Elsevier

Clinical Therapeutics

Volume 35, Issue 4, April 2013, Pages 486-497
Clinical Therapeutics

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Original research
Cumulative Burden of Oral Corticosteroid Adverse Effects and the Economic Implications of Corticosteroid Use in Patients With Systemic Lupus Erythematosus

https://doi.org/10.1016/j.clinthera.2013.03.001Get rights and content

Abstract

Background

Corticosteroids (CSs) are used to treat patients with systemic lupus erythematosus (SLE) and are associated with potential adverse events (AEs). However, few data are currently available on the risk of AEs in CS users in an SLE population.

Objective

To examine AEs related to CS use and costs of treating CS-related AEs in patients with SLE.

Methods

In a retrospective cohort study using claims data (study period: January 1, 2000–June 30, 2010), patients aged ≥18 years having ≥2 SLE-related (International Classification of Diseases, Ninth Revision, Clinical Modification code 710.0x) outpatient or ≥1 inpatient/emergency department claim were identified with an index diagnosis date deemed as the date of first SLE diagnosis. Receipt of CS therapy was assessed within 6 months of the index diagnosis date. Cox models were used to evaluate risk of AEs in CS users and nonusers. Associated costs were computed for AEs where risk was significantly different among the cohorts.

Results

Of 2717 patients with SLE, 989 received CSs and 1728 did not. Users of CSs were ∼1.5 times more likely to develop chronic AEs (sleep disturbances, migraines, cataracts, hypertension, and type 2 diabetes mellitus) and ∼2 times more likely to develop acute AEs (pneumonia, herpes zoster, fungal infections, and nausea/vomiting) compared with CS nonusers. The mean annual cost for managing AEs was $4607 and was highest for diabetes mellitus ($9764), hypertension ($8773), and sleep disturbances ($5599). Applying differences in 1-year event rates (CS user: 58.1%; CS nonuser: 75.1%) to cost estimates yielded an additional $784 per year per CS user to manage known CS-related AEs compared with CS nonusers.

Conclusions

Although CSs are prescribed to control SLE symptoms, these results highlight potential risks and costs associated with their use, which providers/payers should consider when making treatment decisions.

Introduction

Systemic lupus erythematosus (SLE) is a chronic, multisystem, inflammatory autoimmune disease of unknown etiology that may affect any organ in the body.1 It was once considered a rare disease; however, it now seems to be relatively common in certain subpopulations. In the United States, it is estimated that >250,000 individuals have SLE,2 with an annual incidence of 2.2 to 7.6 cases per 100,000 persons.3 Sex and race seem to be significant risk factors for SLE. Specifically, 90% of patients with SLE are female,3 and African American women have the highest reported incidence at 11.4 per 100,000 persons per year.4

Systemic lupus erythematosus is characterized by periods of remission followed by episodes of disease activity that correlate with the need for adjustment in pharmacotherapy.4 Because there is no curative therapy for SLE, one of the main goals of treatment is to prevent disease flares and progression.1, 4 Currently, global immunosuppressive therapies, such as corticosteroid (CS) treatment, are often prescribed to control disease manifestations and symptoms.4

Although clinical outcomes for patients with SLE have improved over the years, partly due to the increased use of CSs, CS use is associated with adverse events (AEs). Specifically, CS use is associated with organ toxicity4 and acute and chronic AEs that can be severe or life-threatening.5 Data from the Healthcare Cost and Utilization Project indicated that CSs were the most common specific cause of AEs, accounting for 10.3% of all drug-related AEs and 141,000 hospital stays in the United States in 2004.6 In the Hopkins Lupus Cohort Study, results indicated that an increasing cumulative CS dose was associated with a significantly (P < 0.05) increased risk of osteoporotic fractures (relative risk [RR] = 1.9; 95% CI, 1.5–2.4), symptomatic coronary artery disease (RR = 1.7; 95% CI, 1.2–2.3), cataracts (RR = 1.7; 95% CI, 1.3–2.1), diabetes (RR = 1.5; 95% CI, 1.0–2.3), pulmonary fibrosis (RR = 1.7; 95% CI, 1.2–2.5), and cognitive impairment/psychosis (RR = 2.0; 95% CI, 1.2–3.2).7

Furthermore, recent data from 2 comprehensive literature reviews indicate that CS use is associated with increased costs. Sarnes et al8 reported that costs for certain AEs were substantial. Specifically, 1-year per-patient costs were up to $21,824.68 for peptic ulcers, $26,471.80 for nonfatal myocardial infarction, and $18,357.90 for fractures.8 Manson et al9 also reported significant costs associated with CS use in which 14,444 AEs were directly attributed to oral CS use, resulting in an annual cost of £84.2 million. Note that one of the major drawbacks of these studies is the lack of control for confounding variables that may, ultimately, bias the results.

Nonetheless, preliminary evidence suggests that there is a relatively high economic burden of treating CS-related AEs. However, the potentially large economic implications of CS use have not been examined in an SLE population, and a clear pattern of increased risk with an increase in CS dose is difficult to obtain based on past studies owing to wide variability in study designs, patient populations, conditions treated, and treatment durations. Considering that CS use in patients with SLE is so prevalent, it is important to ascertain the risks associated with CS use. Therefore, the purpose of this study was to examine the clinical and economic burden associated with CS use. As such, we aimed to assess the risk of CS-related AEs and the associated costs of treating CS-related AEs in CS users in an SLE population.

Section snippets

Data Source

Integrated medical and pharmacy claims from the IMS LifeLink Health Plans Claims Database were used for this study. This database includes longitudinal, integrated, patient-level medical and pharmaceutical claims comprising 5 billion patient observations from across the United States and >70 million patients from >100 health plans, including medical services and prescription drug information across the entire continuum of care. Specifically, inpatient and outpatient diagnoses (by International

Results

A total of 989 patients with SLE who received CSs and 1728 patients with SLE who did not receive CSs met the eligibility criteria and were included. Table I presents the baseline characteristics of the sample. Specifically, CS users were younger and were more likely to be female compared with CS nonusers. In both cohorts, most patients were from the Midwest. Compared with CS nonusers, comorbidity burden as measured by the Charlson comorbidity index was higher for CS users (0.6 vs 0.7; P =

Discussion

One of the aims of this study was to examine whether treatment with CSs is associated with an increased risk of AEs in patients with SLE. These results indicate that there may be an increased risk of AEs for patients with SLE using CSs compared with patients with SLE not using CSs. In general, we found that patients with SLE receiving CSs were ∼1.5 times more likely to develop 5 chronic AEs (hypertension, cataracts, type 2 diabetes mellitus, migraines, and sleep disturbances) and 4 acute AEs

Conclusions

The results of this study suggest that although CSs are frequently prescribed to control symptoms of SLE, there are potential risks of developing acute or chronic AEs associated with their use. In addition, an increase in mean daily CS dose from <7.5 mg to ≥7.5 mg may increase the risk of acute/chronic AEs. Furthermore, CS use among patients with SLE is also associated with additional costs due to the management of CS-related AEs. In the end, patients, providers, and payers should consider

Conflicts of Interest

GlaxoSmithKline and Human Genome Sciences funded the conduct of this study. Dr. Kan, Mr. Bechtel, and Dr. Molta report being employed by GlaxoSmithKline. Mr. Bechtel and Dr. Molta also report owning stock in GlaxoSmithKline. Dr. Dennis is employed by and owns stock in Human Genome Sciences. Dr. Shah and Mr. Chaudhari are employed by Xcenda, and Xcenda received funding from GlaxoSmithKline. Dr. McLaughlin was employed with Xcenda at the time this study was conducted. The authors have indicated

Acknowledgments

We thank Erin Zagadailov, PharmD, MS, for her clinical expertise and assistance in writing this article. All authors contributed equally to the literature search, data interpretation, figure creation, and writing of the manuscript.

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Current affiliation: Bristol-Myers Squibb, Tampa, Florida.

Current affiliation: AbbVie, Chicago, Illinois.

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