Characteristics and Management of Uncontrolled Gout Prior to Pegloticase Therapy: A 2-year Claims Analysis

Abstract

Objective

Gout is a progressive form of arthritis that causes significant pain and disability. Patients with treatment-refractory (or uncontrolled) gout experience a higher prevalence and severity of comorbidities than those whose gout is controlled. Pegloticase is a recombinant PEGylated uricase indicated for the treatment of gout in patients refractory to conventional therapy. We evaluated the treatment journey of patients with chronic uncontrolled gout before initiation of pegloticase therapy.

Methods

Using IQVIA’s PharMetrics^® Plus database, we conducted a retrospective observational analysis of adults with ≥ 1 pegloticase claim between April 1, 2011, and August 31, 2020. Demographics were assessed at baseline. Clinical outcomes, health care resource utilization (HCRU), and associated costs were compared over two 12-month periods (months 13–24 and 1–12) prior to the first pegloticase claim (index date).

Results

The study included 408 patients. Prevalence of all gout-associated conditions increased between months 1–12 and 13–24 (P < 0.05 for all). The percentage of patients with tophi increased from 15.4% to 61.5%, the percentage with ≥ 1 flare increased from 49% to 84%, and mean number of flares per patient increased from 1.0 to 2.1 (P < 0.0001 for all). The frequency of all categories of HCRU except emergency department visits also increased (P < 0.0001 for all), as did gout-related healthcare utilization (P£0.005).

Conclusions

Patients with uncontrolled gout experienced an increase in the clinical burden of disease and HCRU in the 2 years before the initiation of pegloticase. Earlier patient identification and initiation of potentially effective therapy may help alleviate these burdens.

Plain Language Summary

Gout is a progressive and painful form of arthritis. Patients with uncontrolled gout have a higher risk of other health problems, including high blood pressure, heart disease, and kidney disease, compared to those whose gout is well controlled. Pegloticase is a medication for patients whose gout has not responded to other treatments. In this study, we used health claims data to understand the treatment journey of 408 patients with gout who were treated with pegloticase. In the 2 years before starting pegloticase, patients experienced increasingly severe gout symptoms as well as an increase in other conditions such as high blood pressure and kidney disease. As a result, these patients required progressively more medication, including opioids, and health care resources. These findings confirm that gout is a progressive condition, and that earlier identification of patients whose gout is not controlled is important to relieving the burden of this disease.

Key Summary Points

Gout affects 3.9% of the adult population in the United States, approximately 9.2 million individuals, most of whom are men and the elderly.

This retrospective observational database analysis compared clinical outcomes, health care resource utilization (HCRU), and costs during a 24-month period in adults with ≥ 1 pegloticase claim between April 1, 2011, and August 31, 2020.

Patients with uncontrolled gout had a high and increasing rate of HCRU prior to initiation of pegloticase, underscoring the progressive nature of gout.

The clinical burden of gout significantly increased prior to the index date (first pegloticase claim), as did all-cause and disease-specific HCRU.

Identifying patients earlier to initiate potentially effective therapy may help alleviate associated human and economic burdens.

Introduction

Gout is a progressive form of arthritis that affects 3.9% of the adult population in the United States (US), approximately 9.2 million individuals, most of whom are men and the elderly [1, 2]. Gout is caused by hyperuricemia (high uric acid levels) and deposition of monosodium urate (MSU) crystals throughout the body, including peripheral joints, soft tissues, and organs [2–6]. Gout manifests as recurrent attacks of acute inflammatory arthritis of the peripheral joints [2]. MSU deposits and inflammation can lead to chronic tophaceous gout, which can in turn lead to bone erosion, joint destruction, and significant disability [7].

Gout is associated with a range of comorbidities, including hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, and chronic kidney disease (CKD) [8–10]. Hyperuricemia and inflammation are believed to play a significant role in many of these conditions, including CKD [11], metabolic syndrome [12], and cardiovascular disease [13]. Long-term prospective observational studies have shown patients with gout have significantly higher all-cause and cardiovascular mortality rates compared to patients without any history of gout [14, 15].

The human and economic burdens of gout are considerable. Flares, pain, and associated depression significantly impair patients’ quality of life and productivity [16–18]. In addition, the presence of tophi and frequent flares increases the negative impacts of gout on health-related quality of life [19]. In a cross-sectional survey of 620 patients with gout who responded to the US and European Union versions of the 2010 National Health and Wellness Survey, when compared to patients without tophi, those with tophi were significantly more likely to report impairment at work (mean 16.62% vs. 37.67%, p < 0.001) and in day-to-day activities (mean 33.35% vs. 48.68%, p < 0.001), and also reported more healthcare provider visits (mean 5.71 vs. 7.34, p = 0.065) [19].

American College of Rheumatology (ACR) guidelines recommend a treat-to-target strategy using urate-lowering therapy (ULT) guided by serial measurements of serum urate (SU) levels [3]. However, data from the National Health and Nutrition Examination Survey (NHANES) indicate that two-thirds of US adults with gout do not receive ULT [2]. Up to 15% of patients who are receiving guideline-concordant ULT experience persistent hyperuricemia (SU > 6 mg/dl) with recurrent flares and are considered to have chronic uncontrolled gout [20, 21]. This category includes patients who cannot tolerate ULT or for whom ULT is contraindicated [22].

Patients with chronic uncontrolled gout have a particularly high burden of disease with significant negative effects on health-related quality of life and daily activities [23]. Compared to healthy controls or patients with well-controlled gout, patients with uncontrolled gout experience greater impairments in quality of life [23], higher indirect and total costs, more emergency department (ED) visits, higher presenteeism, greater overall work impairment, and greater activity impairment [21].

Limited data exist on the treatment journey of patients with uncontrolled gout. These patients have longstanding disease and may be in an advanced stage with tophi, pain, and flares due to lack of response to oral ULTs. In such cases, prompt treatment is required to prevent further progression. Pegloticase (Krystexxa^®) is a recombinant pegylated uricase approved by the US Food and Drug Administration in 2010 for the treatment of chronic gout in patients who have not responded to or cannot tolerate conventional oral ULT [24–27]. The objective of this study was to understand the path to pegloticase treatment through retrospective evaluation of a cohort of patients who initiated pegloticase due to non-response/intolerance to oral ULT and were therefore assumed to have uncontrolled gout. We assessed and compared real-world clinical outcomes, HCRU, and medication costs over two 12-month intervals in the 2 years prior to initiation of pegloticase therapy.

Methods

Design

This was a retrospective observational database analysis using the IQVIA PharMetrics^® Plus database, a longitudinal commercial health-plan database of adjudicated integrated medical and pharmacy claims. The database includes enrollment data for national and sub-national health plans as well as self-insured employer groups that encompass approximately 190 million enrollees.

Compliance with Ethical Guidelines

Permission was obtained to access and use the data from the database. As this study was conducted using only de-identified data and did not involve collection, use, or transmittal of individually identifiable data, Institutional Review Board (IRB) approval to conduct this study was not necessary. Analysis of commercially available de-identified secondary data sources is considered exempt from the requirements for “human subjects research” in the US. The analyzed datasets meet the requirements of the Health Insurance Portability and Accountability Act of 1996.

Patients

Eligible patients were adults (≥ 18 years) who had ≥ 1 pegloticase claim between April 1, 2011, and August 31, 2020 (first claim = index date), with continuous enrollment for 24 months prior to the index date (pre-index period). As patients were required to have newly initiated pegloticase at the index date, patients with ≥ 1 pegloticase claim in the 24-month pre-index period were excluded. Patients with incomplete data also were excluded as were those with data-quality issues, defined as missing gender or region, invalid health-plan enrollment dates, or incomplete insurance coverage (e.g., Medicare cost coverage, State Children’s Health Insurance Program coverage benefit, pharmacy benefit without medical benefit).

Baseline demographics were reported as of the index date. Clinical measures and economic outcomes were evaluated over two different 12-month intervals in the 24-month pre-index period (Fig. 1). Interval 1 was months 13–24 prior to the first pegloticase claim; Interval 2 was months 1–12 prior to the first pegloticase claim.

Fig. 1.

Study design. HCRU health care resource utilization

Outcomes

Baseline demographic data collected at index included age, gender, geographic region, payer type, and index year. Clinical outcomes assessed were physician specialty type (at office visit on or closest to index date), Dartmouth-Manitoba version of the Charlson Comorbidity Index (DM-CCI) score—a weighted index that uses comorbidity data to predict mortality risk (higher scores = higher risk) [28, 29], and pre-index prevalence of select conditions of interest, including gout-associated conditions, gout flares, oral ULT, and non-urate lowering gout-related therapies (e.g., pain medication). Gout flares were identified using a claims-based algorithm based on a published definition using medical and pharmacy claims [30]. Similar algorithms have been used by other studies [31, 32]. Patients were considered to have had a gout flare if they had ≥ 1 medical claim with a diagnosis for gout in any position followed by a pharmacy claim for a non-steroidal anti-inflammatory drug, colchicine (excluding probenecid/colchicine combination therapy) or corticosteroid (based on National Drug Codes) or medical claim for adrenocorticotropic hormone, or intra-articular aspiration or injection (based on Current Procedural Terminology [CPT] or Healthcare Common Procedure Coding System [HCPCS] codes) within 7 days following the date of gout diagnosis (including the date of gout diagnosis) or ≥ 1 medical claim with a diagnosis of joint pain followed by a prescription for colchicine (except probenecid/colchicine) within 7 days following the date of gout diagnosis (including the date of gout diagnosis). Gout flares were considered to last up to 30 days; other flares within the 30-day window were considered a single gout flare episode. We assessed the proportion of patients with clinical conditions of interest (cataracts, tophi, urolithiasis, CKD, moderate–severe CKD, bone erosion, obesity, cardiovascular disease [CVD], type 2 diabetes, hypertension, gastrointestinal perforation, anemia) overall and for each 12-month pre-index interval.

The proportion of patients and mean number of services per patient were calculated for all-cause and gout-related HCRU (prescription fill, hospitalization, ED visits, physician office visits, outpatient surgical visit, laboratory/pathology test, outpatient radiology exam, and outpatient ancillary). HCRU was considered gout-related if the claim had a gout diagnosis code in the primary position for hospitalization or a gout diagnosis code in any position for outpatient medical claims, including non-ULT gout-related pharmacological treatments and oral ULT treatment options.

Statistical Analysis

Descriptive statistics were calculated for all relevant study measures. For categorical measures, data frequencies and percentages were provided. For continuous and count variables, findings were presented as the mean, standard deviation (SD), and median. Continuous variables were categorized into intervals, with the distribution of patients for each interval (n, %) provided. For clinical outcomes and HCRU, dependent pair-wise comparisons were made to compare outcomes over Interval 1 (13–24 months prior to the first pegloticase claim) versus Interval 2 (1–12 months prior to first pegloticase claim). Dependent statistical comparisons were conducted using paired t tests and Wilcoxon signed-rank tests for continuous variables and McNemar’s test for categorical variables. A p value of < 0.05 was considered statistically significant. All analyses were based on observed, not projected, data and conducted using SAS® Release 9.4 (SAS, Cary, NC, USA).

Results

Subjects

We identified 1047 patients with ≥ 1 claim for pegloticase between April 1, 2011, and August 31, 2020. Of these, 408 met the inclusion criteria and were included in the analysis (Fig. 2). Most were male (88.5%), with an average age (SD) of 55.2 (11.3) years; 66.9% were between the ages of 45–64 years. Seventy-eight percent had a preferred provider organization health plan. For at least 34.8% of patients, a rheumatologist was associated with initiation of pegloticase therapy (Table 1).

Fig. 2.

Patient flow

Table 1.

Patient demographic characteristics

Characteristics	Overall (N = 408)
Mean (SD) age, years	55.2 (11.3)
Age group (%)
18–34 years	3.4%
35–44 years	13.2%
45–54 years	30.9%
55–64 years	36.0%
65–74 years	11.3%
≥ 75 years	5.1%
Male (%)	88.5%
Region (%)
Northeast	11.5%
Midwest	23.5%
South	51.2%
West	13.5%
Physician specialty (%)
Rheumatology	34.8%
Primary care/internal medicinea	23.8%
Nephrology	3.4%
Otherb	33.3%
Payer type (%)
Commercial	59.1%
Medicaid	1.0%
Medicare risk	10.0%
Self-insured	29.7%
Unknown	0.2%

ED emergency department, SD standard deviation

^aEncompasses internal medicine (may include physicians with specialty credentials, including rheumatology), general practice, family practice, physician assistant, and nurse practitioner

^bIncludes psychiatrists, hospitalists/ED physicians, orthopedic specialists, cardiologists, oncologists, and ophthalmologists

Mean (SD) DM-CCI score was 2.4 (2.4); 27.5% of patients had a DM-CCI score of 0, and 37.3% had a DM-CCI score of > 3 (Table 2). At baseline, the most common pre-specified comorbidities of interest were chronic pain/fibromyalgia (76.5%), osteoarthritis (61.3%), arrhythmia (32.4%), sleep disorders (25.7%), and myocardial infarction/coronary artery disease (25.5%). Patients also had multiple clinical conditions of interest over the 24-month pre-index period, notably hypertension (76.2%), tophi (62.5%), and CKD (34.6%). Prevalence of all conditions of interest increased significantly between Interval 1 (months 13–24) and Interval 2 (months 1–12) prior to the index date (Table 2). The percentage of patients with CKD increased from 22.5% to 31.6%, obesity from 18.9% to 27%, CVD from 21.3% to 28.4%, type 2 diabetes from 23.3 to 28.9%, hypertension from 58.1 to 70.3%, and anemia from 12.5 to 21.6% (all P < 0.05). Notably, the percentage of patients with tophi increased from 15.4% to 61.5% (P < 0.0001), the percentage of patients with ≥ 1 flare increased from 48.5% to 83.8% (P < 0.0001), and the mean number of gout flares per patient increased from 1.0 to 2.1 (P < 0.0001) (Fig. 3).

Table 2.

Comorbidities

Characteristic	Overall (N = 408)
Mean (SD) DM-CCI	2.4 (2.4)
0	27.5%
1	16.2%
2	19.1%
3 +	37.3%
Comorbidities of interest (≥ 5% overall)
Asthma	7.8%
Cardiac arrhythmia	32.4%
Cardiac valvular disease	13.2%
Cerebrovascular disease	10.3%
Chronic pain/fibromyalgia	76.5%
Congestive heart failure	12.3%
COPD	7.4%
Depression	10.3%
Dyslipidemia	55.4%
Liver/GB/pancreatic disease	15.9%
Myocardial infarction/CAD	25.5%
Osteoarthritis	61.3%
Peripheral vascular disease	8.1%
Rheumatoid arthritis	23.3%
Sleep disorders	25.7%
Thyroid disease	17.9%

Gout-related conditions	Interval 1 (Months 13–24)	Interval 2 (Months 1–12)	P value
Tophi	15.4%	61.5%	< 0.0001
Urolithiasis	4.2%	6.9%	0.0278
CKD	22.5%	31.6%	< 0.0001
Moderate to severe CKD (stages 3–5)	15.4%	25.0%	< 0.0001
Obesity	18.9%	27.0%	0.0002
CVD	21.3%	28.4%	0.0003
T2DM	23.3%	28.9%	0.0005
Hypertension	58.1%	70.3%	< 0.0001
Anemia	12.5%	21.6%	< 0.0001
Anemia in chronic diseases	6.6%	12.7%	0.0005
Anemia in CKD	4.2%	7.1%	0.0047

CAD coronary artery disease, CKD chronic kidney disease, COPD chronic obstructive pulmonary disease, CVD cardiovascular disease, DM-CCI Dartmouth–Manitoba version of the Charlson Comorbidity Index, GB gallbladder, SD standard deviation, T2DM type 2 diabetes mellitus

Fig. 3.

a Proportion of patients with at least one gout flare, b mean number of gout flares per person

Gout Treatment

Overall, 57.4% of the patients had one oral ULT (excluding probenecid, which is contraindicated in patients with renal impairment or urolithiasis [3, 33]), 11.3% had ≥ 2 oral ULT (excluding probenecid), and 10.3% had ≥ 1 probenecid claim over the 24-month pre-index period (Fig. 4). The use of all gout-related therapies increased significantly between Interval 1 (months 13–24) and Interval 2 (months 1–12) prior to the index date (Table 3). Notably, the proportion of patients with claims for opioids increased from 52.9% to 60.3% (P < 0.0001) while the proportion of patients with claims for corticosteroids increased from 62.5% to 85.5% (P < 0.0001) (Table 3), indicating a higher burden of pain and inflammation over time.

Fig. 4.

Use of any gout medications. ULT urate-lowering therapy

Table 3.

Claims for gout-related therapy prior to pegloticase initiation (N = 408)

	Interval 1 (Months 13–24)	Interval 2 (Months 1–12)	P value
Oral ULT
≥ 1 claim for allopurinol (%)	26.7%	45.6%	< 0.0001
≥ 1 claim for febuxostat (%)	21.6%	31.6%	< 0.0001
Gout-related therapy pain/anti-inflammatory medication
≥ 1 claim for colchicine (%)	39.5%	63.7%	< 0.0001
≥ 1 claim for opioids (%)	52.9%	60.3%	0.0057
≥ 1 claim for corticosteroids (%)	62.5%	85.5%	< 0.0001
≥ 1 claim for oral corticosteroids (%)	50.2%	75.7%	< 0.0001
≥ 1 claim for injectable corticosteroids (%)	38.5%	53.7%	< 0.0001
Immunomodulators
≥ 1 claim for methotrexate (%)	2.5%	13.5%	< 0.0001

ULT urate-lowering therapy

Health Care Resource Utilization

All-cause HCRU

The frequencies of all categories of HCRU (prescription fill, hospitalization, physician office visit, outpatient surgical visit, laboratory/pathology tests, outpatient radiology exams, and outpatient ancillary), except ED visits, increased significantly between Interval 1 (months 13–24) and Interval 2 (months 1–12) prior to the index date (P < 0.0001) (Fig. 5a). Mean use of all categories of HCRU also increased significantly between Interval 1 (months 13–24) and Interval 2 (months 1–12) (all P < 0.0001) (Fig. 5b).

Fig. 5.

a All-cause HCRU – percentage of subjects, b all-cause HCRU – mean uses. ED emergency department, HCRU health care resource utilization

Gout-related HCRU

For gout-related HCRU, the frequencies of all categories (prescription fill, hospitalization, ED visit, physician office visit, outpatient surgical visit, laboratory pathology test, outpatient radiology exam, and outpatient ancillary) increased significantly between Interval 1 (months 13–24) and Interval 2 (months 1–12) prior to the index date (all P ≤ 0.005) (Fig. 6a). The mean use of all categories of HCRU also increased significantly between Interval 1 (months 13–24) and Interval 2 (months 1–12) (all P ≤ 0.0003) (Fig. 6b).

Fig. 6.

a Gout-related HCRU—percentage of subjects. b Gout-related HCRU—mean uses. ED emergency department, HCRU health care resource utilization

Discussion

This analysis suggests that the prevalence and frequency of gout-related conditions, including flares, increased in the two 12-month intervals preceding initiation of pegloticase, which underscores the progressive nature of the disease and the heavy burden that increases over time in patients with uncontrolled gout. In addition, uncontrolled gout—defined as chronic gout that is refractory to conventional therapy—is associated with a high rate of HCRU that increases over time.

Our findings align with those of a claims analysis by Francis-Sedlak et al., which included 6831 patients with gout (1358 uncontrolled; 5473 controlled) who had received ULT for ≥ 90 days [34]. Compared to patients whose gout was controlled (SU < 6.0 mg/dl), those with uncontrolled gout had a higher prevalence of CKD (32.4% vs. 49.4%, P < 0.001), diabetes (49.9% vs. 54.3%, P = 0.003), and heart disease (45.7% vs. 56.0%, P < 0001) [34]. Patients with uncontrolled gout were also more frequent users of gout therapies and stronger pain/anti-inflammatory medications, including opioids, indomethacin, and glucocorticoids, likely reflecting a higher rate of gout flares requiring treatment [34]. The prevalence of comorbidities in the uncontrolled gout cohort was higher than that observed in our study, which may be attributable to the lower mean age in our study (55.2 vs. 69.1 years) and the preponderance of commercially or self-insured patients in the PharMetrics^® Plus database.

Similarly, data from the 2012 and 2013 US National Health and Wellness Survey on individuals with controlled gout (n = 344), uncontrolled gout (n = 2215), and non-gout controls (n = 126,360) found that those with uncontrolled gout had a higher number of ED visits than those with controlled gout or non-gout controls [21]. However, there were no differences between patients with uncontrolled gout and those with controlled gout for the number of physician visits or number of hospitalizations, and the reported frequency of approximately 12 physician visits over a 12-month period was similar to that reported in our study. Our results also mirror those of a survey conducted by the Alliance for Gout Awareness, which reported that just less than half of the patients visit the ED for gout-related pain [35]. This survey also found that 81% of respondents described their gout as “under control,” despite seeing multiple healthcare providers and trying many different medications to manage their gout [35]. These results suggest that some patients have a limited understanding of gout and its treatment and/or have become inured over time to the pain and limitations associated with their condition.

Although our database did not allow us to examine the clinical factors associated with increased HCRU, we did find that gout-related conditions and HCRU both increased over the time period analyzed. In a systematic review of studies focused on the economic burden of gout, indicators of higher disease severity—including SU level, flare frequency, and the presence of tophi—were all associated with higher total and/or gout-related costs of care [36]. This is consistent with our finding that both disease severity and HCRU increased over time. ED visits can substantially increase costs, and we found that one-third of patients had all-cause ED visits and approximately one-sixth had ED visits in the year prior to pegloticase initiation.

A 2013 analysis found that the cost of care for a gout patient was estimated at > $3000 annually compared to a patient without gout when controlling for comorbid conditions, totaling $4–20 billion in the US in 2006 ($6–30 billion in 2023 when adjusted for inflation) [37]. Suggested areas of improvement in patient care that could reduce costs include better-targeted treatments for acute and recurrent attacks, initiating treatment of hyperuricemia earlier, increasing awareness of adherence to treatment, development of therapies highly selective for controlling hyperuricemia and gouty inflammation, and increasing awareness about gout therapies and guidelines (e.g., ACR) among primary care physicians [37].

Results from the current analysis underscore the progressive nature of gout [38, 39] and the speed with which the disease can worsen over a single year. These data are reinforced by a prospective study in patients with gout that found the severity of disability increased in 28% of patients over 1 year of follow-up, and that worsening was associated with a higher frequency of flares [40]. Baseline pain was also significantly associated with increased limitation of activity [40]. In our analysis, 29.7%–85.5% of patients had claims for pain/anti-inflammatory medications during the 24 months preceding initiation of pegloticase, indicating a high burden of pain for many patients.

Approximately three-fourths of patients in the present study had chronic pain/fibromyalgia; these could not be separated due to data collection methods. However, the majority of patients had osteoarthritis (OA) (61%) and tophi (62%), both of which are associated with chronic pain. While the association between OA and gout is still inconclusive, gout and OA are often coincident [41].

We found that the proportion of patients with tophi increased from 15.4% during months 13–24 to 61.5% during months 1–12. In a separate analysis of gout subjects with and without tophi, those with tophi (a proxy for uncontrolled gout) were more likely to have a prolonged duration of symptoms [42], suggesting that the large increase in patients with tophi in our analysis was due to poorly controlled gout. Furthermore, the presence of tophi was associated with a significantly greater annual rate of decline in the estimated glomerular filtration rate (− 4.8 ml/min/1.73²/year) compared with subjects without tophi (− 0.7 ml/min/1.73²/year; P = 0.039) [42]. Similarly, in a 2018 retrospective cohort study, about 16% of patients with gout developed advanced (stages 3–5) CKD versus 10% of those without gout over a median duration of follow-up of 6 years; the risk of CKD was highest during the first 2 years following gout diagnosis [43]. These results and the analysis reported here further emphasize the burden of uncontrolled gout on patients and the healthcare system. Current ACR guidelines recommend initiation of ULT in patients with two or more flares per year, and conditionally recommends initiation of ULT in patients with CKD and one or more flares per year [3]. In the current study, on average patients experienced one flare per year, which increased to two per year while the proportion with comorbidities increased. These data suggest that patients may be at higher risk of serious health outcomes if they have to wait for effective intervention per the guideline.

This study had several limitations. Results from retrospective studies can only establish associations and not cause-and-effect relationships. Because administrative claims such as those captured in the PharMetrics^® Plus database are developed for health service and payment purposes, the determination of some clinical outcomes may require significant interpretation. The database did not include laboratory data to confirm uncontrolled gout through the persistent elevation of SU levels, nor did it capture information on race, ethnicity, or income level.

As noted earlier, the study sample is largely commercially or self-insured and may not be representative of the uninsured or the Medicare or Medicaid populations. We also were not able to obtain information on HCRU or prescriptions obtained outside of the plan benefit (e.g., over-the-counter drugs) nor was it possible to verify the extent of whether patients took the prescribed medication, as prescription fills may not correlate with doses actually taken. Because the study examined patients who had initiated pegloticase, which is often a last treatment option for uncontrolled gout, these patients possibly had severe uncontrolled disease. Finally, patients were categorized based on oral ULT use in the 24-month pre-index period, but may have received other ULTs prior to that time; therefore, no assumption can be made about the duration of gout or the date of initial diagnosis. However, this analysis used a large group of patients with gout and described the patient journey for 2 years prior to initiation of pegloticase, a drug used almost exclusively for uncontrolled gout.

Conclusions

In this study, patients assumed to have uncontrolled gout experienced an increase in the clinical burden and HCRU prior to the initiation of pegloticase. Overall, the present analysis confirms the progressive nature of this disease, as indicated by significant increases in gout-related morbidities and HRCU. The clinical burden of gout significantly increased from Interval 1 (months 13–24) and Interval 2 (months 1–12) prior to the index date, as did all-cause and disease-specific HCRU. The number and proportion of patients using colchicine or oral corticosteroids increased, as did the proportion of patients with tophi or gout flares. Although randomized, prospective clinical trial data that indicate clinical outcomes and quality of life improve during pegloticase treatment [23, 44], further research is needed to assess HCRU among patients with uncontrolled gout following treatment with pegloticase. Nevertheless, the results reported here suggest that delaying the initiation of potentially effective therapy may result in significant worsening of disease as well as increased HCRU.

Author Contribution

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Robert J. Morlock, Mitchell DeKoven, Stephanie D. Taylor, and Vicotira Divino contributed to the conception, design, data acquisition, analysis, interpretation, writing, reviewing, and editing; Deepan Dalal, Atsuko Powers, Naina Barretto, Robert J. Holt, and Brian LaMoreaux contributed to the conception and design of the study, and writing, reviewing, and editing.

Funding

Horizon Therapeutics (now Amgen Inc.) provided funding for the study, for assistance in the preparation of the manuscript and for the Rapid Service Fee.

Data Availability

Data sharing is not applicable to this article as no datasets were generated during the current study. The IQVIA PharMetrics® Plus database is commercially available.

Declarations

Conflict of Interest

Robert J. Morlock was a consultant for Horizon Therapeutics (now Amgen Inc); Deepan Dalal has no conflicts to report; Victoria Divino and Mitchell DeKoven are employees of IQVIA, which received funding for this study from Horizon Therapeutics (now Amgen Inc); Brian LaMoreaux, Stephanie Taylor, Atsuko Powers, Naina Baretto, and Robert J. Holt were employees and shareholders of Horizon Therapeutics (now Amgen Inc) at the time the study was conducted. Brian LaMoreaux, Atsuko Powers, and Naina Baretto are current employees and shareholders of Amgen Inc.

Ethical Approval

The study used the IQVIA PharMetrics® Plus database, a longitudinal commercial health-plan database of adjudicated integrated medical and pharmacy claims. Because this study was conducted using only de-identified data collected in compliance with Health Insurance Portability and Accountability Act of 1996 regulations and the act’s Omnibus Rule of 2013, informed consent was not necessary, and IRB approval was not sought. The study was conducted according to the Declaration of Helsinki.