Major bleeding risk and healthcare economic outcomes of non-valvular atrial fibrillation patients newly-initiated with oral anticoagulant therapy in the real-world setting

Aims: This study compared the risk for major bleeding (MB) and healthcare economic outcomes of patients with non-valvular atrial fibrillation (NVAF) after initiating treatment with apixaban vs rivaroxaban, dabigatran, or warfarin.

Methods: NVAF patients who initiated apixaban, rivaroxaban, dabigatran, or warfarin were identified from the IMS Pharmetrics Plus database (January 1, 2013–September 30, 2015). Propensity score matching (PSM) was used to balance differences in patient characteristics between study cohorts: patients treated with apixaban vs rivaroxaban, apixaban vs dabigatran, and apixaban vs warfarin. Risk of hospitalization and healthcare costs (all-cause and MB-related) were compared between matched cohorts during the follow-up.

Results: During the follow-up, risks for all-cause (hazard ratio [HR]?=?1.44, 95% confidence interval [CI]?=?1.2–1.7) and MB-related (HR?=?1.57, 95% CI?=?1.0–2.4) hospitalizations were significantly greater for patients treated with rivaroxaban vs apixaban. Adjusted total all-cause healthcare costs were significantly lower for patients treated with apixaban vs rivaroxaban ($3,950 vs $4,333 per patient per month [PPPM], p?=?.002) and MB-related medical costs were not statistically significantly different ($100 vs $233 PPPM, p?=?.096). Risk for all-cause hospitalization (HR?=?1.98, 95% CI?=?1.6–2.4) was significantly greater for patients treated with dabigatran vs apixaban, although total all-cause healthcare costs were not statistically different. Risks for all-cause (HR?=?2.22, 95% CI?=?1.9–2.5) and MB-related (HR?=?2.05, 95% CI?=?1.4–3.0) hospitalizations were significantly greater for patients treated with warfarin vs apixaban. Total all-cause healthcare costs ($3,919 vs $4,177 PPPM, p?=?.025) and MB-related medical costs ($96 vs $212 PPPM, p?=?.026) were significantly lower for patients treated with apixaban vs warfarin.

Limitations: This retrospective database analysis does not establish causation.

Conclusions: In the real-world setting, compared with rivaroxaban and warfarin, apixaban is associated with reduced risk of hospitalization and lower healthcare costs. Compared with dabigatran, apixaban is associated with lower risk of hospitalizations.     

Characterizing the financial burden of pulmonary arterial hypertension within an integrated healthcare delivery system

Abstract

Purpose:

Financial burden associated with providing healthcare to patients with pulmonary arterial hypertension (PAH) is poorly characterized. This study sought to quantify 3-year healthcare expenditures and determine whether expenditures differed between incident and prevalent PAH cases.

Methods:

This was a retrospective cohort study of Kaiser Permanente Colorado (KPCO) patients with confirmed diagnosis of PAH. Included patients were followed from study entry until 3 years, death, or termination of KPCO membership, whichever came first. All expenditures were reported in 2011 US dollars from the KPCO perspective.

Results:

In total, 157 patients were included: 44 (28%) prevalent and 113 (72%) incident cases. Mean age (prevalent vs incident cases) was 61 years vs 67 years and 13.6% vs 27.4% were males. The majority of patients (55%) were classified as WHO Group 1 PAH. Prevalent cases had less follow-up (843 vs 975 days; p?=?0.033). Overall, median total per patient per day (PPPD) and 3-year total expenditures were $56 (interquartile range (IQR?=?$29–$166) and $50,599 (IQR?=?$25,958–$135,535), respectively. After adjustment for patient characteristics and chronic disease burden, median PPPD ($54 vs $56; p?=?0.950) and 3-year ($37,340 vs $55,073; p?=?0.111) total expenditures were equivalent between prevalent and incident cases; however, the risk of death during the 3-year follow-up was lower among incident cases (hazard ratio?=?0.41, 95% CI?=?0.18–0.91). No significant differences were detected in pharmacy, inpatient, medical office, emergency department, or other expenditures. Median PAH specialty medication PPPD expenditures were also equivalent, also ($226 vs $223 among specialty medication users; p?=?0.861).

Conclusion:

Healthcare expenditures related to PAH represent substantial financial burden. Significant differences according to prevalent or incident case status appeared to be driven by median ED and inpatient expenditures; however, PAH specialty medication expenditures represented a substantial cost-driver overall. Future efforts should focus on optimizing care for patients with PAH to avoid unnecessary harm or waste.     

Real-world annualized healthcare utilization and expenditures among insured US patients with acute intermittent porphyria (AIP) treated with hemin

Abstract

Background and aims: Patients with acute intermittent porphyria (AIP) may suffer from acute non-specific attacks that often result in hospitalizations or emergency room (ER) visits. Prior to the recent approval of givosiran (November 2019), hemin was the only FDA-approved therapy for AIP attacks in the US. Our aim was to estimate the annual healthcare utilization and expenditures for AIP patients treated with hemin using real-world data.

Methods: Patients with ≥1 hemin claim and confirmed AIP diagnosis – 1 inpatient claim or 2 outpatient claims ≥30 d apart for AIP (2015–2017) or acute porphyria (prior to 2015) – were identified in MarketScan administrative claims dataset between 2007 and 2017. Continuous enrolment for ≥6 months from confirmed diagnosis was required. A secondary analysis (“active disease population”) limited the sample to adult patients with ≥3 attacks or 10 months of prophylactic use of hemin within a 12-month pre-index period. AIP-related care was defined by hemin use during an attack (daily glucose and/or hemin use) or prophylaxis (non-attack hemin use). Outcomes were annualized and expenditures were inflated to 2017.

Results: Across 10 years, patients with a confirmed AIP diagnosis (N?=?8,877) and ≥1 hemin claim (N?=?164) were restricted by ≥6 months continuous follow-up (N?=?139). AIP patients were mostly female (N?=?112; 81%), had median age of 40 and 3 years average follow-up. Annualized average total expenditures for AIP-related care were $113,477. Annualized average all-cause (any diagnosis) hospitalizations were statistically significantly lower for patients treated with hemin prophylaxis vs. acute treatment (1.0 vs. 2.1; p?<?.001). In the secondary analysis (N?=?27), annualized average total expenditures for AIP-related care were higher ($187,480).

Conclusions: For AIP patients treated with hemin, patients treated for acute attacks may use a greater number of resources compared to patients treated prophylactically.     

Economic burden of skeletal-related events in patients with multiple myeloma: analysis of US commercial claims database

Aims: To estimate incremental healthcare resource utilization (HRU) and costs associated with skeletal-related events (SREs) secondary to multiple myeloma (MM), and HRU and cost differences in patients with one vs multiple SREs.

Methods: Adults with MM diagnosis between January 1, 2010–December 31, 2014, with benefits coverage ≥12 months pre- and ≥6 months post-diagnosis were followed to last coverage date or December 31, 2015, excluding patients with prior anti-myeloma treatment or cancers. SREs were identified by diagnosis or procedure codes (pathological fracture, spinal cord compression, radiation, or surgery to the bone). SRE patients (index?=?first post-diagnosis SRE) were propensity score matched 1:1 to patients without SRE (assigned pseudo-index) using baseline characteristics, and ≥1 month of continuous enrollment after index/pseudo-index date was required. Per-patient-per year (PPPY) HRU and costs (2016?US$) were determined for inpatient, outpatient, emergency department (ED), and outpatient pharmacy services during follow-up. Wilcoxon signed rank for means and McNemar’s tests for proportions were used to assess differences. Negative binomial regression and generalized linear regression analyses estimated differences in HRU and costs, respectively, for the comparison of single vs multiple SREs.

Results: Each cohort included 848 patients (mean age?=?61 – 62 years, 57% male) with no significant differences in pre-index demographic or clinical characteristics between matched cohorts. Versus non-SRE patients, SRE patients had significantly higher PPPY use (p?<?.0001) of inpatient hospitalizations, ED visits, outpatient pharmacy, and higher direct medical costs ($188,723 vs $108,160, p?<?.0001). Adjusted PPPY total costs were $209,820 in patients with multiple SREs; $159,797 in patients with one SRE.

Limitations: SRE misclassification and residual confounding are possible.

Conclusions: Among patients with MM, average annual costs were substantially higher in patients with SRE compared with matched non-SRE patients. The economic burden of SRE increased further with multiple events.     

Healthcare costs in patients with advanced non-small cell lung cancer and disease progression during targeted therapy: a real-world observational study

Aims: To assess healthcare costs during treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and following disease progression in patients with advanced non-small cell lung cancer (NSCLC).

Methods: A retrospective analysis of medical records of US community oncology practices was conducted. Eligible patients had advanced NSCLC (stage IIIB/IV) diagnosed between January 1, 2008 and January 1, 2015, initiated treatment with erlotinib or afatinib (first-line or second-line), and had disease progression. Monthly Medicare-paid costs were evaluated during the TKI therapy period and following progression.

Results: The study included 364 patients. The total mean monthly cost during TKI therapy was $20,106 (95% confidence interval [CI]?=?$16,836–$23,376), of which 47.0% and 42.4% represented hospitalization costs and anti-cancer therapy costs, respectively. Following progression on TKI therapy (data available for 316 patients), total mean monthly cost was $19,274 (95% CI?=?$15,329–$23,218), and was higher in the 76.3% of patients who received anti-cancer therapy following progression than in the 23.7% of those who did not ($20,490 vs $15,364; p?<?.001). Among patients who received it, anti-cancer therapy ($11,198; 95% CI?=?$7,102–$15,295) represented 54.7% of total mean monthly cost. Among patients who did not receive anti-cancer therapy, hospitalization ($13,829; 95% CI?=?$4,922–$22,736) represented 90.0% of total mean monthly cost. Impaired performance status and brain metastases were significant predictors of increased cost during TKI therapy.

Limitations: The study design may limit the generalizability of findings.

Conclusions: Healthcare costs during TKI treatment and following progression appeared to be similar and were largely attributed to hospitalization and anti-cancer therapy. Notably, almost one-quarter of patients did not receive anti-cancer therapy following progression, potentially indicating an unmet need; hospitalization was the largest cost contributor for these patients. Additional effective targeted therapies are needed that could prolong progression-free survival, leading to fewer hospitalizations for EGFR mutation-positive patients.     

Economic burden of comorbid chronic kidney disease and diabetes

Objective: To estimate real-world healthcare utilization and expenditures across the spectrum of chronic kidney disease (CKD), as determined by estimated glomerular filtration rate (eGFR) categories in patients with diabetes.

Methods: This study employed a retrospective cohort study design using the Truven Healthcare and Claims Dataset from 2009–2012. Index date was defined as the first eGFR value during a continuous enrollment period of 24 months. Cohorts of patients were stratified by Kidney Disease: Improving Global Outcomes CKD stage based on eGFR (stages 1: ≥90?mL/min/1.73?m²; 2: 60–89; 3A: 45–59; 3B: 30–44; 4: 15–29; 5: <15). Healthcare expenditures (total patient and payer paid claims) and utilization (number of claims or visits) were estimated 12-months post-index date using generalized linear modeling and negative binomial modeling, respectively, after adjusting for baseline characteristics.

Results: Of 130,098 patients with an index eGFR value and 24-months continuous enrolment, 64,521 (49.59%) were in stage 1 CKD, 47,816 (36.75%) were in stage 2, 13,377 (10.28%) were in stage 3A, 3,217 (2.47%) were in stage 3B, 898 (0.69%) were in stage 4, and 269 (0.21%) were in stage 5. Patients in stages 3A, 3B, and 4 CKD had 1.32 (95% CI?=?1.22–1.43), 1.59 (95% CI?=?1.41–1.80), and 2.65 (95% CI?=?2.23–3.14) times higher rates of diabetes-associated inpatient visits, respectively, compared with stage 1 CKD patients. Patients in stages 3A, 3B, and 4 CKD had increased incremental total annual healthcare expenditures of $1,732 (95% CI?=?$1,109–$2,356), $2,632 (95% CI?=?$1,647–$3,619), and $6,949 (95% CI?=?$5,466–$8,432), respectively, compared with stage 1 CKD patients.

Limitations: The claims data were generated for billing and reimbursement, not for research purposes.

Conclusions: These real-world data suggest an incremental and significant increase in economic burden in diabetes as kidney function declines, starting with moderate (stage 3A) CKD.     

The economic burden of switching targeted disease-modifying anti-rheumatic drugs among rheumatoid arthritis patients

Aims: To estimate real world healthcare costs and resource utilization of rheumatoid arthritis (RA) patients associated with targeted disease modifying anti-rheumatic drugs (tDMARD) switching in general and switching to abatacept specifically.

Materials and methods: RA patients initiating a tDMARD were identified in IMS PharMetrics Plus health insurance claims data (2010–2016), and outcomes measured included monthly healthcare costs per patient (all-cause, RA-related) and resource utilization (inpatient stays, outpatient visits, emergency department [ED] visits). Generalized linear models were used to assess (i) average monthly costs per patient associated with tDMARD switching, and (ii) among switchers only, costs of switching to abatacept vs tumor necrosis factor inhibitors (TNFi) or other non-TNFi. Negative binomial regressions were used to determine incident rate ratios of resource utilization associated with switching to abatacept.

Results: Among 11,856 RA patients who initiated a tDMARD, 2,708 switched tDMARDs once and 814 switched twice (to a third tDMARD). Adjusted average monthly costs were higher among patients who switched to a second tDMARD vs non-switchers (all-cause: $4,785 vs $3,491, p?p?p?p?=?.021), and numerically lower all-cause costs ($4,444 vs $4,741, p?=?0.188). Switchers to TNFi relative to abatacept had more frequent inpatient stays after switch (incidence rate ratio (IRR) = 1.85, p?=?.031), and numerically higher ED visits (IRR = 1.32, p?=?.093). Outpatient visits were less frequent for TNFi switchers (IRR = 0.83, p?Limitations and conclusions: Switching to another tDMARD was associated with higher healthcare costs. Switching to abatacept, however, was associated with lower RA-related costs, fewer inpatient stays, but more frequent outpatient visits compared to switching to a TNFi.     

The real-world economic impact of home-based video electroencephalography: the payer perspective

Abstract

Aims: Electroencephalography (EEG) is an established method to evaluate and manage epilepsy; video EEG (VEEG) has significantly improved its diagnostic value. This study compared healthcare costs and diagnostic-related outcomes associated with outpatient vs inpatient VEEG among patients with epilepsy in the US.

Materials and methods: This study used Truven MarketScan Commercial and Medicare Supplemental claims databases. Patients with a VEEG between July 1, 2013 and December 31, 2016 were identified. Index event was the first VEEG claim, which was used to determine inpatient and outpatient cohorts. Continuous health plan enrollment 6?months pre- and 12?months post-index VEEG was required. Primary outcomes were costs during the index event and 12?months post index. A generalized linear model with gamma distribution and a log link was used to estimate adjusted index and post-index costs.

Results: Controlling for baseline differences, epilepsy-related cost of index VEEG was significantly lower for the outpatient ($4,098) vs the inpatient cohort ($13,821; p?<?0.0001). The cost differences observed at index were maintained in the post-index period. The 12-month post-index epilepsy-related costs were lower in the outpatient cohort ($6,114 vs $12,733, p?<?0.0001). Time from physician referral to index VEEG was significantly shorter in the outpatient cohort (30.6 vs 42.5?days). Patients in the inpatient cohort were also more likely to undergo an additional subsequent follow-up inpatient VEEG (p?<?0.0001).

Limitations: Administrative claims data have limitations, including lack of data on clinical presentation, disease severity, and comprehensive health plan information. Generalizability may be limited to a US insured population of patients who met study criteria.

Conclusions: Index VEEG was less costly in an outpatient vs inpatient cohort, and costs were lower during the follow-up period of 12?months, suggesting that outpatient VEEG can be provided to appropriate patients as a less costly option. There were fewer follow-up tests in the outpatient cohort with similar pre- and post-index diagnoses.     

The economic burden of depression among adults with rheumatoid arthritis in the United States

Aims: Depression is the most frequent comorbidity reported among patients with rheumatoid arthritis (RA). Comorbid depression negatively impacts RA patients’ health-related quality-of-life, physical function, mental function, mortality, and experience of pain and symptom severity. The objective of this study was to assess healthcare utilization, expenditures, and work productivity among patients with RA with or without depression.

Materials and methods: Data from adult patients who had at least two visits each related to RA and depression over a 1-year period were extracted from the Truven Health MarketScan research databases. Outcomes comprised healthcare resource utilization, work productivity loss, and direct healthcare costs comparing patients with RA with depression (n?=?3,478) vs patients with RA without depression (n?=?43,222).

Results: Patients with RA and depression had a significantly greater relative risk of hospitalization and number of all-cause and RA-related hospitalizations, utilization of emergency services, days spent in the hospital, physician visits, and RA-related surgeries compared with RA patients without depression. Patients with RA and depression had a higher risk of and experienced more events and days of short-term disability compared with patients without depression. The incremental adjusted annual all-cause and RA-related direct costs were $8,488 (95% CI = $6,793–$10,223) and $578 (95% CI = –$98–$1,243), respectively, when comparing patients with RA and depression vs RA only.

Limitations: The current analysis is subject to the known limitations of retrospective studies based on administrative claims data.

Conclusions: This study suggested increased healthcare utilization, work productivity loss, and economic burden among RA patients due to comorbid depression. These findings emphasize the importance of managing depression and including depression as a factor when devising treatment algorithms for patients with RA.     

Healthcare costs among men with favorable risk prostate cancer managed with observation strategies versus immediate treatment in an integrated healthcare system

Objective: This study explored short-term healthcare costs of men managed with observation strategies (OBS) vs immediate treatment (IMT) for favorable risk prostate cancer (PCa) from the Geisinger Health System, a single integrated health system in Pennsylvania, as evidence from the community setting is limited.

Methods: A retrospective cohort study was conducted using electronic health records from men aged ≥40 years diagnosed with favorable risk PCa (T1 or 2, PSA ≤15?ng/mL, Gleason ≤7 [3?+?4]) between January 2005 and October 2013. Prostate-specific healthcare costs were compared between the OBS and IMT cohorts in men with ≥3 years of follow-up and available linked claims data. Sub-group analyses focused on those men with low-risk PCa (T1-2a, PSA ≤10?ng/mL, Gleason ≤6). Sensitivity analysis stratified the study sample in three cohorts: OBS, switched from OBS to definitive treatment (OBS switch), and IMT.

Results: A total of 352 patients were included (OBS?=?70 and IMT?=?282). Compared with IMT, OBS resulted in significantly lower cumulative PCa-related healthcare costs for the first 3 years ($15,785 vs $23,177; p-value <.001). The main cost drivers were outpatient procedures. The OBS cohort had the lowest incremental PCa-related healthcare costs in the first 3 years (OBS: $5,011 vs OBS switch: $26,040, net cost savings?=?$21,029, p?p?Conclusions: In favorable risk PCa, half of the patients who initially chose OBS eventually underwent treatment after their PCa diagnosis. As expected, OBS was associated with reduced disease management costs compared with IMT.     

A real-world analysis of healthcare costs and relative risk of hyperprolactinemia associated with antipsychotic treatments in the United States

Abstract

Aims: Antipsychotic medications are associated with an increased risk of hyperprolactinemia, but differ in their propensity to cause this complication. This study aimed to assess the economic burden of hyperprolactinemia, and to compare its risk among adult patients using atypical antipsychotics (AAs) with a mechanism of action associated with no/low vs high/moderate prolactin elevation.

Methods: This retrospective cohort study was based on US Commercial and Medicaid claims databases. Healthcare costs were compared between matched hyperprolactinemia and hyperprolactinemia-free cohorts using a two-part model. Risk of hyperprolactinemia was compared between patients receiving AAs with a mechanism of action associated with no/low (no/low prolactin elevation cohort) vs high/moderate prolactin elevation (high/moderate prolactin cohort) using logistic regression.

Results: In the commercially insured sample, compared to the hyperprolactinemia-free cohort (n?=?499), the hyperprolactinemia cohort (n?=?499) was associated with incremental total healthcare costs of $5,732 ($20,081 vs $14,349; p?=?.004), and incremental medical costs of $3,861 ($13,218 vs $9,357; p?=?.040), mainly driven by hyperprolactinemia-related costs. In the Medicaid-insured sample, compared to the hyperprolactinemia-free cohort, the hyperprolactinemia cohort was associated with incremental total healthcare costs of $10,773 ($30,763 vs $19,990; p?=?.004), and incremental medical costs of $9,246 ($20,859 vs $11,613; p?=?.004), mainly driven by hyperprolactinemia-related and mental health-related costs. The odds of hyperprolactinemia in the no/low prolactin elevation cohort were 4–5-times lower than that in the high/moderate prolactin elevation cohort (odds ratio =0.21; p?<?.001).

Limitations: Hyperprolactinemia may be under-reported in claims data.

Conclusions: Hyperprolactinemia is associated with substantial healthcare costs. AAs associated with no/low prolactin elevation reduce the risk of hyperprolactinemia by 4–5-times compared to AAs associated with moderate/high prolactin elevation. Treatment options with minimal impact on prolactin levels may contribute to reducing hyperprolactinemia burden in AA-treated patients.     

Healthcare resource utilization among commercially insured patients with cold agglutinin disease in the United States

Abstract

Aims: Cold agglutinin disease (CAD) is a rare subtype of autoimmune hemolytic anemia associated with increased thromboembolism risk and early mortality. Healthcare resource utilization (HRU) in CAD has not been reported. We aimed to compare HRU of patients with CAD with a matched non-CAD cohort in the United States.

Materials and methods: Patients with CAD were identified from 2006 to 2016 in the Optum-Humedica database using CAD terms in clinical notes and hematologist review. Patients were required to have Integrated Delivery Network records and ≥6 months’ follow-up before and after the first CAD mention date (index date). Patients with CAD were matched to a non-CAD cohort based on demographics. Multivariate analyses assessed inpatient hospitalizations, outpatient visits, emergency room visits, and transfusion use between cohorts 6 months before and 12 months after the index date.

Results: Of 814 patients with CAD, 410 met inclusion criteria and were matched to 3,390 patients without CAD. Mean age of patients with CAD was 68.0 years; approximately 62% were female. In the 12 months after the index date, mean inpatient hospitalizations (0.83 vs. 0.25), outpatient visits (17.26 vs. 6.77), emergency room visits (0.55 vs. 0.32), and transfusion days (1.05 vs. 0.05) were higher for patients with CAD than the matched non-CAD cohort (all p?<?.0001). Similarly, in the 6 months before the index date, patients with CAD had higher HRU than matched patients without CAD for all measures evaluated.

Limitations: Results of this study are based on patient information from the Optum-Humedica database, which is limited to commercially insured patients and may not represent the overall CAD population.

Conclusions: CAD places a substantial burden on patients and healthcare systems. In addition, the high HRU for patients with CAD observed in the 6 months before diagnosis indicates that disease awareness and better diagnostic practices may be needed.     

The association of pain interference and opioid use with healthcare utilization and costs,and wage loss among adults with osteoarthritis in the United States

Abstract

Aim: To examine associations of opioid use and pain interference with activities (PIA), healthcare resource utilization (HRU) and costs, and wage loss in noninstitutionalized adults with osteoarthritis in the United States (US).

Methods: Adults with osteoarthritis identified from the Medical Expenditure Panel Survey for 2011/2013/2015 were stratified by no-opioid use with no/mild PIA, no-opioid use with moderate/severe PIA, opioid use with no/mild PIA, and opioid use with moderate/severe PIA. Outcomes included annualized total HRU, direct healthcare costs, and wage loss. Multivariable regression analyses were used for comparisons versus no-opioid use with no/mild PIA (referent). The counterfactual recycled prediction method estimated incremental costs. Results reflect weighted nationally representative data.

Results: Of 4,921 participants (weighted n?=?20,785,007), 46.5% had no-opioid use with no/mild PIA; 23.2% had no-opioid use with moderate/severe PIA; 9.6% had opioid use with no/mild PIA; and 20.7% had opioid use with moderate/severe PIA. Moderate/severe PIA and/or opioid use were associated with significantly higher HRU and associated costs, and wage loss. Relative to adults with no/mild PIA, opioid users with moderate/severe PIA were more likely to have hospitalizations, specialist visits, and emergency room visits (all p?<?.001). Relative to the referent, opioid use with no/mild PIA had higher per-patient incremental annual total healthcare costs ($11,672, 95% confidence interval [CI]?=?$11,435–$11,909) and wage loss ($1,395, 95% CI?=?$1,376–$1,414) as did opioid use with moderate/severe PIA ($13,595, 95% CI?=?$13,319–$13,871; and $2,331, 95% CI?=?$2,298–$2,363) (all p?<?.001). Compared with the referent, estimated excess national total healthcare costs/lost wages were $23.3 billion/$1.3 billion for opioid use with no/mild PIA, and $58.5 billion/$2.2 billion for opioid use with moderate/severe PIA.

Limitations: Unobservable/unmeasured factors that could not be accounted for.

Conclusions: Opioid use with moderate/severe PIA had significantly higher HRU, costs, and wage loss; opioid use was more relevant than PIA to the economic burden. These results suggest unmet needs for alternative pain management strategies.