Key Points
Question
Among patients in the US diagnosed with Lyme disease (LD), what health care costs are associated with localized or disseminated disease?
Findings
In this cohort study involving 70 531 case patients with LD, direct health care costs of LD per patient were consistently high across all methods of estimation ($2227-$5571), particularly for those with disseminated disease.
Meaning
These findings suggest that health care costs associated with an LD diagnosis are high and represent a burden for patients and the health care system.
This cohort study assesses health care costs associated with Lyme disease, stratified by localized and disseminated disease, among patients in the US.
Abstract
Importance
Lyme disease (LD) is the most common vector-borne illness in the US. Given the increasing prevalence and expanding geographic bounds of LD, in-depth, up-to-date understanding of costs associated with an LD diagnosis, including patient out-of-pocket (OOP) costs, is needed.
Objective
To assess health care costs in a broad US population diagnosed with LD, overall and stratified by localized disease vs disseminated disease.
Design, Setting, and Participants
This retrospective cohort study identified patients from Optum’s deidentified Market Clarity Data (Optum Market Clarity) between December 2, 2014, and January 30, 2023 (study period), with an LD diagnosis between January 1, 2016, and December 31, 2022 (identification period), having at least 14 months of continuous health plan enrollment. Optum Market Clarity is an integrated, multisource medical claims, pharmacy claims, and electronic health records data set. Outpatients had a claim with an LD diagnosis plus relevant antibiotics within 30 days, and inpatients had a claim with LD as the primary diagnosis or as a secondary diagnosis with an LD-associated condition as the primary diagnosis. Data were analyzed from February 27, 2023, to October 20, 2025.
Exposure
The main exposure was LD diagnosis. Case patients were classified as having disseminated, localized, or indeterminate LD based on diagnosis codes for LD and LD-associated conditions, inpatient vs outpatient services, or antibiotic treatment type.
Main Outcomes and Measures
Health care costs (reported in US dollars) for LD cases overall and stratified by localized disease vs disseminated disease were assessed 4 ways: (1) LD-specific costs per episode, (2) all-cause 6-month baseline vs follow-up costs for case patients with LD, (3) all-cause 6-month follow-up costs for case patients with LD compared with the control group, and (4) multivariable case-control analysis. Costs are reported as estimated direct (standardized) costs and patient OOP costs. Wald 95% CIs were used for means of cost measures.
Results
A total of 70 531 case patients with LD were included. Their mean (SD) age was 44.8 (21.3) years; 51.3% were female. Estimated direct costs of LD were substantial across assessment methods, including episode cost (mean, $2227 [95% CI, $2111-$2342]), case patients as self-controls analysis (difference, $3304 [95% CI, $3117-$3491] in mean 6-month costs between baseline and follow-up), case-control analysis (difference, $4098 [95% CI, $3888-$4307] in mean 6-month follow-up costs), and multivariable-adjusted analysis (case-control difference, $5571 in projected mean 6-month follow-up costs; cost ratio, 1.96 [95% CI, 1.90-2.02]). OOP costs were available for 10 962 patients (15.5%) with LD. Mean OOP costs attributed to LD ranged from $188 to $399. Extrapolating to the US population in high-incidence states, annual costs of LD could range between $591 million and $1.05 billion (2022 dollars), with $411 to $771 million attributable to disseminated disease.
Conclusions and Relevance
In this retrospective cohort study, LD presented a large financial burden to the health care system and patients, especially for those with disseminated disease. These findings highlight the need for effective preventive measures to reduce costs for patients and the health care system.
Introduction
Lyme disease (LD) is the most common vector-borne illness in the US,1 with an estimated 476 000 cases diagnosed and treated each year.2 LD occurs focally in 15 high-incidence US states and Washington, DC3; the geographic distribution is expanding.2 Most commonly, patients have localized disease, which presents as a single-lesion erythema migrans, often accompanied by flulike symptoms.4 Patients with disseminated disease manifest symptoms including multiple erythema migrans rashes, joint pain and swelling, and specific neurologic or cardiac symptoms.5
Past studies have evaluated LD-related health care costs in the US. Zhang et al6 estimated direct medical costs for patients with LD identified from medical records, including those with early-stage or late-stage disease, during 1997 to 2000 for 5 counties in Maryland. Hook et al7 conducted a prospective cost-of-illness analysis to estimate direct medical costs during 2014 to 2016, including costs associated with localized and disseminated disease, for patients identified from surveillance efforts in 4 high-incidence states. Adrion et al8 assessed direct health care costs for patients younger than 65 years in a nationwide commercial health plan database during 2006 to 2010 but did not differentiate between costs of localized and disseminated disease.
There is a need to expand on the existing literature using more recent data that include a broad range of payers and patients of all ages and geographic regions that can differentiate costs for localized and disseminated disease and quantify costs borne by patients. The objective of this study was to assess health care costs (estimated direct and patient out-of-pocket [OOP] costs) in a broad US population diagnosed with LD, both overall and for patients with localized vs disseminated disease. The study examined costs for the US overall and stratified by state LD incidence level.
Methods
Study Overview
This retrospective cohort study identified patients from Optum’s deidentified Market Clarity Data (Optum Market Clarity) between December 2, 2014, and January 30, 2023 (study period), with an LD diagnosis between January 1, 2016, and December 31, 2022 (identification period), having at least 14 months of continuous health plan enrollment. Optum Market Clarity is an integrated, multisource medical claims, pharmacy claims, and electronic health records data set. Institutional review board approval or waiver of approval was not required because the study data were secondary and deidentified in accordance with US Department of Health and Human Services Privacy Rule requirements for deidentification codified at 45 CFR §164.514(b). This study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Study Population
Case Definition
An algorithm to identify outpatients with LD developed by the US Centers for Disease Control and Prevention (CDC),9,10 and later validated,11,12 was the basis of the current LD case definition. Outpatients had a nonhospitalization claim with an LD diagnosis, plus relevant antibiotics (eTable 1 in Supplement 1) within 30 days.9 Inpatients had an inpatient medical claim with LD as the primary diagnosis or as a secondary diagnosis with an LD-related condition as the primary diagnosis.10 All patients meeting the LD case definition were included in analyses, with additional criteria for continuous enrollment, matching, or both for some outcomes.
LD Classification
Case patients were classified as having disseminated or localized disease based on inpatient vs outpatient LD claims, LD diagnosis codes (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] A69.21-A69.29 vs A69.20), intravenous vs oral antibiotics (eTable 1 in Supplement 1), or diagnosis codes for manifestations of disseminated disease on or within 30 days of the index date.13 Case patients were classified as having indeterminate disease if they either had oral antibiotic treatment with at least a 29-day supply or had diagnosis codes for a manifestation of disseminated LD on or within 30 days of the index date as well as during a 6-month baseline period (212 to 31 days before the index date).
Study Variables
Patient age (all ages), sex, insurance type, and geography were collected from claims. State of residence was classified into US geographic region14 and LD incidence status, defined as (1) high incidence for LD as of 2021, (2) neighboring a high-incidence state, or (3) neither (eTable 2 in Supplement 1).15 Race and ethnicity were self-reported in electronic health record data as Asian, Black, White, or other or unknown race (ie, the assigned value in Optum Market Clarity for any reported race that could not be categorized as Asian, Black, or White, or when race was not reported) and as Hispanic, non-Hispanic, or unknown ethnicity. These data were collected because of previously observed differences in LD surveillance case counts, as well as severity of disease manifestations at the time of diagnosis, between patients with LD of other racial and ethnic groups and White patients in the US.16,17 Outcomes included 6-month all-cause health care costs (medical and pharmacy costs) and LD-specific health care costs (not including pharmacy costs). Costs were considered LD specific when an LD diagnosis code (ICD-10 A69.xx) was present on medical claims. Pharmacy costs were not included in LD-specific costs because pharmacy claims do not include diagnosis codes, and antibiotics used to treat LD may be used to treat non-LD conditions. To estimate direct health care costs, Optum applied proprietary normalized pricing algorithms to the claims data to create standardized prices that reflect the intensity of care provided where differences in price reflect differences in utilization. The standardized prices estimate health plan allowed payment amounts in US dollars, and they were inflation-adjusted to 2022 based on the Consumer Price Index health care component. Patient OOP costs represent actual amounts on claims that were patients’ responsibility (coinsurance, copay, or deductible). OOP costs were assessed for the subset of patients covered by health plans that provided claims to Optum Market Clarity with OOP amounts. This study did not compare OOP costs to the estimated direct costs because OOP costs were not standardized.
Statistical Analysis
Data were analyzed from February 27, 2023, to October 20, 2025. Costs included all-cause total, medical (ambulatory, emergency, inpatient, other medical [including outpatient laboratory]), and pharmacy costs and LD-specific medical costs. Means (95% CIs) and SDs, as well as medians and IQRs, were calculated. Wald 95% CIs were used for means of cost measures. Costs were analyzed for LD cases overall and stratified by localized disease vs disseminated disease, as well as by state LD incidence status, using the following 4 methods. First, for LD episode analysis, LD-specific medical costs were calculated for the duration of each patient’s episode with LD—from the index date through the date of the latest medical claim with an LD diagnosis followed by 12 months with no LD claims or through the end of the study period, whichever was sooner.
Second, in the case patients as self-controls analysis, all-cause health care costs were compared between the 6-month baseline period and a 6-month follow-up period (30 days before the index date through 151 days following the index date) among case patients enrolled during the full 6-month follow-up period. The 30 days before the index date were included during follow-up to capture costs possibly incurred during diagnostic workup before an LD diagnosis.
Third, individuals in the control group were matched 3:1 to case patients by a combination of hard matching and propensity score matching on demographic and clinical characteristics (eTables 3 and 4 in Supplement 1). Index dates of case patients were assigned to the matched control group. Eligible individuals in the control group for the match had at least 14 months of continuous enrollment. All-cause health care costs for the 6-month follow-up period were compared between case patients and the matched control group among those enrolled for the full 6-month follow-up period. The match was not retained when the full population was subset to those with 6-month continuous enrollment in follow-up, because attrition occurred without regard to case-control match status.
Fourth, multivariable-adjusted analysis controlled for any postmatch residual differences in patient characteristics (including comorbidity burden) and any imbalances between cohorts introduced when subsetting the population, as well as 6-month baseline all-cause total health care costs (quartiles). Generalized linear modeling with gamma distribution and log link compared 6-month follow-up all-cause health care costs between case patients and the control group overall and between LD classification subgroups and the control group to produce cost ratios. Model-based projected values of costs were also calculated. Two-part models were used for patient OOP costs because more than 10% of patients had zero-dollar costs for the outcome. The first model examined the odds of having a nonzero cost; the second examined the incremental cohort effect among patients with nonzero costs.
Finally, given that the LD case definition algorithm was validated in high-incidence states, exploratory analyses extrapolating this study’s results to estimate total health care costs of LD were limited to these states. The observed mean costs and distributions of case patients with localized, disseminated, and indeterminate disease for high-incidence states from the current study, estimated counts of case patients with LD in high-incidence states,2 and the positive predictive value for the LD case definition algorithm (confirmed and probable cases)12 were used to produce the total LD cost burden for high-incidence states.
All costs are reported in US dollars. Two-sided P < .05 was considered statistically significant. Analyses were conducted using SAS, version 9.4 (SAS Inc).
Results
Patient Population
This study included 70 531 case patients with LD (eFigure 1 in Supplement 1). A total of 51.3% of patients were female and 48.7% were male, with a mean (SD) age of 44.8 (21.3) years. In terms of race, 1.0% of case patients identified as Asian, 1.8% identified as Black, and 73.6% identified as White; race was categorized as other or unknown or was missing for 23.7%. In terms of ethnicity, 2.1% of case patients identified as Hispanic and 62.4% identified as non-Hispanic; ethnicity was unknown or missing for 35.6%. A total of 46 225 case patients (65.5%) were classified as having localized LD, 15 830 (22.4%) as having disseminated LD, and 8476 (12.0%) as having indeterminate LD (Table 1). More than three-quarters of patients (76.1%) lived in a state or district with high LD incidence, and 13.7% lived in states neighboring a high-incidence state or district. Patient demographics by state LD incidence status are provided in eTable 5 in Supplement 1.
Table 1. Demographic and Clinical Characteristics of Case Patients With LD in Optum Market Clarity, 2016-2022a.
| Characteristic | Case patients overall (N = 70 531) | LD classification subgroup | ||
|---|---|---|---|---|
| Localized (n = 46 225) | Disseminated (n = 15 830) | Indeterminate (n = 8476) | ||
| Age, mean (SD), y | 44.8 (21.3) | 43.9 (21.9) | 46.5 (20.8) | 46.8 (18.4) |
| Sex | ||||
| Female | 36 197 (51.3) | 23 313 (50.4) | 7997 (50.5) | 4887 (57.7) |
| Male | 34 334 (48.7) | 22 912 (49.6) | 7833 (49.5) | 3589 (42.3) |
| Raceb | ||||
| Asian | 679 (1.0) | 443 (1.0) | 159 (1.0) | 77 (0.9) |
| Black | 1253 (1.8) | 645 (1.4) | 452 (2.9) | 156 (1.8) |
| White | 51 914 (73.6) | 34 171 (73.9) | 11 443 (72.3) | 6300 (74.3) |
| Other or unknown racec or missing | 16 685 (23.7) | 10 966 (23.7) | 3776 (23.9) | 1943 (22.9) |
| Ethnicityb | ||||
| Hispanic | 1455 (2.1) | 891 (1.9) | 402 (2.5) | 162 (1.9) |
| Non-Hispanic | 43 992 (62.4) | 28 811 (62.3) | 9849 (62.2) | 5332 (62.9) |
| Unknown or missing | 25 084 (35.6) | 16 523 (35.7) | 5579 (35.2) | 2982 (35.2) |
| State LD incidence status | ||||
| High-incidence state or districtd | 53 703 (76.1) | 35 946 (77.8) | 11 680 (73.8) | 6077 (71.7) |
| Neighboring a high-incidence state or districte | 9640 (13.7) | 6142 (13.3) | 2292 (14.5) | 1206 (14.2) |
| Non–high-incidence, non-neighboring | 7188 (10.2) | 4137 (8.9) | 1858 (11.7) | 1193 (14.1) |
| US Census region | ||||
| Northeast | 47 312 (67.1) | 31 531 (68.2) | 10 325 (65.2) | 5456 (64.4) |
| Midwest | 14 542 (20.6) | 9695 (21.0) | 3239 (20.5) | 1608 (19.0) |
| South | 6581 (9.3) | 3813 (8.2) | 1792 (11.3) | 976 (11.5) |
| West | 2096 (3.0) | 1186 (2.6) | 474 (3.0) | 436 (5.1) |
| Insurance type | ||||
| Commercial only | 49 276 (69.9) | 32 518 (70.3) | 10 535 (66.6) | 6223 (73.4) |
| Medicare only | 8709 (12.4) | 5551 (12.0) | 2197 (13.9) | 961 (11.3) |
| Medicaid | 7084 (10.0) | 4669 (10.1) | 1793 (11.3) | 622 (7.3) |
| Multiple of these | 2113 (3.0) | 1270 (2.8) | 574 (3.6) | 269 (3.2) |
| Other (none of these) | 3349 (4.7) | 2217 (4.8) | 731 (4.6) | 401 (4.7) |
| Baseline Quan-Charlson Comorbidity score, mean (SD) | 0.51 (1.12) | 0.44 (1.03) | 0.64 (1.29) | 0.61 (1.20) |
Abbreviation: LD, Lyme disease.
Unless otherwise indicated, values are presented as No. (%) of patients. Percentages may not sum to 100% due to rounding.
Race and ethnicity variables in Optum Market Clarity are sourced from a patient’s electronic health record and are self-reported by the patient.
Assigned in Optum Market Clarity for any reported race that could not be categorized as Asian, Black, or White or when race was not reported.
Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Washington, DC, West Virginia, and Wisconsin.
Illinois, Indiana, Iowa, Kentucky, Michigan, North Carolina, North Dakota, Ohio, South Dakota, and Tennessee.
LD Episode Analysis
All 70 531 case patients were included in the LD episode analysis; 10 962 case patients (15.5%) had OOP cost data available (eFigure 1 in Supplement 1). Mean LD-specific direct medical costs per episode were $2227 (95% CI, $2111-$2342) for case patients overall, $6833 (95% CI, $6397-$7269) for those with disseminated disease, and $695 (95% CI, $628-$762) for those with localized disease (Table 2). Total LD-specific direct health care costs for case patients with disseminated disease accounted for 68.9% of the total LD-specific direct health care costs for all case patients in the episode-level analysis. For case patients in high-incidence states (n = 53 703), mean LD-specific direct medical costs per episode were $2002 (95% CI, $1878-$2126) for case patients overall, $6400 (95% CI, $5919-$6880) for those with disseminated disease, and $638 (95% CI, $573-$702) for those with localized disease. Mean LD-specific patient OOP medical costs were $188 (95% CI, $177-$200) for case patients overall, $401 (95% CI, $362-$441) for those with disseminated disease, and $107 (95% CI, $98-$116) for those with localized disease. For case patients with OOP cost data in high-incidence states (n = 8808), mean LD-specific patient OOP medical costs were $173 (95% CI, $162-$184) for case patients overall, $380 (95% CI, $340-$421) for those with disseminated disease, and $101 (95% CI, $93-$109) for those with localized disease. eTable 6 in Supplement 1 presents results for neighboring and non-neighboring states.
Table 2. LD-Specific Direct and Patient OOP Total Medical Costs per Episode (LD Episode Analysis).
| Characteristic | No. of case patients | LD-specific total medical costs per episode, $ | |
|---|---|---|---|
| Mean (95% CI) [SD]a | Median (IQR) | ||
| Direct costs b , c | |||
| All states | |||
| Case patients overall | 70 531 | 2227 (2111-2342) [15 690] | 229 (129-545) |
| LD classification subgroup | |||
| Localized | 46 225 | 695 (628-762) [7348] | 177 (100-367) |
| Disseminated | 15 830 | 6833 (6397-7269) [27 983] | 431 (164-2105) |
| Indeterminate | 8476 | 1975 (1646-2304) [15 466] | 339 (151-854) |
| High-incidence statesd | |||
| Case patients overall | 53 703 | 2002 (1878-2126) [14 655] | 217 (122-502) |
| LD classification subgroup | |||
| Localized | 35 946 | 638 (573-702) [6221] | 174 (96-351) |
| Disseminated | 11 680 | 6400 (5919-6880) [26 486] | 403 (156-1980) |
| Indeterminate | 6077 | 1619 (1204-2034) [16 502] | 307 (151-727) |
| OOP costs b , e | |||
| All states | |||
| Case patients overall | 10 962 | 188 (177-200) [628] | 30 (10-106) |
| LD classification subgroup | |||
| Localized | 7258 | 107 (98-116) [397] | 30 (10-78) |
| Disseminated | 2373 | 401 (362-441) [992] | 50 (10-252) |
| Indeterminate | 1331 | 253 (214-291) [716] | 43 (7-182) |
| High-incidence statesd | |||
| Case patients overall | 8808 | 173 (162-184) [535] | 30 (10-100) |
| LD classification subgroup | |||
| Localized | 5982 | 101 (93-109) [322] | 30 (10-75) |
| Disseminated | 1842 | 380 (340-421) [894] | 50 (13-253) |
| Indeterminate | 984 | 222 (186-257) [567] | 40 (10-150) |
Abbreviations: ICD-10, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; LD, Lyme disease; OOP, out-of-pocket.
Wald 95% CIs were used for means of cost measures. Some SDs are very large due to extreme values, which are not unexpected with health care claims data.
From medical claims with an ICD-10 LD diagnosis code (A69.xx).
Standardized 2022 Consumer Price Index–adjusted costs for ambulatory, emergency, inpatient, and other medical services; does not include pharmacy costs.
Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Washington, DC, West Virginia, and Wisconsin.
OOP costs (coinsurance, copay, deductible) for ambulatory, emergency, inpatient, and other medical services; does not include pharmacy costs. OOP costs provided for the subset of patients covered by health plans that contributed OOP data to Optum Market Clarity.
Case Patients as Self-Controls Analysis
Case patients with continuous enrollment during the 6-month follow-up period (n = 64 893) were included in the case patients as self-controls analysis. The OOP analysis included 9908 case patients (eFigure 1 in Supplement 1). For the 64 893 case patients overall, mean all-cause total direct health care costs were $3304 (95% CI, $3117-$3491) greater for the 6-month follow-up period than the 6-month baseline period (disseminated disease: $10 130 [95% CI, $9531-$10 728] greater; localized disease: $1381 [95% CI, $1207-$1554] greater) (Table 3). For case patients overall in high-incidence states (n = 49 469), mean all-cause total direct health care costs were $3217 (95% CI, $3017-$3417) greater for the 6-month follow-up period than the 6-month baseline period (disseminated disease: $10 020 [95% CI, $9355-$10 686] greater; localized disease: $1340 [95% CI, $1161-$1519] greater). Among case patients overall with OOP cost data (n = 9908), mean OOP costs were $240 (95% CI, $210-$271) greater at follow-up than at baseline (disseminated disease: $643 [95% CI, $561-$725] greater; localized disease: $123 [95% CI, $91-$154] greater). Among case patients overall with OOP cost data in high-incidence states (n = 7982), mean costs were $236 (95% CI, $204-$269) greater at follow-up than at baseline (disseminated disease: $623 [95% CI, $533-$713] greater; localized disease: $121 [95% CI, $88-$154] greater). eTable 7 in Supplement 1 describes results for neighboring and non-neighboring states.
Table 3. All-Cause Direct and Patient OOP Total Health Care Costs, 6-Month Baseline vs Follow-Up (Case Patients as Self-Controls Analysis).
| Study groupa | No. of case patients | All-cause total health care costs, $ | Difference in means (95% CI), $d | P valuee | |||
|---|---|---|---|---|---|---|---|
| Baseline, 6 mob | Follow-up, 6 moc | ||||||
| Mean (95% CI) [SD] | Median (IQR) | Mean (95% CI) [SD] | Median (IQR) | ||||
| Direct costsf | |||||||
| All states | |||||||
| Case patients overall | 64 893 | 6714 (6567-6861) [19 119] | 1832 (511-5685) | 10 018 (9827-10 209) [24 839] | 3298 (1234-8836) | 3304 (3117-3491) | <.001 |
| LD classification subgroup | |||||||
| Localized | 42 650 | 5359 (5199-5518) [16 790] | 1439 (407-4483) | 6739 (6573-6905) [17 488] | 2327 (925-6022) | 1381 (1207-1554) | <.001 |
| Disseminated | 14 455 | 8769 (8421-9117) [21 339] | 2422 (651-7562) | 18 898 (18 270-19 527) [38 553] | 7036 (2722-19 623) | 10 130 (9531-10 728) | <.001 |
| Indeterminate | 7788 | 10 324 (9768-10 880) [25 020] | 3860 (1357-9967) | 11 490 (10 994-11 987) [22 363] | 5189 (2239-11 886) | 1166 (682-1650) | <.001 |
| High-incidence statesg | |||||||
| Case patients overall | 49 469 | 6175 (6031-6319) [16 328] | 1701 (484-5201) | 9392 (9184-9600) [23 577] | 3101 (1175-8105) | 3217 (3017-3417) | <.001 |
| LD classification subgroup | |||||||
| Localized | 33 186 | 5101 (4958-5245) [13 293] | 1395 (402-4269) | 6442 (6257-6626) [17 129] | 2268 (911-5746) | 1340 (1161-1519) | <.001 |
| Disseminated | 10 709 | 7861 (7489-8232) [19 600] | 2127 (588-6629) | 17 881 (17 185-18 577) [36 752] | 6435 (2533-18 328) | 10 020 (9355-10 686) | <.001 |
| Indeterminate | 5574 | 9328 (8710-9946) [23 531] | 3350 (1168-8675) | 10 647 (10 122-11 172) [19 998] | 4765 (1986-10 889) | 1320 (779-1860) | <.001 |
| OOP costsh | |||||||
| All states | |||||||
| Case patients overall | 9908 | 767 (743-790) [1191] | 336 (85-926) | 1007 (981-1034) [1353] | 526 (211-1231) | 240 (210-271) | <.001 |
| LD classification subgroup | |||||||
| Localized | 6579 | 654 (628-679) [1052] | 279 (60-765) | 777 (751-802) [1067] | 395 (166-935) | 123 (91-154) | <.001 |
| Disseminated | 2123 | 903 (847-958) [1309] | 412 (116-1110) | 1546 (1472-1620) [1736] | 959 (414-2093) | 643 (561-725) | <.001 |
| Indeterminate | 1206 | 1144 (1057-1231) [1538] | 590 (224-1431) | 1316 (1225-1408) [1625] | 830 (360-1665) | 173 (61-285) | .003 |
| High-incidence statesg | |||||||
| Case patients overall | 7982 | 733 (707-758) [1148] | 320 (82-880) | 969 (941-997) [1291] | 505 (206-1191) | 236 (204-269) | <.001 |
| LD classification subgroup | |||||||
| Localized | 5431 | 641 (614-668) [1015] | 280 (62-752) | 762 (734-790) [1050] | 390 (169-917) | 121 (88-154) | <.001 |
| Disseminated | 1658 | 873 (810-936) [1306] | 374 (106-1072) | 1496 (1415-1577) [1678] | 932 (403-2050) | 623 (533-713) | <.001 |
| Indeterminate | 893 | 1031 (934-1128) [1476] | 518 (188-1240) | 1251 (1155-1347) [1458] | 773 (319-1589) | 220 (99-341) | <.001 |
Abbreviations: LD, Lyme disease; OOP, out-of-pocket.
Analysis restricted to individuals with continuous enrollment during 6-month follow-up period.
Baseline period (6 months): index date minus 212 days through index date minus 31 days. Some SDs are very large due to extreme values, which are not unexpected with health care claims data.
Follow-up period (6 months): index date minus 30 days through index date plus 151 days. Some SDs are very large due to extreme values, which are not unexpected with health care claims data.
Wald 95% CIs were used for difference in means of cost measures.
Paired t test was used for cost measures.
Standardized 2022 Consumer Price Index–adjusted costs for ambulatory, emergency, inpatient, other medical services, and pharmacy costs.
Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Washington, DC, West Virginia, and Wisconsin.
OOP costs (coinsurance, copay, deductible) for ambulatory, emergency, inpatient, other medical services, and pharmacy costs. OOP costs provided for the subset of patients covered by health plans that contributed OOP data to Optum Market Clarity.
Case-Control Analysis
For the case-control analysis, case patients with LD (n = 70 529) were matched to the control group (n = 211 587), with 2 unmatched case patients excluded (eTables 3 and 4 in Supplement 1). The continuous enrollment requirement for the 6-month follow-up period resulted in 64 891 case patients and 168 509 individuals in the control group (eFigure 1 in Supplement 1). For the patient OOP analysis, 9908 case patients and 29 156 individuals in the control group were included. Mean all-cause total direct health care costs in the 6-month follow-up period were $4098 (95% CI, $3888-$4307) greater for case patients overall than for the control group (disseminated disease: $12 978 [95% CI, $12 346-$13 610] greater; localized disease: $819 [95% CI, $629-$1009] greater) (Table 4). Among those in high-incidence states (n = 49 467), mean all-cause total direct health care costs in the 6-month follow-up period were $3569 (95% CI, $3338-$3799) greater for case patients overall than for the control group (disseminated disease: $12 057 [95% CI, $11 357-$12 758] greater; localized disease: $618 [95% CI, $404-$832] greater). For patient OOP costs, mean total 6-month follow-up costs were $390 (95% CI, $360-419) greater for case patients overall than for the control group (disseminated disease: $928 [95% CI, $854-$1003] greater; localized disease: $159 [95% CI, $130-$188] greater). Among those with OOP costs in high-incidence states (n = 7982), mean total 6-month follow-up costs were $367 (95% CI, $335-$399) greater for case patients overall than for the control group (disseminated disease: $894 [95% CI, $811-$976] greater; localized disease: $160 [95% CI, $128-$191] greater). For both direct and OOP total health care costs, mean costs were greater for case patients overall and for each LD subgroup than for the control group for every cost category, except inpatient costs for case patients with localized and indeterminate disease (eFigure 2 in Supplement 1). eTable 8 in Supplement 1 describes results for neighboring and non-neighboring states.
Table 4. Mean All-Cause Direct and Patient OOP Total Health Care Costs (Unadjusted Case-Control Analysis).
| Study groupa | No. of case patients or individuals in the control group | All-cause total health care costs, $ | Difference in means, case patients vs control group (95% CI)c | P valued | |
|---|---|---|---|---|---|
| Follow-up 6 mo, mean (95% CI) [SD]b | Follow-up 6 mo, median (IQR)b | ||||
| Direct costse | |||||
| All states | |||||
| Case patients overall | 64 891 | 10 018 (9827-10 209) [24 839] | 3298 (1233-8836) | 4098 (3888-4307) | <.001 |
| LD classification subgroup | |||||
| Localized | 42 649 | 6739 (6573-6905) [17 488] | 2327 (925-6022) | 819 (629-1009) | <.001 |
| Disseminated | 14 455 | 18 898 (18 270-19 527) [38 553] | 7036 (2722-19 623) | 12 978 (12 346-13 610) | <.001 |
| Indeterminate | 7787 | 11 492 (10 995-11 988) [22 364] | 5189 (2239-11 888) | 5571 (5067-6076) | <.001 |
| Control groupf | 168 509 | 5920 (5823-6018) [20 473] | 1135 (264-4039) | NA | NA |
| High-incidence statesg | |||||
| Case patients overall | 49 467 | 9392 (9184-9600) [23 577] | 3101 (1175-8105) | 3569 (3338-3799) | <.001 |
| LD classification subgroup | |||||
| Localized | 33 185 | 6442 (6258-6626) [17 129] | 2268 (911-5746) | 618 (404-832) | <.001 |
| Disseminated | 10 709 | 17 881 (17 185-18 577) [36 752] | 6435 (2533-18 328) | 12 057 (11 357-12 758) | <.001 |
| Indeterminate | 5573 | 10 649 (10 123-11 174) [19 999] | 4767 (1986-10 889) | 4825 (4290-5360) | <.001 |
| Control groupf | 128 562 | 5824 (5711-5937) [20 656] | 1144 (275-3985) | NA | NA |
| OOP costsh | |||||
| All states | |||||
| Case patients overall | 9908 | 1007 (981-1034) [1353] | 526 (211-1231) | 390 (360-419) | <.001 |
| LD classification subgroup | |||||
| Localized | 6579 | 777 (751-802) [1067] | 395 (166-935) | 159 (130-188) | <.001 |
| Disseminated | 2123 | 1546 (1472-1620) [1736] | 959 (414-2093) | 928 (854-1003) | <.001 |
| Indeterminate | 1206 | 1316 (1225-1408) [1625] | 830 (360-1665) | 699 (606-792) | <.001 |
| Control groupf | 29 156 | 617 (604-631) [1139] | 235 (50-698) | NA | NA |
| High-incidence statesg | |||||
| Case patients overall | 7982 | 969 (941-997) [1291] | 505 (206-1191) | 367 (335-399) | <.001 |
| LD classification subgroup | |||||
| Localized | 5431 | 762 (734-790) [1050] | 390 (169-917) | 160 (128-191) | <.001 |
| Disseminated | 1658 | 1496 (1415-1577) [1678] | 932 (403-2050) | 894 (811-976) | <.001 |
| Indeterminate | 893 | 1251 (1155-1347) [1458] | 773 (319-1589) | 649 (552-746) | <.001 |
| Control groupf | 21 156 | 602 (587-617) [1125] | 235 (50-685) | NA | NA |
Abbreviations: LD, Lyme disease; NA, not applicable; OOP, out-of-pocket.
Analysis restricted to individuals with continuous enrollment during the 6-month follow-up period.
Follow-up period (6 months): index date minus 30 days through index date plus 151 days. Some SDs are very large due to extreme values, which are not unexpected with health care claims data.
Wald 95% CIs were used for difference in means of cost measures.
Z test using robust standard errors in an ordinary least-squares regression was used for cost measures.
Standardized 2022 Consumer Price Index–adjusted costs for ambulatory, emergency, inpatient, and other medical services and pharmacy costs.
The original 3:1 match of individuals in the control group to case patients overall was not retained in the 6-month follow-up period, because attrition of individuals with insufficient health plan enrollment occurred without regard to case-control match status.
Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Washington, DC, West Virginia, and Wisconsin.
OOP costs (coinsurance, copay, deductible) for ambulatory, emergency, inpatient, other medical services, and pharmacy costs. OOP costs provided for the subset of patients covered by health plans that contributed OOP data to Optum Market Clarity.
Multivariable Analysis
After adjustment for demographics, baseline comorbidity burden, and baseline health care costs, 6-month follow-up projected mean all-cause total direct health care costs were $5571 greater (cost ratio, 1.96 [95% CI, 1.90-2.02]) for case patients overall compared with the control group (disseminated disease: $15 834 greater; cost ratio, 3.73 [95% CI, 3.53-3.95]; localized disease: $2376 greater; cost ratio, 1.41 [95% CI, 1.36-1.46]) (Table 5). Among those in high-incidence states, 6-month projected mean all-cause total direct health care costs were $5089 greater (cost ratio, 1.89 [95% CI, 1.83-1.96]) for case patients overall compared with the control group (disseminated disease: $15 036 greater; cost ratio, 3.64 [95% CI, 3.41-3.90]; localized disease: $2107 greater; cost ratio, 1.37 [95% CI, 1.32-1.43]). For those with OOP cost data, 6-month projected mean OOP costs were $399 greater (cost ratio, 1.46 [95% CI, 1.41-1.51]) for case patients overall vs the control group (disseminated disease: $942 greater; cost ratio, 2.25 [95% CI, 2.10-2.41]; localized disease: $196 greater; cost ratio; 1.17 [95% CI, 1.12-1.22]) (OOP cost ratios are from nonzero values in the 2-part model; eTable 9 in Supplement 1). Among those with OOP cost data in high-incidence states, 6-month projected mean OOP costs were $378 greater (cost ratio, 1.45 [95% CI, 1.39-1.51]) for case patients overall vs the control group (disseminated disease: $928 greater; cost ratio, 2.27 [95% CI, 2.10-2.45]; localized disease: $184 greater for localized disease; cost ratio, 1.16 [95% CI, 1.11-1.21]). eTables 10 and 11 in Supplement 1 describes results for neighboring and non-neighboring states.
Table 5. Projected Mean All-Cause Direct Total Health Care Costs, 6-Month Follow-Up (Adjusted Case-Control Analysis)a.
| Study group | All-cause direct total health care costs (6 mo follow-up), $b | Cost ratio (95% CI)c | P valuec | |
|---|---|---|---|---|
| Projected mean cost | Difference vs control group | |||
| All states | ||||
| All case patients vs control group | ||||
| Case patients overall | 11 377 | 5571 | 1.96 (1.90-2.02) | <.001 |
| Control groupd | 5807 | Reference | 1 [Reference] | NA |
| LD subgroups vs control group | ||||
| LD classification subgroup | ||||
| Localized | 8175 | 2376 | 1.41 (1.36-1.46) | <.001 |
| Disseminated | 21 633 | 15 834 | 3.73 (3.53-3.95) | <.001 |
| Indeterminate | 9812 | 4013 | 1.69 (1.57-1.83) | <.001 |
| Control groupd | 5799 | Reference | 1 [Reference] | NA |
| High-incidence statese | ||||
| All case patients vs control group | ||||
| Case patients overall | 10 787 | 5089 | 1.89 (1.83-1.96) | <.001 |
| Control groupd | 5697 | Reference | 1 [Reference] | NA |
| LD subgroups vs control group | ||||
| LD classification subgroup | ||||
| Localized | 7796 | 2107 | 1.37 (1.32-1.43) | <.001 |
| Disseminated | 20 725 | 15 036 | 3.64 (3.41-3.90) | <.001 |
| Indeterminate | 9409 | 3720 | 1.65 (1.51-1.81) | <.001 |
| Control groupd | 5689 | Reference | 1 [Reference] | NA |
Abbreviations: LD, Lyme disease; NA, not applicable; OOP, out-of-pocket.
Analysis restricted to individuals with continuous enrollment during 6-month follow-up period. Adjusted for 6-month baseline cost quartiles, 5-year age group, sex, race, ethnicity, LD incidence status of state of residence, insurance type, and baseline 12-month Quan-Charlson Comorbidity Index score.
Standardized 2022 Consumer Price Index–adjusted costs for ambulatory, emergency, inpatient, and other medical services and pharmacy costs. Follow-up period (6 months): index date minus 30 days through index date plus 151 days.
Cost ratio and P values from generalized linear model with gamma distribution.
For all analyses, the original 3:1 match of individuals in the control group to patients with LD was not retained in the 6-month follow-up period, because attrition of individuals with insufficient health plan enrollment occurred without regard to case-control match status.
Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Washington, DC, West Virginia, and Wisconsin.
Extrapolation to High-Incidence States
LD episode and case-control results, as lower and upper estimates, were extrapolated to the expected annual number of case patients with LD in high-incidence states. The results suggested that total LD health care costs could range from $591 million to $1.05 billion (2022 dollars), with $411 to $771 million attributable to disseminated disease (eTable 12 in Supplement 1).
Discussion
This study expands on existing literature by using a large, multisource claims dataset to conduct multiple analyses of health care costs stratified by LD classification and state LD incidence status. Direct health care costs of LD were substantial across methods, including mean episode cost ($2227), case patients as self-controls analysis (difference of $3304 in mean 6-month baseline and follow-up costs), and case-control analysis (difference of $4098 in mean 6-month follow-up costs). Costs were lowest in the episode-level analysis because calculations were based on variable time periods and excluded pharmacy costs. The multivariable-adjusted analysis, accounting for patients’ baseline characteristics, produced the highest cost estimates (case-control difference of $5571 in projected mean total all-cause 6-month costs). Similar results were found for high-incidence states.
Across analyses, case patients with disseminated disease had higher total health care costs attributed to LD than those with localized disease. Although 22.4% of case patients were classified as having disseminated disease, they accounted for 68.9% of total LD-specific direct health care costs in the episode-level analysis.
The results of this study generally align with previous studies reporting a large economic burden posed by LD and greater direct medical costs incurred by patients with disseminated vs localized disease.6,7,8 Zhang et al6 found mean direct medical costs of $464 and $1380 ($972 and $2892 in 2022 dollars), respectively, for patients diagnosed with early-stage and late-stage LD in 2000. Hook et al7 found that for 2014 to 2016, mean total direct medical costs per patient with LD were $1333 ($1571 in 2022 dollars), with costs of $668 and $2537 ($787 and $2990 in 2022 dollars), respectively, for patients with localized and disseminated LD. Our current estimates of LD-specific direct medical costs per LD episode ($2227 overall, $695 localized, and $6833 disseminated [2022 dollars]) may be higher than previous studies, especially for disseminated LD, because this study allowed LD episodes to extend longer than 1 year. Also, our study used standardized prices to estimate insurance allowed amounts; in contrast, Zhang et al6 used practitioner charges for LD diagnosis and treatment, and Hook7 calculated costs from patient-reported utilization (verified with medical records) and assigned average costs from external sources.
Hook et al7 reported mean patient-paid direct medical costs of $314 and $628 ($370 and $740 in 2022 dollars) for patients with localized and disseminated LD, respectively. The estimated LD-specific patient OOP medical costs per LD episode in our study ($107 localized and $401 disseminated [2022 dollars]) may be lower than those of Hook et al due to our use of an insured population, our exclusion of pharmacy costs, and differences in cost estimation methods.
Using multivariable analysis, Adrion et al8 reported that patients with LD incurred $2968 ($4455 in 2022 dollars) higher estimated mean 12-month total health care costs than the control group. Multivariable analysis in the current study using a 6-month period found $5571 higher projected mean total health care costs. Although both studies estimated insurance allowed amounts, costs reported by Adrion et al were based on commercially insured patients only; the present study used standardized costs for patients covered by a variety of insurance types. The current study included all age groups; Adrion et al restricted ages to younger than 65 years. The studies used different time periods, further challenging comparisons.
Strengths of our study include the use of a large, nationwide dataset with patients of all ages, covered by a variety of insurance types. It incorporated multiple analyses to corroborate estimates of LD costs and utilized an existing, validated algorithm to identify case patients with LD. Stratification by state LD incidence status provided estimates consistent with the high-incidence population used to validate the LD case definition algorithm.11 The case patients as self-controls analysis had not been used in previous studies and accounted for intraperson characteristics associated with LD exposure and risk (eg, outdoor activities) that could not be fully accounted for in the case-control multivariable analysis.
Limitations
This study has some limitations. The claims-based algorithm to classify case patients with LD as having localized or disseminated disease has not been validated, so misclassification may have occurred; however, it was based on a CDC case-identification algorithm that has been validated.11 This study included an indeterminate category to mitigate misclassification. The 6-month follow-up period may have been too short to capture the costs for patients with persistent symptoms. The cut point between baseline and follow-up periods of 30 days before the index date may not have been sufficiently nuanced to address differences in the diagnostic process for case patients with localized and disseminated disease but has been used in previous research.7 The CDC LD case-identification algorithm was optimized in 202418; however, at the time of this study, we used the most current version available.11 This study included insured US patients in Optum Market Clarity and may not be generalizable to all patients with LD. OOP costs were only available for a subset of patients.
Conclusions
As the findings of this retrospective cohort study suggest, LD presents a large financial burden to the health care system and a nontrivial burden to patients, especially those with disseminated disease. Extrapolating this study’s results, the annual health care costs of LD in high-incidence states could range between $591 million and $1.05 billion (2022 dollars). This estimation does not include all states or indirect costs. Given the continued geographic expansion of LD, it is expected that costs will increase. Thus, there is a need for effective preventive measures to reduce costs for patients and the health care system.
eTable 1. Antibiotic Medications Used for Lyme Disease (LD) Treatment and for Study LD Case Identification, Generic Name, and Mode of Administration
eTable 2. Lyme Disease (LD) High-Incidence and Neighboring States and Districts
eTable 3. Prematch and Postmatch Differences in Matching Variables, Lyme Disease (LD) Cases vs Controls (Hard Matching Variables)
eTable 4. Prematch and Postmatch Differences in Matching Variables, Lyme Disease (LD) Cases vs Controls (Propensity Score Matching Variables)
eFigure 1. Study Population Selection
eFigure 2. Unadjusted Mean All-Cause Direct and Patient Out-of-Pocket (OOP) Health Care Costs by Cost Categories, 6-Month Follow-Up
eTable 5. Demographic and Clinical Characteristics of Individuals Identified as Lyme Disease (LD) Cases in Optum Market Clarity, 2016-2022, Stratified by State LD Incidence Status
eTable 6. Lyme Disease (LD)–Specific Direct and Patient Out-of-Pocket (OOP) Total Medical Costs Per LD Episode, Neighboring and Non-Neighboring/Non-High-Incidence States (LD Episode Analysis)
eTable 7. All-Cause Direct and Patient Out-of-Pocket (OOP) Total Health Care Costs, 6-Month Baseline vs Follow-Up, Neighboring and Non-Neighboring/Non-High-Incidence States (Cases as Self-Controls Analysis)
eTable 8. Mean All-Cause Direct and Patient Out-of-Pocket (OOP) Total Health Care Costs, 6-Month Follow-Up; Neighboring and Non-Neighboring/Non-High-Incidence States (Unadjusted Case-Control Analysis)
eTable 9. Projected Mean All-Cause Patient Out-of-Pocket (OOP) Total Health Care Costs, 6-Month Follow-Up; All States and High-Incidence States (Adjusted Case-Control Analysis)
eTable 10. Projected Mean All-Cause Direct Total Health Care Costs, 6-Month Follow-Up; Neighboring and Non-Neighboring/Non-High-Incidence States (Adjusted Case-Control Analysis)
eTable 11. Projected Mean All-Cause Patient Out-of-Pocket (OOP) Total Health Care Costs, 6-Month Follow-Up; Neighboring and Non-Neighboring/Non-High-Incidence States (Adjusted Case-Control Analysis)
eTable 12. Extrapolation of Lyme Disease (LD)–Associated Health Care Costs to All Cases in High-Incidence States
Data Sharing Statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable 1. Antibiotic Medications Used for Lyme Disease (LD) Treatment and for Study LD Case Identification, Generic Name, and Mode of Administration
eTable 2. Lyme Disease (LD) High-Incidence and Neighboring States and Districts
eTable 3. Prematch and Postmatch Differences in Matching Variables, Lyme Disease (LD) Cases vs Controls (Hard Matching Variables)
eTable 4. Prematch and Postmatch Differences in Matching Variables, Lyme Disease (LD) Cases vs Controls (Propensity Score Matching Variables)
eFigure 1. Study Population Selection
eFigure 2. Unadjusted Mean All-Cause Direct and Patient Out-of-Pocket (OOP) Health Care Costs by Cost Categories, 6-Month Follow-Up
eTable 5. Demographic and Clinical Characteristics of Individuals Identified as Lyme Disease (LD) Cases in Optum Market Clarity, 2016-2022, Stratified by State LD Incidence Status
eTable 6. Lyme Disease (LD)–Specific Direct and Patient Out-of-Pocket (OOP) Total Medical Costs Per LD Episode, Neighboring and Non-Neighboring/Non-High-Incidence States (LD Episode Analysis)
eTable 7. All-Cause Direct and Patient Out-of-Pocket (OOP) Total Health Care Costs, 6-Month Baseline vs Follow-Up, Neighboring and Non-Neighboring/Non-High-Incidence States (Cases as Self-Controls Analysis)
eTable 8. Mean All-Cause Direct and Patient Out-of-Pocket (OOP) Total Health Care Costs, 6-Month Follow-Up; Neighboring and Non-Neighboring/Non-High-Incidence States (Unadjusted Case-Control Analysis)
eTable 9. Projected Mean All-Cause Patient Out-of-Pocket (OOP) Total Health Care Costs, 6-Month Follow-Up; All States and High-Incidence States (Adjusted Case-Control Analysis)
eTable 10. Projected Mean All-Cause Direct Total Health Care Costs, 6-Month Follow-Up; Neighboring and Non-Neighboring/Non-High-Incidence States (Adjusted Case-Control Analysis)
eTable 11. Projected Mean All-Cause Patient Out-of-Pocket (OOP) Total Health Care Costs, 6-Month Follow-Up; Neighboring and Non-Neighboring/Non-High-Incidence States (Adjusted Case-Control Analysis)
eTable 12. Extrapolation of Lyme Disease (LD)–Associated Health Care Costs to All Cases in High-Incidence States
Data Sharing Statement
