Financial Burden of Toxoplasmosis Encephalitis Treatment at a Safety Net Hospital

Abstract

Background

Although the price increase of pyrimethamine in 2015 received heavy media coverage, there is little data regarding specific implications to hospitals and the total costs of treating inpatients with toxoplasmosis encephalitis (TE).

Methods

Utilizing average drug wholesale costs, we estimated the inpatient drug costs of TE drugs three years pre- and post- pyrimethamine price increase in August 2015. The drug regimens and total doses were determined through retrospective chart review of patients living with HIV who received treatment for toxoplasmosis encephalitis while inpatient during this period.

Results

The three-year pre-increase TE drug costs for 66 admissions were estimated at $50,310 compared to a total drug cost of $1,026,006 for 61 admissions post-increase. Pyrimethamine made up 98% of the drug costs post-increase, compared to 57% pre-increase. Pyrimethamine-based regimens were the most frequently used throughout the study period.

Conclusions

The price increase of pyrimethamine in 2015 led to a substantial and unnecessary financial burden to hospitals. This required healthcare systems to shift valuable resources in order to continue to provide medications to a vulnerable patient population. There has been more focus on providing high value care in recent years. Our study highlights the need for further examination of pharmaceutical companies’ arbitrary determination of medication costs and how they contribute to patient care.

Introduction

Pyrimethamine, a drug approved by the Food and Drug Administration in 1953¹, remains a recommended first-line treatment regimen for toxoplasmosis encephalitis (TE) in patients with HIV/AIDS². Prior to 2010, the estimated cost of pyrimethamine was low at $1 per pill³. However, in August 2015, the wholesale price of a tablet of pyrimethamine was raised from $13.50 to $750 when Turing Pharmaceuticals acquired Daraprim®, then the only FDA-approved form of pyrimethamine. This price increase elicited widespread criticism among the media, medical professionals, and politicians – ultimately culminating in Congressional hearings ^{3, 4, 5}. Anecdotal reports suggest its high price has forced many hospitals and insurers to remove pyrimethamine from its formulary, resulting in the use of alternate therapies or having to compound the drug onsite as an affordable alternative⁶. Although there is evidence that trimethoprim-sulfamethoxazole may be a cost-effective alternative option⁷, some providers may be hesitant to make the switch given pyrimethamine is still listed as the preferred therapy. We sought to evaluate the prescribing patterns of pyrimethamine and other TE drugs as well as associated costs at a large public hospital in the three years before and after the price hike.

Methods

Setting and Participants

We performed a retrospective chart review of HIV-positive patients hospitalized and treated for TE at Grady Memorial Hospital (GMH), a large safety net hospital in Atlanta, Georgia. We obtained a list of patient medical record numbers (MRNs) from the Emory University Center for AIDS Research (CFAR) registry for all GMH patients with HIV who had ICD-9 or ICD-10 diagnoses codes for toxoplasmosis (ICD-9: 130.x; ICD-10: B58). We included all inpatient admissions from January 1, 2012 through December 31, 2018 in which patients received drug therapy for TE (both initiation and maintenance). We extracted data on patient demographics, insurance status, clinical course, and TE drug regimens used. All data was entered into a HIPAA compliant online REDCap electronic database⁸. We recorded the formulation and cumulative dose amount for all drugs received for TE treatment while inpatient including pyrimethamine, trimethoprim-sulfamethoxazole, sulfadiazine, clindamycin, and atovaquone. We included drugs only when used with the primary intent of TE treatment as indicated in physician notes.

Drug cost

For each TE drug prescribed, we estimated monthly historical costs by using the median of average wholesale prices from all manufacturers as listed in Micromedex RED BOOK⁹ (Supplemental Table 1). We did not use actual procurement costs as hospital-specific costs were proprietary and not available. We estimated the total cost of TE medications for each admission by using the cumulative dose and formulation received and the median average wholesale price of the formulated medication at the date of medication start. Totaled costs were inclusive of all drugs dispensed during hospitalization for toxoplasmosis encephalitis.

Analysis

We report descriptive statistics to characterize patients, inpatient admissions, and drug costs before and after August 1, 2015, when pyrimethamine prices were increased. Inpatient admissions were stratified by the date of admission. We expressed continuous variables as medians and interquartile ranges and summarized categorical variables as counts and percentages.

Results

Forty-three unique patients were identified with a total of 127 inpatient admissions between 2012 and 2018 during which they received drug therapy for TE. Across both pre- and post- price hike periods, patients were predominantly men (81% and 73%), non-White (94% and 100%) and had low CD4 counts (median CD4 = 14 and 12 cells/mcL).

In the 43 months from January, 2012 through July, 2015 there was 66 admissions for TE treatment, with a total estimated cost of $50,310 for inpatient TE drugs. In the 41 months from August, 2015 through December, 2018 there were 61 admissions, with a total estimated drug cost of $1,026,006 (Figure 1). The median estimated drug cost per admission increased ten-fold, from $458 before August, 2015 to $5,452 afterwards. Median estimated drug costs similarly increased from $54 per inpatient day to $1,363. The price of pyrimethamine accounted for the largest portion of this cost increase – increasing from an average wholesale price of $14.50 for a 25 mg tablet to $900.00 after. In comparison, the price of 500 mg tablet of sulfadiazine increased from $4.03 to $4.42 in the same period. Prior to the price hike, pyrimethamine comprised 57% of the total drug costs. After the price hike, 98% of the total drug costs was spent on pyrimethamine. In both periods, pyrimethamine-based regimens were the most commonly used treatments for TE– accounting for 120 of the 176 medication regimens used (some patients had one or more medication regimens during a given admission, Figure 2). The majority of admissions occurred with Medicaid listed as payor and more than a quarter of admissions had no obvious payor source (Supplemental Table 2).

Figure 1.

Total Estimated Drug Costs Incurred for the Treatment of Toxoplasmosis Encephalitis, Grady Memorial Hospital 2012-2018

Figure 2.

Medication Regimens Used in the Treatment of Toxoplasmosis Encephalitis

Discussion

Over the time period of our study, the estimated drug costs incurred in the treatment of toxoplasmosis encephalitis increased dramatically as the result of the price hike for pyrimethamine – from a total cost of approximately $50,000 for 66 admissions before the price hike to > $1 million for the 61 admissions following. Key findings from our study include 1) TE burden remains high and relatively unchanged in our setting; 2) the cost of TE treatment increased dramatically as a result of the price hike; 3) despite widespread outrage, pyrimethamine-based regimens were still the most commonly used pre- and post-price hike (Figure 2).

At the time of the pyrimethamine price increase, Turing Pharmaceutical defended this action in part by describing the variety of rebates and assistance programs available to insurers, hospitals, and patients that would limit the impact of the 50-fold price increase¹⁰. Specifically, Turing had reported they would cut prices by up to 50% for hospitals¹⁰. However even such a discount would still translate to a 2500% increase from pre-August 2015 costs. Although it is difficult to know the exact price hospitals pay since these are proprietary, it is likely that most hospitals are still paying a substantial amount for pyrimethamine despite the rebates described by Turing. Given the estimated magnitude of the price difference – more than $280,000/year in our hospital – even a fraction of this translates to substantial opportunity costs in clinical care. In comparison, the annual salary of a registered nurse is $80,000/year, a health care social worker is $60,470/year, and a community health worker $46,000/year¹¹. Financing additional staff to improve HIV care would likely yield more tangible outcomes than increasing returns to privately held companies.

A major limitation of our study is the estimation of drug costs using historical, median average wholesale price of dispensed medications- the actual costs faced by our large, public hospital is likely lower. As the drug prices each hospital faces are proprietary, it is impossible to know the true procurement price. This lack of cost transparency not only makes academic medical research difficult, but also hinders policymakers in their overall goal of evaluating health care costs. Despite this limitation, we feel that this study offers important insight into prescription drug use. For example, we found that providers still frequently prescribed pyrimethamine-based regimens even after the marked increase in price. Providers are not typically informed of hospital procurement prices or discounts, therefore this finding likely reflects accurate prescribing behavior. In fact, our finding echoes results of previous studies that have shown providers rarely use medication cost in their decision making.¹²

Another limitation is that this study captures the experience of a single institution – other hospitals may have implemented formulary changes or utilization review to limit the financial impact of the pyrimethamine price increase. For example, after presenting and discussing our study findings with our infectious disease colleagues and antimicrobial stewardship team, our hospital guidance document for the treatment of TE was recently updated to recommend trimethoprim-sulfamethoxazole as the preferred initial treatment in December 2021.

A number of off-patent medications such as pyrimethamine, albendazole, and penicillin have seen high profile price increases over the past years¹³. Pyrimethamine is especially illustrative as it is the subject of a Federal Trade Commission suit alleging anti-competitive practices that has entrenched its pricing power¹⁴. Our study illustrates that even for a relatively rarely-used medication, these increases can represent substantial burdens to health system costs – extracting increasing revenues for private companies without concurrent value added. Given the opportunity costs of these higher prices, US policy makers must consider whether our current price system adequately protects vulnerable patients and delivers value. Policy reforms proposed or implemented have yet to yield fruit – more than five years since this price increase, pyrimethamine continues to be priced at more than $750 per tablet, including at our institution, even after three additional generic manufacturers arrived on market. ^{9, 15}.