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 burden associated with thrombocytopenia and platelet transfusions among patients with chronic liver disease

Abstract

Background: Thrombocytopenia (TCP), a common complication of chronic liver disease (CLD), can cause uncontrolled bleeding during procedures. As such, CLD patients with TCP and platelet counts <50,000/μL often receive prophylactic platelet transfusions before invasive procedures. However, platelet transfusions are associated with clinical complications, which may result in increased healthcare utilization and costs.

Objective: This retrospective database analysis describes the clinical and economic burden in CLD patients with TCP, CLD patients without TCP, and CLD patients with TCP who receive platelet transfusions.

Methods: Adult CLD patients with or without TCP were identified in the IBM MarketScan Commercial Claims and Medicare Supplemental data from 1 January 2012 to 31 December 2015. CLD patients with or without TCP were propensity-score matched (1:1) for the analysis of annual healthcare utilization and costs. Platelet transfusions among CLD patients with TCP were identified using procedure codes.

Results: Of the 601,626 patients with CLD, 8,292 (1.4%) patients with TCP were matched to patients without TCP. Among CLD patients with TCP, 981 (11.8%) patients received ≥1 platelet transfusions and met inclusion/exclusion criteria. Compared to patients without TCP, CLD patients with TCP had more complications, including higher prevalence of neutropenia (11.4% vs 2.9%) and bleeding events (21.4% vs 10.9%), greater resource utilization including greater average hospital admissions (1.2 vs 0.7, p?<?.01), greater average ER visits (2.1 vs 1.3, p?<?.01), higher average outpatient office visits (20.1 vs 18.4, p?<?.01), and higher average healthcare costs including total costs (p?<?.01), inpatient costs (p?<?.01), ER visit costs (p?<?.01), and outpatient office visit costs (p?<?.01). The mean annual total costs in CLD and TCP patients with platelet transfusions were $206,396.

Conclusions: CLD patients with TCP, and particularly those who received platelet transfusions, experienced significantly greater clinical and economic burden compared to CLD patients without TCP. Safer and more cost-effective treatments to increase platelets are necessary.     

Comorbidity and economic burden among moderate-to-severe psoriasis and/or psoriatic arthritis patients in the US Department of Defense population

Aims: To examine the comorbidity and economic burden among moderate-to-severe psoriasis (PsO) and/or psoriatic arthritis (PsA) patients in the US Department of Defense (DoD) population.

Materials and methods: This retrospective cohort claims analysis was conducted using DoD data from November 2010 to October 2015. Adult patients with ≥2 diagnoses of PsO and/or PsA (cases) were identified, and the first diagnosis date from November 2011 to October 2014 was defined as the index date. Patients were considered moderate-to-severe if they had ≥1 non-topical systemic therapy or phototherapy during the 12 months pre- or 1 month post-index date. Patients without a PsO/PsA diagnosis during the study period (controls) were matched to cases on a 10:1 ratio based on age, sex, region, and index year; the index date was randomly selected. One-to-one propensity score matching (PSM) was conducted to compare study outcomes in the first year post-index date, including healthcare resource utilization (HRU), costs, and comorbidity incidence.

Results: A total of 7,249 cases and 72,490 controls were identified. The mean age was 48.1 years. After PSM, comorbidity incidence was higher among cases, namely dyslipidemia (18.3% vs 13.5%, p?<?.001), hypertension (13.8% vs 8.7%, p?<?.001), and obesity (8.8% vs 6.1%, p?<?.001). Case patients had significantly higher HRU and costs, including inpatient ($2,196 vs $1,642; p?<?.0016), ambulatory ($8,804 vs 4,642; p?<?.001), emergency room ($432 vs $350; p?<?.001), pharmacy ($6,878 vs $1,160; p?<?.001), and total healthcare costs ($18,311 vs $7,795; p?<?.001).

Limitations: Claims data are collected for payment purposes; therefore, such data may have limitations for clinical research.

Conclusions: During follow-up, DoD patients with moderate-to-severe PsO and/or PsA experienced significantly higher HRU, cost, and comorbidity burden.     

Bronchodilator reliever use and its association with the economic and humanistic burden of COPD: a propensity-matched study

Background and aims: Short-acting bronchodilators are normally used as supplemental relief medication for breakthrough symptoms in COPD patients. The objective of this cross-sectional study was to assess if more frequent vs infrequent use of relief medication in maintenance-treated COPD patients, split by the severity dyspnea, was associated with an increase in the overall disease burden.

Methods: A population-based cross-sectional survey (Adelphi DSP) was conducted among patients with COPD in five European countries. Information was collected on demographic and clinical characteristics, reliever inhaler use, dyspnea (mMRC), health status (CAT, EQ-5D), sleep quality (JSEQ) and healthcare resource use including moderate–severe COPD exacerbations, physician visits, COPD medications and other COPD related resources. The humanistic and economic burden was compared between patients with infrequent reliever use (<1 occasion/week) and more frequent use (≥ 1 occasion/week). The association between increased reliever use and economic burden was also examined after matching patients based on propensity-scores balancing demographic and disease burden characteristics.

Results: Among the 1373 COPD patients prescribed a reliever inhaler, 29% reported using reliever medication ≥1 occasion/week. In the unmatched cohort, more frequent reliever use (n?=?377) compared to infrequent use (n?=?996) was linked to poorer health status (CAT: 25.7 vs 20.0; p?p?p?p?p?=?.0001). In the propensity-score matched population, more frequent reliever use was also associated with significantly higher annual costs for COPD management (€5,034 vs €3,705, p?=?.0327) compared to patients with infrequent reliever use.

Conclusion: In moderate-to-severe COPD, more frequent reliever use is associated with increased exacerbation risk and increased management costs.     

Healthcare resource utilization and direct costs associated with frequent nausea in episodic migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study

Abstract

Background:

Nausea is a common migraine symptom that is associated with impaired quality-of-life and functional disability. In this study, population-based data were used to elucidate the relationship between nausea frequency and headache-related healthcare utilization and costs in persons with migraine.

Research design and methods:

Participants with episodic migraine who completed the 2009 American Migraine Prevalence and Prevention (AMPP) Study survey rated their headache-related nausea as occurring never, rarely, <half the time, or ≥half the time with their headaches, and completed questions on symptom frequency and healthcare resource utilization.

Main outcomes measures:

Ordinal logistic regression models were used to assess the association between nausea frequency and headache-related healthcare utilization. Healthcare cost equivalents were calculated.

Results:

Among the 6488 respondents with episodic migraine, the number of respondents observed across headache-related nausea frequency strata were 6.9% for never, 14.5% for rarely, 29.1% for <half the time, and 49.5% for ≥half the time. In unadjusted models, the odds of having ≥1 healthcare encounter for headache in the preceding year increased with frequency of nausea for primary care/obstetrics-gynecology visits (OR?=?1.41; 95% CI?=?1.30–1.52, p?<?0.001), nurse practitioner/physician assistant visits (OR?=?1.52; 95% CI?=?1.25–1.85, p?<?0.001), neurology/headache clinic visits (OR?=?1.33, 95% CI?=?1.18–1.51, p?<?0.001), pain clinic visits (OR?=?1.31, 95% CI?=?1.01–1.71, p?<?0.05), emergency department visits (OR?=?1.85; 95% CI?=?1.56–2.19, p?<?0.01), and overnight hospital stays (OR?=?1.50, 92% CI?=?1.12–2.00, p?<?0.01). The odds of having ≥1 lifetime CT scan or MRI also increased with the frequency of nausea (p?<?0.001 for both). Results remained significant in these analyses when controlling for sociodemographics and overall symptom severity except in the case of pain clinic visits (p?<?0.107). Visits for Mental Health and visits for Chiropractic/Alternative care did not differ significantly by nausea group in unadjusted or adjusted models. Mean estimated direct headache-related healthcare cost equivalents per person per year generally increased with increasing headache-related nausea frequency across categories of healthcare utilization. Average per person healthcare cost for nausea ≥half the time vs nausea never was $179 and $49 yearly for outpatient services, $183 vs $20 yearly for overnight hospital stays, and $314 vs $257 for lifetime diagnostic services/imaging.

Conclusions:

Direct costs of migraine increase with increasing frequency of migraine-associated nausea. Both frequency and severity of headache-related nausea should be monitored as part of ongoing care of persons with migraine. Headache-related nausea, like headache pain, should be considered an area of central concern during clinical, diagnostic, and treatment optimization assessments.

Study limitations:

This study relied on self-reported headache frequency and healthcare costs which are subject to recall bias and under-reporting; however, reporting bias is unlikely to be different as a function of nausea frequency. In addition, medication use costs and indirect costs (which may be higher than direct costs for migraine) were not assessed.     

Evaluating medical resource utilization and costs associated with thrombocytopenia in chronic liver disease patients

Abstract

Objective:

Thrombocytopenia (TCP), defined as platelet counts <150,000/µL, is a common complication of severe chronic liver disease (CLD). This retrospective study estimated the prevalence of thrombocytopenia in a large population of CLD patients and compared medical resource utilization and medical care costs by TCP status.

Methods:

A retrospective analysis was conducted on a longitudinal administrative claims database from a large US commercial health plan. Patients assigned CLD diagnosis codes from January 1, 2000–December 31, 2003 were identified; annual ambulatory visits, ER visits, inpatient stays, and general and CLD-related medical care costs for patients with vs without TCP (identified using diagnosis codes and platelet count data if available) were compared.

Results:

Of 56,445 patients with an ICD-9-CM diagnosis for CLD, 1289 (2.3%) had a diagnosis for TCP. CLD patients with vs without a TCP diagnosis had >2.5-times the annual number of liver disease-related ambulatory visits (3.6 vs 1.4; odds ratio [OR]?=?2.6, p?<?0.01); were 13-times more likely to have a liver-related inpatient stay (OR?=?13.0, p?<?0.01); were nearly 4-times more likely to have a liver-related ER visit (OR?=?3.9, p?<?0.01); had 3.5-fold greater mean annual overall medical care costs ($43,560 vs $12,270, p?<?0.01); and had 7-fold greater annual liver disease-related medical care costs ($9940 vs $1420, p?<?0.01). Similar results were seen for patients with platelet count data indicating TCP.

Limitations:

CLD and TCP are not always diagnosed, nor is diagnosis uniform or standardized; administrative claims data are subject to coding errors, and individuals covered are not necessarily representative of the general US population. The number of CLD patients in this study with TCP (n?=?1289) is small relative to that expected in the general US population.

Conclusions:

In this analysis, CLD patients with TCP used significantly more medical resources and incurred significantly higher medical care costs than those without TCP.     

Medical resource utilisation and healthcare costs in patients with chronic hepatitis C viral infection and thrombocytopenia

Abstract

Background:

Thrombocytopenia is a significant risk for patients with chronic HCV infection and a common side-effect of treatment with pegylated (PEG) interferon (IFN). Thrombocytopenia predisposes patients to bleeding and requirements for platelet transfusions, and may thus place an increased burden on patients and on medical resource utilisation.

Scope:

In a retrospective analysis of an integrated, longitudinal database of medical and pharmacy claims and laboratory results in a US commercial health (insurance) plan, patients with chronic hepatitis C viral (HCV) infection were identified by reviewing ICD-9-CM HCV-, chronic liver disease-, and cirrhosis-related diagnoses. Medical resource utilisation and laboratory results were evaluated during the year following the HCV diagnosis index date as well as during the baseline year prior to that index date. Medical resource utilisation was determined by comparing outpatient visits, emergency department (ER) visits, and inpatient hospital stays for HCV patients with or without thrombocytopenia.

Findings:

HCV patients diagnosed with thrombocytopenia had a greater incidence of bleeding events (27.3 vs. 9.9%), platelet transfusions (8.5 vs. <1%), liver disease-related ambulatory visits (10.4 vs. 4.4; odds ratio [OR]?=?2.3; p?<?0.001), ER visits (OR?=?8.6; p?<?0.01), and inpatient hospital stays (OR?=?17.7; p?<?0.01) during the study period compared with HCV patients without a thrombocytopenia diagnosis. HCV patients with thrombocytopenia had significantly higher overall healthcare costs ($37,924 vs. $12,174; p?<?0.001) and liver disease-related costs ($14,569 vs. $4107; p?<?0.001) than patients without thrombocytopenia.

Limitations:

Administrative claims data are subject to coding errors; additionally, the patient population may not be completely representative of the general chronic HCV population.

Conclusions:

Diagnosis of thrombocytopenia in patients with HCV is associated with increased incidence of certain comorbidities, complications, and medical interventions, and significantly increased medical resource utilisation.     

Comparative evaluation of treatment patterns and healthcare utilization of newly-diagnosed rheumatoid arthritis patients by anti-cyclic citrullinated peptide antibody status

Background: Anti-cyclic citrullinated peptide (CCP) antibody positivity is an established diagnostic factor for severe disease activity and joint damage and a prognostic factor for aggressive disease in rheumatoid arthritis (RA).

Objective: To compare RA-related treatment, healthcare utilization, and joint erosion between anti-CCP-positive and anti-CCP-negative RA patients.

Methods: Newly-diagnosed RA patients were identified from the Henry Ford Health System database between January 1, 2009 and December 31, 2014; the date of the first RA diagnosis within the study period was the index date. Baseline anti-CCP test was used to categorize patients as anti-CCP-positive or anti-CCP-negative, and outcomes were evaluated in the 6 months post-index.

Results: There were 217 anti-CCP-positive and 191 anti-CCP-negative RA patients included in the study. A higher proportion of anti-CCP-positive patients were initiated on RA treatment than anti-CCP-negative patients (70.5% vs 23.0%; p?<?.0001). More anti-CCP-positive patients received methotrexate (73.2% vs 56.8%; p?=?.0374), while more anti-CCP-negative patients received hydroxychloroquine (31.8% vs 13.1%; p?=?.0037) in first-line therapy. A higher proportion of anti-CCP-negative patients were tested for rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR). Of those tested, there were more positive test results in the anti-CCP-positive cohort compared to the anti-CCP-negative cohort (RF: 84.4% vs 18.2%, p?<?.0001; C-reactive protein [CRP]: 69.7% vs 48.3%, p?=?.0008; and ESR: 89.5% vs 53.9%, p?<?.0001). Outpatient utilization predominated, with more anti-CCP-positive patients having any outpatient physician office visit (96.3% vs 77.5%, p?<?.0001) and a higher mean number of visits (5.3 vs 2.5, p?<?.0001) than anti-CCP-negative patients. Among anti-CCP-positive (n?=?113) and anti-CCP-negative (n?=?58) patients with imaging results, more anti-CCP-positive patients had joint erosion compared to anti-CCP-negative patients (18.6% vs 8.6%; p?=?.0858); however, statistical significance was not reached.

Conclusion: RA patients with positive anti-CCP antibodies had higher degrees of inflammation and disease activity as indicated by laboratory results, which likely contributed to their higher rates of healthcare utilization, joint erosion, and proportions of RA treatment.     

Medical resource utilization and costs for total hip arthroplasty: benchmarking an anterior approach technique in the Medicare population

Aims: The anterior approach (AA) for total hip arthroplasty (THA) is associated with more rapid recovery when compared to traditional approaches. The purpose of this study was to benchmark healthcare resource utilization and costs for patients with THA via AA relative to matched patients.

Materials and methods: This study queried Medicare claims data (2012–2014) to identify patients who received THA via an AA from experienced surgeons, and matched these patients to a control cohort (all THA approaches). Direct and propensity-score matching were employed to maximize similarity between patients and hospitals in the two cohorts. Hospital length of stay (LOS), the proportion of patients discharged to home or home health, and post-acute claim payments during the 90-day episode were assessed. Generalized estimating equations were applied to control for imbalances between the cohorts and clustering of outcomes within hospitals.

Results: A total of 1,794 patients were included after patient matching. Patients who received AA had significantly lower mean hospital LOS vs patients in the control group (2.06?±?1.36 vs 2.98?±?1.58 days, p?<?.0001). The adjusted proportion of patients discharged to home was nearly 20 percentage points higher in the AA cohort vs the control cohort (87.3% vs 68.7%, p?<?.0001). Post-acute claim payments for AA patients were nearly 50% lower than those for control patients ($4,139 vs $7,465, p?<?.0001).

Conclusion: AA patients had significantly lower post-acute care resource use when compared to control patients. Further research is warranted to evaluate the cost effectiveness of AA among surgeons of varying experience levels.     

Healthcare costs,treatment patterns,and resource utilization among pancreatic cancer patients in a managed care population

Abstract

Background:

Pancreatic adenocarcinoma has few effective treatment options and poor survival. The objective of this study was to characterize treatment patterns and estimate the costs and resource use associated with its treatment in a commercially-insured US population.

Methods:

In this retrospective claims-based analysis, individuals ≥18 years old with evidence of pancreatic adenocarcinoma between January 1, 2001 and December 31, 2010 were selected from a managed care database. Treatment phase (either initial non-metastatic or metastatic) was determined using a claims-based algorithm. Patients in the pancreatic cancer population were matched 1:3 to a control population. Resource use (events/person-years), treatment patterns, and healthcare costs (per-patient per-month, PPPM) were determined during a variable length follow-up period (from first pancreatic cancer diagnosis to earliest of death, disenrollment, or study end).

Results:

In this study, 5262 pancreatic cancer patients were matched to 15,786 controls. Rates of office visits, inpatient visits, ER visits, and inpatient stays, and mean total all-cause healthcare costs PPPM ($15,480 vs $1001) were significantly higher among cancer patients than controls (all p?<?0.001). Mean inpatient costs were the single largest cost driver ($9917 PPPM). Also, mean total all-cause healthcare costs were significantly higher during the metastatic treatment phase vs the initial treatment phase of non-metastatic disease ($21,637 vs $10,358, p?<?0.001).

Conclusions:

These results indicate that pancreatic cancer imposes a substantial burden on the US healthcare system, and that treatment of more advanced disease is significantly more costly than initial treatment of non-metastatic disease.

Limitations:

Additional research is needed to validate the accuracy of the claims-based algorithms used to identify the treatment phase.     

Medical resource use and costs associated with chylomicronemia

Abstract

Background:

The prevalence of severe hypertriglyceridemia (TG?>?1000?mg/dl) is estimated at 150–400 per 100,000 individuals in North America. Severe hypertriglyceridemia in the fasting state is associated with increased acute pancreatitis risk and is a sign of chylomicronemia which reflects the accumulation in the bloodstream of chylomicrons, the large lipoprotein particles produced in the gut after a meal.

Objective:

To assess medical resource use and costs associated with chylomicronemia.

Methods:

Patients with chylomicronemia of different causes (≥2 diagnoses with ICD-9 code 272.3) were identified from a large US claims database (years 2000 to 2009) and matched 1:1 to controls free of chylomicronemia based on age, gender, demographics, comorbidities, and use of lipid lowering drugs. During a 1-year study period, medical resource use and costs associated with chylomicronemia or acute pancreatitis were compared between matched cases and controls.

Results:

Among 6472 matched pairs, annual per-patient medical costs, calculated independently of the occurrence of acute pancreatitis, were significantly greater by $808 for chylomicronemia cases vs controls ($8029 vs $7220, p?<?0.01), half of which was attributable to chylomicronemia-related services (p?<?0.01). Chylomicronemia cases with a history of acute pancreatitis (n?=?46) had greater rates of inpatient visits (p?<?0.05) and greater average costs for subsequent acute pancreatitis or abdominal pain (p?<?0.01) as well as greater total medical costs ($33,587 vs $4402, p?<?0.01) vs matched controls. The average episode of acute pancreatitis (n?=?104 episodes) generated medical costs of $31,820, almost entirely due to inpatient stays.

Limitations:

Triglyceride levels were not available to characterize disease severity.

Conclusions:

Patients with chylomicronemia, and especially those with a history of acute pancreatitis, incurred significantly greater total medical costs compared with individuals without chylomicronemia but with an otherwise comparable health profile.     

Medical costs and healthcare resource use in patients with lupus nephritis and neuropsychiatric lupus in an insured population

Abstract

Objective:

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems, including the kidneys (lupus nephritis) and the central nervous system (neuropsychiatric lupus, or NPSLE). The healthcare costs and resource utilization associated with treating lupus nephritis and NPSLE in a large US managed care plan were studied.

Methods:

SLE subjects ≥18 years of age and with claims-based evidence of nephritis or neuropsychiatric conditions were identified from a health plan database. An index date was set as a randomly drawn date from all qualifying claims during 2003–2008 for study subjects. Subjects were matched on the basis of demographic and clinical characteristics to unaffected controls. Costs and resource use were determined during a fixed 12-month post-index period.

Results:

Nine hundred and seven lupus nephritis subjects were matched to controls, and 1062 subjects with NPSLE were matched to controls. Mean overall post-index healthcare costs were significantly higher among subjects with lupus nephritis in comparison to matched controls ($33,472 vs $5347, p?<?0.001). Similarly, mean overall post-index healthcare costs were significantly higher among subjects with NPSLE compared to controls ($30,341 vs $4646, p?<?0.001). Subjects with lupus nephritis or NPSLE had higher mean post-index numbers of ambulatory visits, specialist visits, emergency department visits and inpatient hospital stays, compared to controls (all p?<?0.001).

Limitations:

Additional research, such as medical chart review, could provide validation for the claims-based identification of lupus nephritis and NPSLE subjects. Also, indirect costs were not evaluated in this study.

Conclusion:

Subjects with lupus nephritis or NPSLE have high costs and resource use, compared to unaffected controls.     

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.