Healthcare resource use and direct costs in severe aplastic anemia (SAA) patients before and after treatment with eltrombopag

Abstract

Purpose: This study evaluated healthcare resource utilization (HCRU), and direct costs among severe aplastic anemia (SAA) patients treated with eltrombopag (EPAG) using US claims data.

Methods: This retrospective, real-world claims database study identified SAA patients aged ≥2 years treated with EPAG who initiated any SAA treatment between 1 July 2014 and 31 December 2017 (identification period) using the Truven MarketScan databases. A subset of 82 patients treated with EPAG during the identification period were evaluated for all-cause and SAA-related HCRU and direct costs as well as blood transfusion 1 month before EPAG initiation (baseline) and at Month 6 after EPAG initiation (follow-up period).

Results: The average patient age was 50.8 (SD = 20.6) years old, predominantly female (n = 43, 52.4%), and had a mean CCI at baseline of 1.1 (SD = 1.7). Hospitalizations, and ER, office, and outpatient visits were significantly lower at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (p < .05 for all four all-cause HCRU and SAA-related hospitalizations). An almost two-fold decrease in reliance on biweekly blood transfusions was observed: 1.0 at weeks 1–2 to 0.5 at Month 6 after EPAG initiation. Although prescription costs (mean [SD]) were significantly higher at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (difference of $11,045 USD [SD = $18,801]), these increases were offset by savings in direct costs. Overall, a mean reduction in total all-cause costs of $29,391 USD [SD = $137,770] was reported at Month 6 after EPAG initiation due to substantial reductions in hospitalization ($40,060 USD [SD = $123,198]) and outpatient visits ($2,043 USD [SD = $25,264]).

Conclusion: All-cause and SAA-related HCRU were reduced following EPAG treatment. Prescription costs were higher following treatment; however, these costs were generally offset by reductions in direct costs. These results provide real-world evidence around the role of EPAG in SAA treatment.

Keywords:

• Severe aplastic anemia
• eltrombopag
• blood transfusion
• healthcare resource utilization
• direct costs
• immunosuppressive therapy

JEL CLASSIFICATION CODES:

• I10
• I19

This article is related to:

Healthcare costs and resource utilization in patients with severe aplastic anemia in the US

Introduction

Severe aplastic anemia (SAA) is a disorder in which the bone marrow stops producing enough blood cells to maintain a person’s health^1,2. Patients with SAA may require more than one blood transfusion per week³. An online discrete choice experiment was performed in patients with SAA who had experienced insufficient responses to immunosuppressive therapy (IST) and had transfusion dependence for 3 or more months during the previous 2 years⁴. In this study, patients with SAA agreed mostly that transfusion independence would allow for a reduced burden on healthcare costs, greater control and QoL, reduced fatigue (86.7% noted), and a decreased need for scheduling time around medical appointments (83.3%). In addition, the highest relative importance was for the risk of bleeding (0.30), followed by the risk of infection (0.28), fatigue (0.23), and frequency of transfusions (0.20)⁴. More frequent transfusions resulted in lower healthcare utility, which highlight the significant challenges that patients with SAA face on a daily basis.

Few therapeutic options are currently available for patients with SAA who are ineligible for allogeneic hematopoietic stem cell transplantation (HSCT) or refractory to IST. Allogeneic bone marrow transplantation offers the possibility for cure in younger patients, but most are not suitable candidates for HSCT due to advanced age or lack of an available histocompatible donor^3,5,6. For patients with SAA who do not have a matched related or cannot receive HSCT, primary therapy includes IST, with the combination of antithymocyte globulin (ATG) and calcineurin inhibitors (cyclosporine and tacrolimus)^7–9. A significant proportion of patients though are refractory to IST or relapse after IST^9–13.

Various treatment strategies have been explored in these refractory patients, including a second course of ATG, high-dose cyclophosphamide, and alemtuzumab, and more recently (since August 2014) eltrombopag (EPAG, Promacta Novartis Pharmaceuticals Corp., East Hanover, New Jersey, USA). EPAG, a thrombopoietin receptor agonist, has recently emerged as a promising agent for patients with refractory aplastic anemia (AA) due to its demonstrated efficacy in restoring trilineage hematopoiesis, an effect that is maintained after drug discontinuation^14–18. Results from a Phase 2 study in patients with AA who were refractory to IST showed that 44% (11/25) experienced a hematologic response at 12 weeks¹⁵. About one third of the patients (36%, 9/25) became transfusion independent (median platelet count increase of 44,000 per cubic millimeter)¹⁵. A follow-up extension study, which added 18 patients (for a total of 43 patients), found the majority of patients who remained on EPAG (14/17) continued to show improvement, and 7 eventually experienced significant increases in neutrophil, red cell, and platelet lineages¹⁴. Five patients with robust response in blood counts had drug discontinued at a median of 28.5 months after entry (range, 9–37 months), and all maintained stable counts at a median of 13 months (range, 1–15 months) when taken off EPAG therapy. In addition, first-line use of EPAG in patients with SAA was recently approved in the US based on trial data that demonstrated clinical efficacy and safety in treatment-naïve patients¹⁶. A Phase 1–2 study examined the responses of patients with SAA to IST plus EPAG at varying times of initiation and treatment duration (Cohort 1 received EPAG from Day 14 to 6 months; Cohort 2 from Day 14 to 3 months; and Cohort 3 from Day 1 to 6 months)¹⁶. The overall response rates at Month 6 were 80% in Cohort 1, 87% in Cohort 2, and 94% in Cohort 3¹⁶. Patients with SAA who experienced a response at Month 6 reported significantly higher levels of physical health and overall health-related QoL than those who had not had a response¹⁶. In a previous study, the high economic burden of SAA was found to be comparable to other blood malignancies, such as acute leukemia¹⁹.

Currently, data on treatment patterns, healthcare resource utilization (HCRU), and direct costs are limited for patients with SAA, particularly those on EPAG therapy^9,17,20. The current study used US claims data to compare HCRU and direct costs before and after the initiation of EPAG among patients with SAA.

Methods

Data source

This retrospective cohort study used real-world data from the Truven Health MarketScan Commercial Claims and Encounter and the Medicare Supplemental and Coordination of Benefits databases^21–23. These databases track information from several million individuals enrolled in commercial health insurance plans across the United States (US) and provide detailed cost (payment) and HCRU information for healthcare services performed in both inpatient and outpatient settings, in addition to standard demographic variables^21–23. All study data were accessed using procedures compliant with the Health Insurance Portability and Accountability Act of 1996. No identifiable protected health information was used in the conduct of this study; therefore, informed consent or institutional review board approval was not required.

Selection of SAA patient population

This patient cohort was a subset from sample of SAA patients in a study described previously (Figure 1)¹⁹. In the previous study, patients were identified and included if they (1) had ≥1 ER visit or hospitalization with a SAA diagnosis which reflected acquired bone marrow failure (See Supplemental Appendix A for detailed list of International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9- and ICD-10-[CM] codes) or ≥2 outpatient SAA diagnosis claims at any position during the identification period; (2) had at least one SAA treatment (i.e. immunosuppressant, HSCT, bone marrow stimulants or EPAG) (See Supplemental Appendix B for detailed list of SAA treatments); (3) had continuous health plan enrollment with medical and pharmacy benefits for 6 months prior to and ≥6 months post to the first SAA treatment or blood transfusion in the identification period; (4) were 2 years or older at their first SAA treatment or blood transfusion during the identification period between 1 July 2014 through 31 December 2017; and (5) did not use any SAA treatment within the 6 months prior to the their first SAA treatment or blood transfusion.

Figure 1. Patient selection. ^aBaseline period: 1 month prior to the index date. ^bFollow-up period: 6 months after the index date. ^cThe first EPAG treatment during the identification period was deemed as index date.

Identifying the EPAG patient cohort

A subgroup of patients treated with EPAG from the above sample were selected for this study based on the following criteria: (1) had at least one EPAG treatment during the identification period (first EPAG use was deemed as index date); (2) were continuously enrolled in medical and pharmacy benefits 1 month prior to the index date (baseline period) and at least 6 months after the index date; and (3) were not treated with EPAG in the 6 months prior to the index date (Figure 1).

Patient demographics and clinical characteristics

Patients were classified as having SAA if they had either an ICD-9-CM code of 284.09, 284.8, 284.89, 284.9 or an ICD-10-CM code of D610, D6101, D6109, D613, D6189, D619 between July 1, 2014 and December 31, 2017 (Supplemental Appendix A). Age, sex, insurance type (Health Management Organization [HMO], and Point of Service [POS] capitation, Fee for Service [FFS]), and geographic region (Northeast, Midwest, South, West) were captured from enrollment data. Baseline clinical characteristics included comorbidities and the Deyo claims-based adaptation of the Charlson Comorbidity Index (CCI) score²⁴. CCI was assessed as a continuous variable captured as the sum of weights related to each comorbid condition in the pre-index period.

Outcome measures

All-cause and SAA-related HCRU and costs

The study outcome measures were monthly all-cause and SAA-related HCRU and costs reported during the follow-up period. All-cause and SAA-related HCRU included hospital admissions per patient per month (PPPM), ER visits PPPM, office visits PPPM, and outpatient visits PPPM. All-cause HCRU also included blood transfusions PPPM; Blood transfusions were classified as whole blood transfusions, transfusion of platelets, or transfusion of red blood cells. Monthly all-cause and SAA-related direct costs included plan-paid medical expenditures for inpatient and outpatient visits, office and ER visits; prescription costs for all-cause and SAA-related medications as well as other and total costs. Capitated costs with a value of 0 or 1 for managed care payers were assigned a value using the FFS median cost. All costs were inflation adjusted to 2018 US dollars using the Consumer Price Index²⁵.

Outpatient resource use included services provided in an outpatient hospital setting, ambulatory surgical center, skilled nursing facility, residential substance abuse center, comprehensive outpatient rehabilitation center, end-stage-renal disease center or outpatient Not Elsewhere Classified center. SAA-related therapies and treatment regimens included a possible combination of the following: HSCT agents, bone marrow stimulants (i.e. darbepoetin, epoetin, filgrastim, pegfilgrastim, sargramostim), EPAG, Anti-thymocyte globulin (ATG) (i.e. lymphocyte IG, anti-thymocyte/thimerosal, lymphocyte immune globulin [rabbit, antithymocyte-equine]), calcineurin inhibitor (i.e. cyclosporine or tacrolimus), androgens (i.e. danazol, fluoxymesterone, methyltestosterone, nandrolone, oxandrolone, oxymetholone, stanozolol, testolactone, testosterone), alemtuzumab, romiplostim, cyclophosphamide, blood transfusion (i.e. any type) (Supplemental Appendix B).

Statistical analyses

Descriptive analysis

Descriptive analyses were conducted for each of the study outcome variables. Frequency and percentages are presented for categorical variables. Mean and standard deviation (SD) are shown for continuous variables. T-tests for paired comparisons were used to analyze the HCRU and costs in the pre- and post-EPAG periods.

Results

Patient selection

Patients with ≥1 ER or inpatient claim with an SAA diagnosis or ≥2 outpatient SAA claims at any position during the identification period from 1 July 2014 to 31 December 2017 (identification period) yielded an original sample of 5,283 (Figure 1). Of these patients, 2,119 patients had ≥1 SAA treatment, 1,349 were continuously enrolled in medical and pharmacy benefits 6 months before and ≥6 months after their first SAA treatment or blood transfusion during the identification period, and 1,343 were ≥2 years of age at their first SAA treatment and blood transfusion during the identification period. At this point, 939 patients remained after we excluded those who used any SAA treatment in the baseline period (6 months before the first SAA treatment). Of those, 96 represented a subset of patients who had ≥1 EPAG treatment during the identification period. Finally, 82 of these patients were continuously enrolled in medical and pharmacy benefits during the 1 month prior to the index date (baseline period) and ≥6 months after the index date.

Baseline demographics and clinical characteristics

Baseline demographics and clinical characteristics (1 month prior to EPAG initiation) are presented in Table 1. The average age of the study population was 50.8 years, with 47.6% males and 52.4% females. The most common comorbid conditions overall were mild liver disease (9.8%), renal disease (6.1%), cerebrovascular disease (4.9%), type 2 diabetes without chronic complications (4.9%), congestive heart failure (2.4%), chronic pulmonary disease (2.4%), and metastatic solid tumor (2.4%). The mean CCI score (SD) overall at baseline was 1.1 (1.7). The South had the highest proportion of patients (38/82, 46.3%) and most of the patients (76/82, 92.7%) had FFS insurance.

Table 1. Baseline demographic and clinical characteristics.

	Overall (N = 82)
Age, yrs, mean (SD)	50.8 (20.6)
Sex, n (%)
Male	39 (47.6)
CCI at baseline, mean (SD)	1.1 (1.7)
Comorbidities, n (%)
Mild liver disease	8 (9.8)
Renal disease	5 (6.1)
Type 2 diabetes without chronic complications	4 (4.9)
Cerebrovascular disease	4 (4.9)
Congestive heart failure	2 (2.4)
Chronic pulmonary disease	2 (2.4)
Metastatic solid tumor	2 (2.4)
Type 2 diabetes with chronic complications	1 (1.2)
Rheumatic disease	1 (1.2)
Moderate to severe liver disease	1 (1.2)
US Region, n (%)
Northeast	11 (13.4)
North Central	16 (19.5)
South	38 (46.3)
West	17 (20.7)
Health insurance, n (%)
FFS	76 (92.7)
HMO and POS capitation	5 (6.1)
Other	1 (1.2)

Abbreviations. CCI, Charlson Comorbidity Index; FFS, fee for service; HCRU, healthcare resource utilization; HMO, health maintenance organization; n, total number within a subcategory; POS, point of service; SD, standard deviation; US, United States; yrs, years.

All-cause healthcare resource utilization: baseline and follow-up period

All-cause and SAA-related HCRU in the baseline (1 month prior to EPAG initiation) and follow-up (at Month 6 after EPAG initiation) periods are summarized in Figures 2(A,B). In the baseline period, the mean all-cause HCRU overall (SD) was 0.44 (0.67) for inpatient visits, 0.53 (1.11) for ER visits, 3.79 (2.96) for office visits, and 5.31 (4.18) for other outpatient visits. The mean monthly all-cause HCRU at Month 6 (SD) (after EPAG initiation) were 0.09 (0.29) for inpatient visits, 0.15 (0.40) for ER visits, 2.77 (2.87) for office visits, and 4.24 (5.20) for other outpatient visits (Figure 2(A)). Office visits and other outpatient visits were the most common HCRU categories overall.

Figure 2. (A) Monthly all-cause HCRU in the baseline period and at month 6. (B) Monthly SAA-related HCRU in the baseline period and at month 6. Abbreviations. ER, emergency room; HCRU, healthcare resource utilization; SAA, severe aplastic anemia. ^aBaseline (1 month before EPAG initiation) monthly all-cause/SAA-related health care utilization. ^bMonth 6 after EPAG initiation monthly all-cause/SAA-related health care utilization in the follow-up period. ^cOutpatient visits were hospital setting or ambulatory surgical center, a skilled nursing facility, a residential substance abuse center, a comprehensive outpatient rehabilitation center, an end-stage-renal disease center or an outpatient Not Elsewhere Classified center.

Differences in all-cause HCRU for treatment-naïve patients with SAA from baseline (1 month prior to EPAG initiation) to follow up at Month 6 (after EPAG initiation) ranged from −1.19 (a 20% reduction, p < .05) for outpatient visits to −0.37 (an 80% reduction) for hospitalizations (p < .01; Supplemental Appendix C). For SAA patients treated with EPAG, the mean number of blood transfusions was reduced from 1.0 at weeks 1–2 to 0.4 at weeks 13–14 to 0.5 at weeks 23–24 (p < .05; Figure 3). All of the five parameters examined (including blood transfusions) showed significant reductions (p < .05) in HCRU at Month 6 after EPAG initiation compared with baseline.

Figure 3. Biweekly whole blood transfusions per patient for SAA patients treated with EPAG. Abbreviation. EPAG, eltrombopag. ^aAt Week 1, patients initiated EPAG treatment.

SAA-related healthcare resource utilization: baseline and follow-up period

The mean SAA-related HCRU for treatment-naïve patients with SAA overall (SD) were 0.16 (0.43) for inpatient visits, 0.12 (0.46) for ER visits, 1.84 (2.21) for office visits, and 2.16 (2.62) for outpatient visits in the baseline period (1 month prior to EPAG initiation) (Figure 2(B)). The mean monthly SAA-related HCRU at Month 6 (SD) (after EPAG initiation) were 0.03 (0.16) for inpatient visits, 0.05 (0.27) for ER visits, 1.91 (2.60) for office visits, and 3.00 (3.71) for outpatient visits (Figure 2(B)).

Differences in SAA-related HCRU at Month 6 after EPAG initiation (follow-up) ranged from −0.14 (an 84% reduction, p < .05) for hospitalizations) to 0.80 (a 39% increase, p > .05) for outpatient visits (Supplemental Appendix C). None of the HCRU categories examined were significantly higher at Month 6 compared with baseline (p > .05).

All-cause direct costs: baseline and follow-up period

The monthly all-cause and SAA-related costs for patients with SAA during the baseline (1 month before EPAG initiation) and follow-up periods (after EPAG initiation) are summarized. The mean all-cause total cost [SD] was $65,117 USD [$113,065] at baseline (1 month before EPAG initiation), with the highest contributors as hospitalizations ($48,197 USD [$107,888] 74.0% of total), outpatient visits ($12,332 [$14,290] 18.9%), and prescription costs ($1,808 USD [$4,310] 2.8%). The all-cause total cost at Month 6 [SD] (after EPAG initiation) was $37,349 USD [$74,222] (Figure 4). The biggest contributors to these high costs [SD] were hospitalizations ($9,342 USD [$51,495] 25.0% of total), outpatient visits ($10,597 USD [$22,673] 28.4%), and prescription costs ($12,898 USD [$18,789] 34.5%).

Figure 4. Monthly all-cause and SAA-related costs at 1 month before EPAG initiation and at month 6 following EPAG initiation. Abbreviations. SAA, severe aplastic anemia; ER, emergency room. ^aBaseline: 1 month before EPAG initiation. ^bFollow-up: month 6 after EPAG initiation. ^cOutpatient visits were hospital setting or ambulatory surgical center, a skilled nursing facility, a residential substance abuse center, a comprehensive outpatient rehabilitation center, an end-stage-renal disease center or an outpatient Not Elsewhere Classified center. ^dOther costs are expenses related to school, homeless shelters, assisted living facilities, group homes, mobile units, temporary lodging, health clinics, places of employment, military treatment facilities, custodial care facilities, adult living facilities, Federal qualified health centers, community mental health centers, intermediate care facilities, physical residential treatment centers, non-residential substance abuse centers, mass immunization centers, State or local public health centers, rural health clinics, independent laboratories, and other miscellaneous costs.

Although prescription costs [SD] were higher at Month 6 (after EPAG initiation) with a $11,045 USD (p < .01) difference, substantial reductions in other costs, such as those for hospitalizations ($40,060 USD, p < .01), ER visits ($733 USD, p < .01) and outpatient visits ($2,043 USD, p > .05), offset those increased costs (Supplemental Appendix D). Therefore, the total all-cause monthly costs were numerically lower at Month 6 (after EPAG initiation) compared with baseline (1 month prior to EPAG initiation) (difference of $29,391 USD, p > .05; Supplemental Appendix D).

SAA-related direct costs: baseline and follow-up period

For SAA patients, the mean total SAA-related cost [SD] at baseline (1 month prior to EPAG initiation) was $37,171 USD [$93,572] (Figure 4). The highest contributors to these high costs [SD] were inpatient visits ($29,218 USD [$89,745] 78.6%), and outpatient visits ($5,795 USD [$10,254] 15.6%). The mean monthly SAA-related total cost [SD] at Month 6 (after EPAG initiation) was $23,531 USD [$38,440] (Figure 4). The highest contributors to these high costs [SD] were prescription costs ($11,474 USD [$17,887] 48.8%) and outpatient visits ($7,241 USD [$14,619] 30.8%).

Reductions in monthly SAA-related costs from baseline (1 month prior to EPAG initiation) and Month 6 (after EPAG initiation) ranged from $26,126 USD (hospitalizations) to −$10,115 USD (prescriptions) (Supplemental Appendix D). Prescription costs [SD] were significantly higher in the Month 6 compared with baseline (difference of $10,115 USD [$18,292]; p < .01). However, these increased costs were offset by reductions in hospitalization costs ($26,126 USD [$97,341]; p < .05). Therefore, the total SAA-related monthly costs were numerically lower at Month 6 compared with baseline (difference $14,565 USD or 37% [$101,466]; p > .05).

Discussion

This retrospective US claims database study examined total and SAA-related HCRU and direct costs among patients diagnosed with SAA before and after initiation of EPAG. HCRU associated with hospitalization (including ER visits) was substantially reduced (up to 84%; p < .05) after EPAG treatment in both the all-cause and SAA-related groups. These reductions resulted in a trend to a shift toward increased outpatient visits for SAA-related HCRU (39%, p > .05 at 1 month before EPAG initiation vs Month 6 after EPAG initiation).

The cost analysis corroborated the findings from the HCRU analysis. Costs associated with hospitalization (including ER visits) showed substantial reductions (up to 87%; p < .02) at Month 6 after EPAG treatment in terms of both the all-cause and SAA-related costs. In the follow-up period, costs shifted from hospitalization to prescriptions, outpatient visits, and office visits. The increases in prescription costs were offset by the substantial reductions in costs due to hospitalization, both in the all-cause and SAA-related cost analysis. These study findings suggest that patients could more readily manage their SAA through office visits and outpatient visits after initiating EPAG treatment.

In their responder model for newly diagnosed SAA patients, Tremblay et al.²⁰ assessed the treatment paths and economic impact of including EPAG and IST (ATG and cyclosporine A) as a first-line treatment and found that use of EPAG therapy as a first-line therapy produced a cost increase of $2,151 per month. First-line drug costs accounted for an increase of $3,032 per month while improvements in response rates led to cost offsets for second-line drugs and provided $824 per month in savings. The current study, which used real-world data from children and adults, showed that EPAG treatment also increased prescription costs, however these were generally offset by reductions in hospitalization and outpatient costs. Tremblay and colleagues²⁰ concluded that high response rates combined with reduced risk of mortality, less reliance on rescue medications, and a low disease incidence should result in reasonable economic consequences with EPAG + IST therapy from the US private payer perspective.

Joshi and colleagues conducted a study in children that used the Pediatric Hospital Information System (PHIS) database to perform a retrospective cohort study of patients admitted to Children’s Hospital Association Hospitals to compare length of stay, billed charges, and inpatient mortality in patients with SAA who received IST compared to Stem Cell Transplantation (SCT)¹⁷. They found the highest costs in each group correlated with prescription costs (37%), nursing and room/operating room (32%) charge codes. In comparison, the current study found the highest SAA-related costs at Month 6 were associated with prescriptions ($11,474/$23,531 [USD]; 48.8%), hospitalization ($3,823/$23,531 [USD]; 16.2%), and outpatient visits ($7,241/$23,531 [USD]; 30.8%). These results suggest that patients (including pediatric patients) in the current study benefited from lower hospitalization costs proportionally.

For younger SAA patients, with a human leukocyte antigen-matched sibling donor, stem cell transplantation is an alternative treatment modality option. However, this type of treatment can be costly for the patient. A US study reported the median total healthcare cost at 100 days ranged from $140,792 for the myeloablative autologous regimen to $289,283 for the myeloablative allogeneic regimen²⁶.

Another study by de Latour and associates⁹ examined HCRU associated with SAA among 40 patients with insufficient response to IST (ATG) in real-world practice settings. The mean age of the patients at diagnosis was 44 years. Almost all patients (95%) received ATG in combination with calcineurin inhibitor (cyclosporine or tacrolimus) as primary therapy for SAA. The most common secondary AA therapies included EPAG (28%) and androgens (15%). About 75% of all patients underwent HSCT and the majority of patients (98%) received RBC or platelet transfusions, with a mean of 2.7 RBC transfusions PPPM and 3.3 platelet transfusions PPPM⁹. These patients had a mean of 0.08 hospitalizations PPPM, 0.03 ER visits PPPM, and 1.1 office visits PPPM. The current study had comparable findings; SAA-related HCRU was 0.16 hospitalizations PPPM, 0.12 ER visits, and 1.84 office visits in the baseline period. The current study found SAA-related HCRU followed a similar trend at Month 6 following EPAG treatment with 0.03 hospitalizations PPPM, 0.05 ER visits, and 1.91 office visits. In a subgroup of patients receiving EPAG, there was a trend in the de Latour study toward a reduction in HCRU and transfusion frequency following the initiation of EPAG. The current study found there was approximately a two-fold decrease in reliance on blood transfusions following EPAG treatment from 1.0 at weeks 1–2 to 0.4 at weeks 13–14 and 0.5 at weeks 23–24.

Patients with SAA often need one or more blood transfusions per week to compensate for the reduced capacity of the bone marrow to produce an adequate supply of blood cells³. While blood transfusions have beneficial effects on SAA patients (reducing bleeding with platelets, increased energy with red cell transfusions), this reliance on blood transfusions can negatively affect quality of life (QoL) (i.e. side effects, inconvenience, transfusion time needed)⁴. While little published information is published on the QoL for patients with SAA, patients in one study generally agreed that transfusion independence would allow for a lower burden of time and costs, greater control and QoL, a decrease in fatigue, and a reduced burden of scheduling and logistics around medical appointments. These findings underscore the importance of a treatment regimen that reduced patient reliance on blood transfusions. As was mentioned above, patients experienced up to an approximately two-fold reduction in their need for blood transfusions following EPAG treatment.

The current study has several limitations. Claims data may not be fully representative of all patients with SAA, and a large proportion of race/ethnicity data may be missing. Patients with SAA were identified in this study using ICD codes, but validation via chart review or clinician survey was not possible. A further limitation of claims data is its inability to ascertain whether a case is truly incident or represents a patient who simply did not present for care over a prolonged period. Because SAA is a rare disease, the sample size for this study was relatively small (82 patients). Secondary databases document paid claims for medications, but may not accurately capture medication adherence and compliance since the database does not document whether the medications were actually taken. The authors acknowledge that the variability in the results is wide, therefore, care must be taken when making generalization from our findings. We did not evaluate the response to EPAG and its relationship to costs. Finally, this study did not compare EPAG patients with those undergoing HSCT, which would be an interesting comparison to explore in future studies.

Conclusions

This analysis underscored the significant burden in HCRU and costs for patients with SAA and identified some important trends. Patients benefited from a substantial reduction in their reliance on blood transfusions following EPAG treatment. All-cause and SAA-related HCRU for hospitalizations were significantly reduced following treatment with EPAG. Prescription costs were higher following treatment; however, these costs were offset by reductions in medical costs (i.e. hospitalization and outpatient costs), resulting in a modest reduction in total all-cause costs and an overall savings with use of EPAG for SAA patients.

Transparency

Declaration of funding

Funding for this study was provided by Novartis Pharmaceuticals Corporation.

Declaration of financial/other relationships

BC was a full-time employee of Novartis Pharmaceuticals Corporation when this study was conducted. QS was a full-time employee of Novartis Pharmaceuticals Corporation when this study was conducted. XL was an employee of KMK Consulting Service and worked at Novartis Pharmaceuticals Corporation as a contracted consultant when this study was conducted. FYL was a full-time employee of Novartis Pharmaceuticals Corporation when this study was conducted. SA was a full-time employee of Novartis Pharmaceuticals Corporation when this study was conducted.

A peer reviewer on this manuscript has disclosed that they receive support from, and consult for, Novartis. A peer reviewer on this manuscript has disclosed that they have been a consultant for Novartis, Amgen, Dova, Sysmex, Octapharma, and Shionogi all of whom have products in development or FDA approved for ITP. They have also served on advisory boards for Novartis, Amgen and Dova and have received research funding from Novartis, Amgen, Rigel, and Sysmex. A peer reviewer on this manuscript has disclosed that they have been a speaker for, and acted in an advisory capacity, for Novartis. This manuscript has been additionally reviewed by an Editorial Board Member for an impartiality verification. The Board Member has disclosed that they hold equity in Matrix45, which has provided consultancy services for Novartis and some of its subsidiaries. By Matrix45 company policy, equity holders cannot hold equity in sponsor/client organizations, nor provide services independently to or receive compensation independently from sponsor/client organizations. The peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

BC, QS, SA, XL, and FL were involved in the conception and design, or analysis and interpretation of the data; the drafting of the paper or revising it critically for intellectual content; and the final approval of the version to be published. All authors agree to be accountable for all aspects of the work.

Acknowledgements

We would like to thank Write All, Inc for the writing and editorial assistance.