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An Analysis of Intravenous Immunoglobin Site of Care: Home Versus Outpatient Hospital
Rakesh Luthra, MS; Ralph Quimbo, MA; Ravi Iyer, PhD; and Michelle Luo, PhD

An Analysis of Intravenous Immunoglobin Site of Care: Home Versus Outpatient Hospital

Rakesh Luthra, MS; Ralph Quimbo, MA; Ravi Iyer, PhD; and Michelle Luo, PhD
This retrospective study compares treatment adherence and healthcare costs for primary immunodeficiency patients receiving intravenous immunoglobulin in home and outpatient settings.
Objectives: To compare treatment outcomes and healthcare costs in a large managed care population for primary immunodeficiency (PI) patients receiving intravenous immunoglobulin (IVIG) in home and outpatient hospital settings.

Study Design: Retrospective observational cohort study.

Methods: This study utilized the HealthCore Integrated Research Database (HIRD) data of nearly 43 million participants in Blue Cross Blue Shield plans. Patients with PI younger than 65 years with at least 1 claim for IVIG between January 1, 2006, and August 31, 2010, with site of care information were identified. Patients with more than 18 IVIG infusions per year or who had evidence of subcutaneous therapy during the study period were excluded. Treatment guidelines and approved dosing recommendations served as proxies for adherence. The differences in adherence levels and costs were examined with a generalized linear model, controlling for baseline Charlson’s Comorbidity Index scores.

Results: Patients with PI were identifi ed in the home (165) and outpatient hospital (179) settings. Optimal adherence (13-18 infusions/year) was greater among home-based (47%) versus outpatient hospital (22%). The mean (± standard deviation [SD]) annual IVIG dose fell in line with the recommended dosing window among patients in home 268 (± 221) grams per patient per year (PPPY) compared with patients treated in outpatient hospital 201 (± 217) grams PPPY. The cost per infusion, in 2010 dollars, was significantly lower in patients treated at home ($3293 vs $4745, P <.001). Mean PPPY hospitalization costs trended lower for patients treated at home ($17,538 vs $20,135).

Conclusions: The study found that home-based patients with PI incurred signifi cantly lower costs per infusion; had signifi cantly higher compliance measured by infusion frequency and average dosing according to IVIG treatment guidelines and dosing recommendations; and their hospitalization and pharmacy costs trended lower.

Am J Pharm Benefits. 2014;6(2):e41-e49
  • Site of care for PI patients receiving immunoglobulin therapy should be taken into consideration as a part of the treatment decision making. 

  • Treatment adherence significantly differs between home and outpatient setting for the PI patients receiving IVIG therapy, suggesting the outcomes benefits of the home care setting. 

  • The potential economic benefits demonstrated in this study including reduced per infusion costs and trended lower hospitalization and pharmacy costs could also provide useful information to assist payers and policy makers in making IG coverage decisions.
Primary immunodeficiency ( PI) is a group of congenital disorders characterized by a genetic defect in either the adaptive or innate immune system.1 Since the first primary immune deficiency (XLA) was defined in 1952, more than 150 other immune disorders have been identified.1,2 The symptoms associated with PI range from mild to life threatening,3 and patients with PI-associated conditions such as hypogammaglobulinemia may face substantial risks of contracting severe and even life-threatening infections.4,5 There are approximately 500,000 cases of PI in the United States, with about 50,000 new cases diagnosed annually.6-8 The incidence of PI is increasing, which may be partly due to increased awareness and diagnosis of the condition.9,10

IVIG, which refers to the intravenous (IV) administration of immunoglobulin (IG), was first approved in the 1980s for the reduction of susceptibility to infections among patients with PI, and later for 5 other indications by the US Food and Drug Administration (FDA).11,12 Among its approved indications, IVIG is prescribed most commonly for PI. It is viewed as continuous therapy, and in most cases it is not discontinued once it is initiated.11 IVIG treatment guidelines, labeling, and dosing studies indicate that PI patients should typically receive IVIG therapy once every 3 to 4 weeks at 300 to 600 mg/kg.13-17

Currently, IVIG therapies are delivered at different sites of care, including physicians’ offices, outpatient departments of hospitals, and at patients’ homes. Following the approval of IVIG, patients were typically treated in hospital settings as a precaution against potential safety issues. With increasing knowledge about the safety profile of IVIG, treatment shifted to outpatient settings, which benefited both administration and monitoring. A successful outpatient track record led to the exploration of home-based treatment, and today, a substantial proportion of patients with PI receive their IVIG therapy routinely at home with the assistance of a nurse.18 An oft-cited benefit of home-based therapy is that it reduces the exposure of immune-compromised patients to pathogens typically associated with hospitals and other public healthcare facilities.19-22 Furthermore, when patients receive services in the home setting, they have greater control over their living activities, and enhanced options for the resumption of normal activities, including work.20-22 The decision about site of care also depends heavily on cost reimbursement considerations and patient convenience,22 in addition to factors such as copay and awareness.

The published literature on infusion therapies in homebased versus outpatient hospital settings is limited. Reduced logistical and travel requirements resulting from home-based delivery of medications such as IVIG could have advantages over outpatient hospital delivery. However, there has been little investigation on site of care, and to the best of our knowledge, none with IVIG. To help address this gap, this retrospective database analysis was conducted to compare real-world treatment outcomes and healthcare costs in a large managed care population of patients with PI receiving IVIG therapy in the home and outpatient hospital settings from a private payer perspective.


Data Source and Study Design

Integrated medical and pharmacy data were used to evaluate differences in healthcare utilization and costs among patients with PI who were treated with IVIG either at home or in an outpatient hospital setting. Study data were queried from the administrative claims repository within the HealthCore Integrated Research Database (HIRD), containing fully adjudicated medical and pharmacy administrative claims for over 43 million benefi - ciaries receiving medical and pharmacy health insurance coverage from Blue Cross Blue Shield plans across 14 states in all geographic regions of the United States. The study period was January 1, 2006, to August 31, 2010. In this longitudinal study, patients were followed from the time they entered the study at the point of initiation of an IVIG therapy (this could be in any calendar year from 2006 to 2010) for the duration of time that they were continuously enrolled.

The researchers only had access to de-identified patient data in this study, and strict measures were observed to ensure that patient anonymity and confidentiality were preserved throughout, in compliance with the Health Insurance Portability and Accountability Act. Current Procedural Terminology (CPT) and Place of Service codes were used to determine the site at which each IVIG treatment was administered—the site was categorized as either home or outpatient hospital, based on their Index IVIG claim. Index IVIG claim was defined as the first claim with evidence of IVIG treatment and site of care information. Index date was defi ned as the date of first claim for IVIG in the study period. Patient demographics and baseline Deyo-Charlson Comorbidity Index (DCI) were compared in both home and outpatient hospital groups, and results were adjusted for these to avoid any potential biases inherent in the selection of either site of care.

Inclusion Criteria

To be included in this study, patients were required to have a diagnosis for PI and no evidence of IVIG therapy 6 months (clean period) prior to the index date. All patients were required to have continuous medical and pharmacy health plan eligibility at least 6 months prior to and after the index date.

Exclusion Criteria

All patients with PI who received subcutaneous therapy at any time in the course of the study duration and patients with no site-of-care information for the IVIG dispensing were excluded from the study. PI patients with more than 18 mean IVIG infusions per year during the study period were excluded from the analysis to be consistent with the IVIG treatment guidelines and dosing recommendation of 1 infusion every 3 to 4 weeks.13-17 This exclusion further filtered out any potential subcutaneous immunoglobulin users. Subjects 65 years and older were excluded to remove patients potentially on Medicare. Anomalous patient costs were analyzed with the Walsh test for outliers and were subsequently excluded from the study, as the high costs were related to chemotherapy and organ transplant, and were not related to IVIG costs.23

Adherence Measure

Commonly used measures such as the medication possession ratio for measuring prescription adherence for pharmaceutical prescription refills are not appropriate for IG therapy because of the intravenous infusion of the drug. Instead, a proxy measure for adherence was utilized based on IVIG treatment guidelines and dosing recommendations, which recommend dosing for patients with PI at 300 to 600 mg every 3 to 4 weeks.13-17 This translates to 13 to 18 infusions per year as the recommended infusion frequency. For the purpose of this study, patients were classified as adherent to therapy if the number of infusions they received per year fell within the recommended infusion frequency. Similarly, dosing compliance was defined as receiving 254 to 507 g/year of IG based on the expected utilization for a 65 kg (143 lb) person receiving 300 to 600 mg/kg every 4 weeks. For pharmacy claims, dose was calculated by multiplying ingredient strength with package size, as obtained from the national drug code description for each IVIG medication. For medical claims, dose was obtained from the CPT code description for each IVIG medication.

Healthcare Cost Analysis

IVIG-related, non–IVIG-related, hospitalization, emergency department (ED), and pharmacy costs were examined specifically. All costs were based on paid claims and were adjusted to 2010 US dollars. Pharmacy costs included paid costs of all drugs received by the patient. IVIG-related costs represented the aggregate of the cost of IVIG drug therapy plus the cost of administration during the study period. We adjusted for comorbidity burden in our analysis of healthcare cost and utilization. Literature shows that patients with comorbidities at baseline typically use more healthcare resources and incur higher costs,24-26 so additional adjustment for baseline costs were not done in the analysis. Non-IVIG costs were assessed as total healthcare costs, less all IVIG-related costs. Hospitalization cost included costs associated with inpatient hospitalization, while pharmacy cost reflected the cost of prescription medication through pharmacy benefits. All costs were annualized by dividing the total costs by the follow-up time for each patient.

Statistical Analysis

All outcome measures were compared between the home-based and outpatient IVIG treatment groups and designed to avoid any potential biases inherent in the selection of either site of care. Study metrics included both descriptive statistics—continuous variables represented by means and standard deviations; and categorical variables represented as percentages—and adjusted results, controlling for baseline DCI scores. The mean DCI scores, an established method used to capture baseline comorbidities, were calculated. The DCI consisted of 17 diagnoses identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes. The Index assigns a weight from 1 through 6 for each comorbid condition diagnosed. The final DCI score represents the sum of the weighted values of the comorbidities that are present; higher scores indicate greater comorbidity burden.27 Significant differences in outcomes were determined with the use of appropriate statistical comparison tests—t test, χ², and analysis of variance. Generalized linear models were used as the basis of regression analyses to assess differences in healthcare resource utilization and costs after controlling for baseline DCI score. Differences in healthcare resource utilization were evaluated with negative binomial distribution fitted with a log link function, while healthcare costs were assessed with Gamma distribution with log link function. All statistical analyses were conducted with SAS 9.2 (Cary, North Carolina) software. Alpha was set at .05 for each test.


Patient Disposition

Medical and pharmacy claims identified 2023 patients with at least 1 claim for IVIG during the study period of January 1, 2006, to August 31, 2010. A total of 344 patients identified with PI met the inclusion and exclusion criteria as shown in Figure 1. Analysis of the data demonstrated that >75% of the study population overall did not change site of care for IVIG therapy administration during follow-up, indicating that there was limited switching between sites of care following the index date.

Demographic Characteristics at Baseline

Of the 344 patients included in this study, 165 received their IVIG treatment at home and 179 in outpatient hospital settings. Of the patients who initiated therapy at home, 87% continued therapy in the home setting for the duration of the study. A lower proportion (69%) continued therapy in the outpatient hospital setting after therapy was initiated in an outpatient hospital. Less than 2% of patients who received IVIG either at home or at an outpatient hospital in this database had a pharmacy claim for IVIG.

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