Healthcare resource use and cost associated with varying dosages of extended corticosteroid exposure in a US population

Abstract

Aims: To quantify healthcare resource use (HCRU) and costs associated with varying levels of corticosteroid exposure.

Materials and methods: Patients with a diagnosis of selected autoimmune and inflammatory diseases between 1 January 2006 and 30 September 2015 (“study period”) were selected from a de-identified, privately-insured claims database. Patients were stratified into four treatment cohorts based on the dosing and duration of continuous corticosteroid use following disease diagnosis: intermittent use with <60 days of corticosteroid use and ≥60 days of corticosteroid use with low (≤7.5 mg/day), medium (>7.5–≤15 mg/day), or high (>15 mg/day) dosage. Patients were followed from the date of their highest dose episode of corticosteroid use (“treatment index date”) until the earliest of the end of continuous corticosteroid use +30 days, disenrollment from health plan, or the end of the study period (“follow-up period”). HCRU and costs in the follow-up period were compared across treatment cohorts.

Results: Of 78,704 patients who were identified for study inclusion, 29% had extended corticosteroid use lasting ≥60 days, and 71% had intermittent use. On average, patients in the high-dose cohort incurred twice the cost of intermittent users ($68,408 vs $32,690 in annualized total all-cause healthcare costs, USD). Adverse event-related medical costs accounted for ∼40% of medical costs, and were higher than disease-related medical costs for all cohorts with extended corticosteroid exposure. Comparing the high-dose and low-dose cohorts, the smaller savings in disease-related prescriptions ($1,680) occurred along with a much larger cost in adverse event-related spend ($13,464).

Limitations: The impact of corticosteroids may be under-estimated because of conservative follow-up duration, and administrative data may contain inaccuracies in coding.

Conclusions: Steroid use, especially at higher doses, is associated with higher HCRU and costs.

Keywords:

• Extended corticosteroid exposure
• corticosteroids
• healthcare resource use
• costs
• dose-dependent response

JEL classification codes:

• I00
• I19

Introduction

Corticosteroids were identified as potential therapeutic agents for patients with rheumatoid arthritis in the 1950s¹. For these patients with rheumatoid arthritis, corticosteroids suppress autoimmune responses that cause inflammation, functioning as immune inhibitors. Since the initial discovery, various corticosteroids (e.g. prednisone, prednisolone, methylprednisolone, and dexamethasone) have been used to treat various autoimmune and inflammatory diseases, including lupus, asthma, skin conditions, and a number of allergies².

However, despite their beneficial clinical effects, systemic (oral or parenteral) use of these agents has also been associated with serious risks, particularly when used at high doses for prolonged periods^3,4. Adverse events (AEs) associated with systemic corticosteroid use include fractures, cardiovascular disease, impaired immune response and wound healing, alterations in glucose and lipid metabolism, and psychiatric disturbances^5–7. Prior literature suggests that there is a dose effect of corticosteroid use in terms of both therapeutic benefit and AEs^6,8.

Although corticosteroids are relatively inexpensive, little is known about the overall healthcare costs associated with corticosteroid use⁶, especially as they relate to higher doses of corticosteroids. Manson et al.⁵ is one of the few studies that considers the economic burden of corticosteroids, finding that it costs at least £165 per patient per year to treat AEs associated with extended corticosteroid use in a UK population. Furthermore, the burden of corticosteroid use, including associated AEs, has not been well characterized among patients with autoimmune and inflammatory diseases. From exposure length, dosage, AEs, to underlying patient characteristics, it is unclear what aspect of corticosteroid use more significantly impacts the overall burden and costs borne by US payers⁹. To address this research gap, a companion study, using the same de-identified administrative claims records of a privately-insured population as the current study, focused on characterizing the clinical aspect of corticosteroid use in terms of prevalence of and time to AE onset¹⁰. Similar to the current study, this companion study’s characterization was stratified by varying levels and durations of corticosteroid exposure. This current study focused on better understanding the economic burden of extended corticosteroid exposure by assessing healthcare resource use (HCRU) and quantifying all-cause, disease-related, and adverse event-related borne to US commercial payers.

Patients and methods

Data source

This study used de-identified administrative claims from OptumHealth Care Solutions, Inc. The vendor of this database collects, aggregates, and de-identifies this claims data. The keys and algorithms used to create the patient identifiers are not available to the authors. As such, consent was not required. Containing healthcare utilization records of over 19.5 million beneficiaries, this database is a large convenience sample of employees, spouses, dependents, and retirees with commercial insurance from 84 large self-insured US-based companies. The database contains information on age, gender, enrollment history, medical diagnoses, procedures performed, dates and place of service, and payment amounts. Prescription drug claims (including fill dates, national drug codes, and payment amounts) are available for all beneficiaries.

Study design and sample selection

Patients with a diagnosis of a range of autoimmune and inflammatory diseases including select systemic immune disorders, rare diseases, central nervous system conditions, and specific complications of organ transplant between 1 January 2006 and 30 September 2015 (“study period”) were identified using relevant ICD-9-CM diagnosis codes. See the Appendix for list of included conditions, as identified through the clinical input of the authors, who also designed the study. For a given study condition, in addition to at least one corticosteroid prescription, patients were required to have either one or more inpatient admissions with the diagnosis or two or more outpatient/physician office visits with the diagnosis separated by ≥30 days during the study period, in order to qualify for study inclusion. Consistent with the dosing cohort definitions and days of corticosteroid use published in Chen et al.¹¹, patients were then stratified into four mutually-exclusive treatment cohorts based on the dosing and duration of continuous corticosteroid use following disease diagnosis: intermittent use with <60 days of corticosteroid use, and ≥60 days of corticosteroid use with low (≤7.5 mg/day), medium (>7.5 to ≤15 mg/day), or high (>15 mg/day) dosage. Corticosteroid use was evaluated based on prescription drug claims; the analysis included oral and parenteral formulations of both glucocorticosteroids and steroid combinations, but excluded mineralocorticoids. The duration of continuous use was based on the days supply of corticosteroid prescriptions. For multiple prescriptions with less than a 14 day treatment gap, the duration of use begins at the first prescription and ends with the last prescription plus the days supply. To calculate the average daily dose, corticosteroid dosages were converted to prednisone-equivalent dose according to potency and then divided by the duration of the continuous use episode^12–14. Patients were followed from the date of their highest dose episode of continuous corticosteroid use (“treatment index date”) until the earliest of the end of continuous corticosteroid use +30 days, disenrollment from the health plan, or the end of the study period (“follow-up period”).

Finally, patients were required to be at least 18 years of age on the treatment index date and have continuous insurance coverage between the disease and treatment index dates as well as for the 6 months preceding (“baseline period”) and 3 months following the treatment index date. To ensure that all relevant drug and medical claims were captured, the insurance coverage could not be through a Health Maintenance Organization (HMO). Figure 1 illustrates the study design.

Figure 1. Study design schematic.

Study measures

Demographics, including age, gender, geographic region, and clinical characteristics were summarized for patients in the four treatment cohorts during the 6-month baseline period including the index date. Clinical characteristics included the Charlson comorbidity index¹⁵ (a measure of severity of underlying clinical conditions) and other chronic comorbidities (i.e. rheumatic disease, chronic pulmonary disease, renal disease, congestive heart failure).

HCRU and costs were assessed across treatment cohorts in the follow-up period. Number and costs of medical visits were analyzed overall as well as by place of service and by selected specialists. Place of service categories included the following: inpatient, outpatient/physician office, emergency department (ED), and other (e.g. skilled nursing facilities, home health). Known to care for patients with autoimmune diseases, selected medical specialists included pulmonologists, ophthalmologists, cardiologists, rheumatologists, and nephrologists. Additionally, prescription drug use, including that for select non-steroid therapies, and other drugs such as ophthalmic agents, NSAIDs, anti-hypertensives, and anti-depressants were also reported. Adverse event-related HCRU and costs for acute and chronic adverse events (e.g. fractures, fungal infection, sepsis, avascular necrosis, hypertension)⁷ and disease-related HCRU and costs for study conditions were also assessed. We note that, although the terminology is similar, AEs in this study were not identified prospectively as they would in a clinical trial setting.

HCRU and costs were normalized by duration, and were reported per patient per month for prescription use and per patient per year for visits and costs. Direct healthcare costs were assessed from the payer perspective; this analysis did not consider any indirect costs such as productivity loss or loss of employment due to illness. The cost of medical claims for patients above 65 years of age was inflated by five times, since Medicare typically covers 80% of medical services, while patients and Part C plans are responsible for 20% coinsurance for most services in Original Medicare. All costs were inflated to 2015 USD using the medical care component of the Consumer Price Index.

Statistical analyses

Patient characteristics, HCRU, and costs were analyzed descriptively. Statistical comparisons were made between each extended corticosteroid cohort (high, medium, and low dose use) and the intermittent use cohort. Statistical significance was assessed using Chi-squared tests for categorical variables and Wilcoxon signed-rank test for continuous variables. All analyses were conducted using SAS version 9.4¹⁶.

Results

Sample selection

In the OptumHealth Care Solutions database, there were 284,181 patients with at least one inpatient admission or outpatient/physician office visit with a diagnosis for a study condition during the study period (Figure 2). After applying all the selection criteria, 78,704 patients were identified for study inclusion, of whom 71% had intermittent corticosteroid use lasting <60 days, 8.6% had low, 11.0% had medium, and 9.5% had high dose use lasting ≥60 days. On average, patients were followed for ∼4.1 years, ranging from 4.2 years for the intermittent use cohort to 3.7 years for the low-dose cohort.

Figure 2. Selection of corticosteroid patients and treatment cohorts.

Baseline characteristics

Across all the treatment cohorts, a majority of patients were female (66.8%) and were between the age of 55–60 years. Patients in the high dose cohort had higher rates of chronic comorbidities, including rheumatic disease (39.9% vs 23.3%), chronic pulmonary disease (21.4% vs 12.9%), and renal disease (16.0% vs 6.6%), compared with patients in the intermittent use cohort (Table 1). The Charlson Comorbidity Index was also higher for patients in the extended corticosteroid cohorts compared with intermittent corticosteroid users (1.9, 1.6, 1.6 vs 1.1, for high, medium, and low dose, respectively, vs intermittent use).

Table 1. Patient characteristics, resource utilization, and healthcare costs during the baseline period.

	High dose cohort	Medium dose cohort	Low dose cohort	Intermittent use cohort
	(n = 7,440)	(n = 8,643)	(n = 6,735)	(n = 55,886)
Demographics
Age (years), mean (SD, 95% CI)	56.0 (15.1, 55.7–56.4)	59.2 (14.8, 58.9–59.5)	60.1 (15.0, 59.8–60.5)	54.8 (15.1, 54.7–54.9)
Male, % (n, 95% CI)	40.3% (2,995, 39.1–41.4%)	32.6% (2,817, 31.6–33.6%)	31.3% (2,110, 30.2–32.4%)	32.5% (18,184, 32.2–32.9%)
US region, % (n, 95% CI)
Northeast	20.8% (1,546, 19.9–21.7%)	22.5% (1,948, 21.7–23.4%)	22.0% (1,480, 21.0–23.0%)	22.0% (12,305, 21.7–22.4%)
Midwest	25.8% (1,917, 24.8–26.8%)	26.0% (2,244, 25.0–26.9%)	26.8% (1,807, 25.8–27.9%)	24.4% (13,639, 24.1–24.8%)
South	33.0% (2,453, 31.9–34.1%)	32.5% (2,808, 31.5–33.5%)	34.0% (2,288, 32.8–35.1%)	35.8% (19,985, 35.4–36.2%)
West	12.5% (927, 11.7–13.2%)	10.4% (895, 9.7–11.0%)	11.6% (780, 10.8–12.4%)	11.1% (6,184, 10.8–11.3%)
Unknown	8.0% (597, 7.4–8.7%)	8.7% (748, 8.1–9.3%)	5.6% (380, 5.1–6.2%)	6.8% (3,773, 6.5–7.0%)
Clinical characteristics
Charlson Comorbidity Index,  mean (SD, 95% CI)	1.9 (1.9, 1.9–2.0)	1.6 (1.5, 1.6–1.7)	1.6 (1.5, 1.6–1.6)	1.1 (1.5, 1.1–1.1)
Chronic comorbidities, % (n, 95% CI)
Rheumatic disease	39.9% (2,967, 38.8–41.0%)	63.6% (5,497, 62.6–64.6%)	64.9% (4,370, 63.7–66.0%)	23.3% (13,041, 23.0–23.7%)
Chronic pulmonary disease	21.4% (1,590, 20.4–22.3%)	14.9% (1,288, 14.2–15.7%)	12.0% (810, 11.3–12.8%)	12.9% (7,191, 12.6–13.2%)
Renal disease	16.0% (1,194, 15.2–16.9%)	9.5% (820, 8.9–10.1%)	10.7% (718, 9.9–11.4%)	6.6% (3,694, 6.4–6.8%)
Diabetes without chronic complications	11.0% (822, 10.3–11.8%)	10.6% (919, 10.0–11.3%)	10.5% (705, 9.8–11.2%)	9.4% (5,269, 9.2–9.7%)
Congestive heart failure	8.2% (613, 7.6–8.9%)	6.4% (557, 5.9–7.0%)	5.3% (358, 4.8–5.9%)	3.7% (2,067, 3.5-3.9%)
Cerebrovascular disease	6.7% (502, 6.2–7.3%)	5.6% (481, 5.1–6.1%)	5.0% (337, 4.5–5.5%)	4.6% (2,553, 4.4-4.7%)
Peripheral vascular disease	5.6% (416, 5.1–6.1%)	5.7% (496, 5.3–6.3%)	5.4% (364) 4.8–6.0%	3.7% (2,061, 3.5-3.9%)

Abbreviation. SD, Standard deviation.

HCRU during the follow-up period

Across all treatment cohorts, medical visits were largely comprised of outpatient facility visits, while inpatient admissions and emergency department visits were relatively low. High dose corticosteroid patients had, on average, 2.4 more AE-related medical visits per year than intermittent users during the follow-up period, representing a 33% higher level of utilization (Table 2).

Table 2. Patient healthcare costs and resource utilization during the follow-up period.

	High dose cohort (n = 7,440)	Medium dose cohort (n = 8,643)	Low dose cohort (n = 6,735)	Intermittent use cohort (n = 55,886)
All-cause medical visits per patient per year, mean (SD)	48.0 (11.4)**	34.8 (8.7)	31.2 (8.3)**	34.8 (9.4)
Inpatient	1.2 (1.4)**	1.2 (1.0)*	1.2 (1.0)*	1.2 (1.0)
Outpatient	36.0 (8.3)**	27.6 (6.6)	25.2 (6.2)**	28.8 (7.3)
Emergency department	2.4 (1.0)**	1.2 (1.0)**	1.2 (0.7)**	1.2 (1.4)
Other visits	8.4 (4.8)**	4.8 (3.5)**	4.8 (3.5)**	3.6 (3.1)
Disease-related visits	10.8 (3.8)**	8.4 (2.4)**	6.0 (2.1)**	4.8 (2.8)
Adverse event-related visits	9.6 (3.8)**	7.2 (3.1)**	6.0 (3.1)**	7.2 (3.5)
≥1 specialist visit, % (n)
Cardiologist	30.2% (2,245)**	24.0% (2,078)*	23.7% (1,597)	22.7% (12,689)
Nephrologist	16.6% (1,237)**	8.4% (726)**	9.0% (604)**	6.3% (3,514)
Ophthalmologist	25.4% (1,892)	23.7% (2,046)**	27.0% (1,821)*	25.6% (14,300)
Pulmonologist	22.8% (1,697)**	11.4% (984)**	9.1% (615)*	10.1% (5,651)
Radiologist	59.2% (4,404)**	52.7% (4,551)*	49.6% (3,342)*	51.1% (28,538)
Rheumatologist	31.9% (2,373)**	51.6% (4,458)**	48.8% (3,289)**	20.8% (11,617)
Number of prescriptions filled per patient per month, mean (SD)	5.5 (3.4)**	5.0 (3.1)**	4.5 (2.9)**	4.0 (2.9)
Number of distinct prescriptions filled per patient per month, mean (SD)	2.9 (1.7)**	2.4 (1.5)**	2.1 (1.3)**	2.7 (2.3)
≥1 prescription filled, % (n)
Select non-steroid therapies	40.2% (2,993)**	55.2% (4,769)**	53.2% (3,583)**	16.6% (9,276)
Other prescription drugs of interest
Anti-hypertensives	37.4% (2,782)**	35.2% (3,039)**	36.2% (2,435)**	27.6% (15,406)
Diuretics	30.8% (2,291)**	25.8% (2,231)**	23.3% (1,571)**	18.5% (10,340)
Anti-anxiety agents	20.6% (1,531)*	16.6% (1,436)**	15.8% (1,061)**	22.0% (12,272)
Anti-depressants	28.5% (2,120)	30.2% (2,610)**	28.5% (1,921)	28.3% (15,799)
Anti-psychotics	6.0% (443)**	3.7% (322)**	2.9% (193)**	4.8% (2,678)
Ophthalmic agents	15.1% (1,127)**	13.9% (1,203)**	15.7% (1,059)**	20.7% (11,586)
Bisphosphonates	12.4% (919)**	13.5% (1,163)**	14.7% (993)**	5.0% (2,779)
NSAIDs	15.7% (1,171)**	26.7% (2,309)**	26.0% (1,750) **	29.2% (16,297)
Healthcare costs per patient per year, mean (SD)
All-cause healthcare costs
Medical costs	$58,079 ($48,326)**	$26,784 ($30,563)**	$23,256 ($26,582)**	$25,236 ($37,210)
Inpatient	$23,724 ($31,033)**	$10,164 ($22,886)	$8,472 ($18,958)**	$8,724 ($28,195)
Outpatient/physician office	$28,396 ($26,852)**	$13,620 ($11,706)**	$12,108 ($12,273)**	$13,836 ($18,131)
Emergency department	$2,208 ($2,379)**	$1,164 ($1,800)**	$900 ($1,617)**	$1,344 ($2,524)
Other visits	$3,768 ($7,371)**	$1,836 ($4,443)**	$1,776 ($4,638)	$1,320 ($3,700)
Prescription drug costs	$10,332 ($6,095)**	$8,724 ($4,861)**	$8,652 ($4,717)**	$7,464 ($4,862)
Total healthcare costs	$68,412 ($49,468)**	$35,496 ($31,534)**	$31,896 ($27,470)**	$32,688 ($37,702)
Adverse event-related medical costs	$22,812 ($30,243)**	$10,632 ($21,605)**	$9,348 ($19,060)**	$8,952 ($26,969)
Disease-related medical costs	$16,152 ($26,656)**	$6,852 ($11,074)**	$5,400 ($12,726)**	$4,128 ($12,003)
Disease-related prescription drug costs	$2,064 ($1,954)**	$3,492 ($2,564)**	$3,744 ($2,475)**	$1,512 ($1,959)

Abbreviation. SD, Standard deviation; *p value <0.05; **p value <0.001.

The extended corticosteroid use cohorts had a notable pattern for the use of select non-steroid therapies, which include immunosuppressive agents, anti-metabolites, alkylating agents, biologic response modifiers, and select interferons, the high-dose cohort had a lower level of use than the medium dose and low dose cohorts (40.2%, 55.2%, and 53.2%, for high, medium, and low dose, respectively). Another notable finding is that less than 15% of all extended-use cohorts had evidence of bisphosphonate use, which is guideline-recommended for the prevention of steroid-induced osteoporosis¹⁷.

Costs during the follow-up period

Higher medical visits and prescription fills incurred by the high dose cohort resulted in total healthcare costs per patient per year that were 2.1-times higher, on average, than those of the intermittent use cohort ($68,412 vs $32,688) (Table 2). Medical costs were driven by outpatient/physician's office visits (∼50% of medical costs across the cohorts) followed by inpatient admissions, ranging from 35% of medical costs for the intermittent use cohort to 41% for the high dose cohort. For most of the costs measures, per patient per year costs increased from the low dose cohort to the high dose cohort.

Across all treatment cohorts, on average, patients experienced higher adverse event-related medical costs per year than disease-related costs. For patients in the extended corticosteroid cohorts, ∼40% of medical costs were adverse-event related and 25% were disease-related.

The cost analysis found that the high-dose extended corticosteroid cohort had a 215% and 244% higher AE-related cost than the medium dose and low dose cohorts (differences of $12,180 and $13,464, respectively), while the disease-related prescription cost was lower for the high-dose cohort by $1,428 and $1,680, respectively (Figure 3).

Figure 3. Annualized healthcare costs. Note, medical cost categories are not mutually exclusive. Abbreviations. AE, adverse event; Rx, prescription.

Discussion

Comparisons of HCRU and costs for patients across corticosteroid treatment cohorts showed a dose-dependent trend. Analysis of HCRU and cost showed that corticosteroid AE-related visits and costs were substantial, with AE-related costs exceeding disease-related costs for all cohorts. AE-related medical costs accounted for 40% of total healthcare costs. AE-related cost in the high-dose extended corticosteroid cohort was 2–2.5-times higher than that of medium dose and low dose cohorts (differences of $12,180 and $13,464, respectively), despite a lower disease-related prescription cost ($1,428 and $1,680, respectively). The trade-off does not appear to be economically equitable.

Few studies have examined the economic burden associated with corticosteroid treatments through primary research. Chen et al.¹¹ studied patients with systemic lupus erythematosus to assess the association between glucocorticoid dosage, HCRU, and costs. High dose patients were found to incur $45,360 in costs in the year after treatment; in comparison, intermittent users incurred $22,940. Ligon and Judson¹⁸ analyzed HCRU for patients with sarcoidosis, and found that patients with greater corticosteroid exposure had significantly more disease-related and AE-related visits. This current study reflects a larger patient population with various autoimmune diseases, including systemic lupus erythematosus and sarcoidosis, and reached the same conclusion, that higher dose corticosteroid use is associated with higher HCRU and costs. This current study, along with the companion study¹⁰, takes the research further by analyzing the breakdown of both HCRU and costs by AE-related and disease-related utilization vs all-cause utilization. This current study found that, among patients in the extended corticosteroid use cohorts, ∼ 40% of their medical costs were associated with AEs, and 25% were disease-related.

This study builds on existing literature by examining the clinical and economic differences across patients with various autoimmune conditions, receiving varying levels of corticosteroid treatment in the US using recent, nationally representative administrative claims data. This study helps address a key research gap and contributes to the understanding of the cost–benefit tradeoff of extended corticosteroid use. Given how large a proportion AE-related costs were found to be, it is important that clinicians carefully consider treatment options for patients with autoimmune and inflammatory diseases that are traditionally treated with corticosteroids. For context, in the current study, over 40% of patients in the extended corticosteroid use cohorts had at least one prescription for a selected non-steroid therapy in the follow-up period, consistent with Chen et al.¹¹.

This study has several limitations, inherent to the data used in the analysis, and the underlying study design. While this study found substantial resource use and costs among patients treated with corticosteroids, it likely understates the actual burden of corticosteroid use in the US. This study assessed resource use and costs from a patient’s highest dose continuous episode of corticosteroid treatment till 30 days after the end of the corticosteroid continuous episode; healthcare resource use and costs may change (and likely increase) due to changes in disease and AE severity beyond the follow-up period evaluated. Further, as with any claims data analysis, this analysis relied on the accuracy of ICD-9 diagnosis codes to identify patients with relevant study conditions and to evaluate their comorbidity profiles at baseline and resource use and cost information during the follow-up period. Similarly, this analysis assumed that patients took the corticosteroid medications as prescribed; adherence to different corticosteroids was not an explicit measure in the current study, but it would be an interesting follow-up analysis.

Additionally, alternative definitions of extended and intermittent steroid use could have been used, as well as follow-up periods of different durations. Given that this was an observational study, no causal relationship between patient characteristics, AEs, and corticosteroid use can be established. As such, the AEs described in the study may be related to underlying patient characteristics or other therapies. Future research should consider adjusted analyses, controlling for confounding factors, particularly disease severity, to allow for a more comprehensive understanding of potential cost drivers. While the association of higher corticosteroid use with higher costs may be expected, given that patients with more severe disease tend to be prescribed more corticosteroids, an important takeaway of the current study is that AE-related costs exceeded disease-related costs. If disease severity was the primary driver of these healthcare costs, disease-related costs would have been expected to significantly exceed AE-related costs. Thus, there are nuanced drivers of costs that are worth exploring further. Finally, as this study was based on a population of commercially-insured beneficiaries in the US, this study’s findings may not be generalizable to other populations.

Conclusions

This study estimated economic burden of corticosteroid use across varying corticosteroid treatment regimens using recent comprehensive administrative claims data. This study’s findings help to further characterize the burden of excessive dosing or duration longer than 60 days of corticosteroid treatment by quantifying the associated healthcare resource use and costs among patients with autoimmune and inflammatory conditions. The study found that patients treated with high dose had higher rates of HCRU and higher medical costs compared to patients who received short-term corticosteroid therapy. AE-related medical costs exceeded that of disease-related medical costs (40% vs 25%). Finally, the savings from corticosteroids as a lower cost prescription option may not offset the much higher AE-related medical costs. The study’s findings support judicious use of corticosteroids to lessen both the associated clinical and economic burden.

Transparency

Declaration of funding

This study was sponsored by Mallinckrodt Pharmaceuticals, Inc., Bedminster, NJ.

Declaration of financial/other relationships

YQ, LBP, GC, and WWN are employees of Mallinckrodt Pharmaceuticals, which provided research funding to Analysis Group, Inc. (employer of JBR, AGW, MJ, and AW). Peer reviewers on this manuscript have received an honorarium from JME for their review work, but have no other relevant financial relationships to disclose.

Previous presentations

Abstracts containing results from this analysis were presented at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting, 3–8 November 2017, San Diego, CA.

Acknowledgments

No assistance in the preparation of this article is to be declared.

Appendix: Diagnosis codes used to identify patients for study inclusion

Table

Condition	ICD-9-CM Diagnosis codes
Select arthropathies, dorsopathies, and related conditions
Ankylosing spondylitis	720.0
Dermatomyositis	710.3
Juvenile chronic polyarthritis	714.3x
Polymyositis	710.4
Rheumatoid arthritis	714.0
Systemic lupus erythematosus	710.0
Select central nervous system conditions
Multiple sclerosis	340
Select infectious conditions
Sarcoidosis	135
Select inflammatory conditions of the skin and subcutaneous tissue
Lupus erythematosus	695.4
Psoriatic arthropathy	696.0
Select malignant neoplasms of lymphoid and histiocytic tissue
Peripheral T cell lymphoma at unspecified extranodal or solid organ site	202.70
Mycosis fungoides	202.1x
Sezary’s disease	202.2x
Select nephrotic conditions
Nephrotic syndrome	581.x
Chronic glomerulonephritis	582.x
Nephritis and nephropathy not specified as acute or chronic	583.x
Proteinuria	791.0
Select disorders of the eye
Sympathetic uveitis	360.11
Panuveitis	360.12
Ophthalmia nodosa	360.14
Retinal (peri) vasculitis	362.18
Focal choroiditis and chorioretinitis, unspecified	363.00
Focal choroiditis and chorioretinitis, juxtapapillary	363.01
Focal choroiditis and chorioretinitis, posterior pole	363.03
Focal choroiditis and chorioretinitis, peripheral	363.04
Focal retinitis and retinochoroiditis, juxtapapillary	363.05
Focal retinitis and retinochoroiditis, macular or paramacular	363.06
Disseminated chorioretinitis, unspecified	363.10
Disseminated choroiditis and chorioretinitis, posterior pole	363.11
Disseminated choroiditis and chorioretinitis, peripheral	363.12
Disseminated choroiditis and chorioretinitis, generalized	363.13
Chorioretinitis, unspecified	363.20
Pars planitis/posterior cyclitis	363.21
Harada’s disease (uveomeningeal syndrome)	363.22
Senile atrophy of choroid	363.41
Acute and subacute iridocyclitis	364.0x
Chronic iridocyclitis	364.1x
Fuch’s heterochromic cyclitis	364.21
Glaucomatocyclitis crisis	364.22
Lens-induced iridocyclitis	364.23
Vogt–Koyanagi syndrome	364.24
Unspecified iridocyclitis uveitis NOS	364.3
Keratitis	370.x
Optic neuritis	377.3x
Ischemic optic neuropathy	377.41
Scleritis and episcleritis	379.0x
Unspecified disorder of eye and adnexa	379.8
Ocular pemphigoid	694.61
Specific complications of organ transplant^1
Complication of transplanted bone marrow, graft-versus-host disease	996.85 and 279.5x
Complications of lung transplant, Bronchiolitis obliterans syndrome	996.84 and 491.8

Abbreviation. ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification.

¹Patients must have evidence of both ICD-9 diagnosis codes listed. Only ICD-9-CM diagnosis codes for the specific complications (i.e. graft-vs-host disease, bronchiolitis obliterans syndrome) that are accompanied (within ±30 days) by a diagnosis code indicating that the condition is a complication of organ transplant will be retained for further sample selection consideration.

Read the corresponding article, “Quantitative Characterization of the Relationship between Levels of Extended Corticosteroid Use and Related Adverse Events in a US Population”, by J. Rice et al, in Current Medical Research and Opinion at 10.1080/03007995.2018.1474090.