An Analysis of Intravenous Immunoglobin Site of Care: Home Versus Outpatient Hospital
Published Online: April 15, 2014
Rakesh Luthra, MS; Ralph Quimbo, MA; Ravi Iyer, PhD; and Michelle Luo, PhD
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.
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.
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
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.
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