.0 g/kg × 2 days) With infusion: $4,986 (low dose)–$13,436 (high dose)
Blackhouse et al.96	Canada (2007 $)	IVIg	$550–$1,000 per infusion (0.5–1.0 g/kg for 20 kg child) ,$4,000 per infusion (1 g/kg for 70 kg adult)
Brosa et al.97	Spain (2009 €)	IVIg	Unit cost €5,376
Chiche et al.110	France (unknown $)	IVIg	€6,462 per dose (1 g/kg × 2 days)
Pettigrew et al.125	Canada (unknown $)	IVIg	Annual cost per patient was $107,041 (1 g/kg × 4 weeks, average administration of 3.5 hours)
Ruggeri et al.34	Italy (2005 €)	IVIg	Total cost per patient €1639
Xie et al.100	Canada (2007 $CAD)	IVIg	$59.19 per gram (range, $51–64)
Adams et al.95	U.S. (2001 $)	Prednisone	$25 per course (4 mg/kg taper × 17 days)
Blackhouse et al.96	Canada (2007$)	Prednisone	Dose: $0.09 per 50 mg tablet Course: $0.73 per 20 kg child
Chiche et al.110	France (unknown $)	Prednisone	€6 per dose (€0.045/mg unit dose) (2 mg/kg daily × 2 weeks)
Xie et al.100	Canada (2007 $CAD)	Prednisone	$0.09 per 50 mg tablet
Chiche et al.110	France (unknown $)	Rituximab	€2,647 per dose (375 mg/m^2, 4 weekly infusions)
Chiche et al.110	France (unknown $)	Romiplostim	€688 per dose (2.5 mcg/kg once weekly)
Pettigrew et al.125	Canada (unknown $)	Romiplostim	Average annual cost of $50,950 based on 3 mcg/kg weekly
Perreault and Burzynski28	US (2008 $)	Romiplostim	Average whole price of 250 mcg vial is $1,062.50 and $2,125.00 for 50 mcg vial. Annual drug cost per patient is ∼ $55,250.
Adams et al.95	US (2001 $)	Splenectomy	$16,000**
Blackhouse et al.96	Canada (2007 $CAD)	Splenectomy	Mean = $11,709 (95% CI: $3,251–$85,452)
Xie et al.100	Canada (2007 $CAD)	Splenectomy	$11,709 (range, $3,251–$85,452)

CAD, Canadian dollars; CI, confidence interval; IVIg, intravenous immunoglobulin.

*Studies reporting costs solely based on national health tariffs were not included in this table. Some studies relied on national health tariffs (e.g., Chiche et al.110), but included additional administration and other costs to determine total costs; these studies were included for comparative purposes.

**Based on literature reviews.

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