Abstract
Introduction
Lack of or delayed treatment of primary biliary cholangitis (PBC) is associated with worsening outcomes. This study assessed the real-world healthcare resource use (HRU) and costs of PBC in the USA to understand its economic burden by line of therapy.
Methods
This retrospective study analyzed IQVIA PharMetrics® Plus claims data (2016–2022) for three non-mutually exclusive cohorts of adults diagnosed with PBC from January 1, 2017: untreated; first-line (1L) treatment with ursodeoxycholic acid (UDCA); second-line or more (2L+) treatment after UDCA. Index date for each cohort was: untreated, date of PBC diagnosis; 1L, 1L treatment initiation; 2L+, 2L treatment initiation. All-cause per-patient per-year (PPPY) HRU and costs during baseline and follow-up periods were compared among groups.
Results
Patients in the untreated cohort had higher mean inpatient (IP) admissions (PPPY; 0.93 visits) and longer mean IP length of stay (LOS) (PPPY; 7.45 days) than the 1L (0.16 visits; 1.12 days) and 2L+ (0.19 visits; 1.77 days) cohorts during follow-up. Patients in the untreated cohort had the highest mean IP costs during the follow-up period (untreated: $37,974; 1L: $5854; 2L+: $6898). Compared with baseline, significantly higher HRU during follow-up was observed for the 1L and 2L+ cohorts regarding mean number of outpatient visits (incidence rate ratio [IRR]: 1.07; p = 0.001) and mean IP LOS (IRR: 2.12; p = 0.001), respectively.
Conclusions
These results highlight the importance of initiating timely treatment for PBC to reduce HRU and medical costs. The findings also demonstrate the need for novel, more effective PBC treatments.
Keywords: Economic burden, Primary biliary cholangitis, Rare disease, Real-world data
Plain Language Summary
Primary biliary cholangitis is a rare liver disease that gradually worsens over time and can be potentially life-threatening. Treatments are available for primary biliary cholangitis, but they do not work for everyone, and some people experience unpleasant side effects. Therefore, patients may need to try different treatments to determine what works best for them. This study looked at health insurance claims to understand how patients with primary biliary cholangitis use healthcare services and how much these services cost. The study focused on three groups of patients: those who did not receive any treatment for primary biliary cholangitis (untreated group), those who were treated with a medication called ursodeoxycholic acid as their first treatment (first-line group), and those who received additional treatments for primary biliary cholangitis after receiving ursodeoxycholic acid (second-line or more group). The results showed that after diagnosis, untreated patients were admitted to the hospital more often and had longer hospital stays compared with patients who began treatment. These untreated patients also had the highest costs associated with these hospital stays. In addition, patients who started treatments had longer hospital stays after their disease worsened. These findings suggest that timely treatment may reduce the need for hospital care. The study also highlights the need for new primary biliary cholangitis medications for patients who do not improve with initial treatments.
Key Summary Points
| Why carry out this study? |
| Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that predominantly affects women > 40 years of age, characterized by symptoms such as fatigue and pruritus, with a risk of progression to cirrhosis and end-stage liver disease. |
| Lack of or delayed treatment is associated with worse PBC outcomes and contributes to increased morbidity, mortality, and medical resource use. |
| This study assessed the real-world healthcare resource use (HRU) and costs of PBC in the USA. |
| What was learned from the study? |
| Substantial economic burden was observed in patients with PBC across different lines of treatment, including those not being treated. |
| This study emphasizes the importance of timely treatment for PBC to reduce HRU and medical costs and reveals the need for safer and more effective PBC treatments that can improve patient outcomes. |
Introduction
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that predominantly affects women > 40 years of age, with an estimated prevalence worldwide of 39.2 per 100,000 people [1, 2]. Most patients with PBC experience symptoms such as fatigue, abdominal pain, and pruritus [3]. Patients with untreated PBC are at risk of disease progression to cirrhosis and end-stage liver disease [1].
To date, treatment guidelines have recommended ursodeoxycholic acid (UDCA) as a first-line (1L) treatment for patients with PBC [4, 5]. Treatment with UDCA has been shown to improve prognosis and reduce mortality in patients with PBC [2]; however, among patients receiving UDCA as 1L treatment, about 40% have an inadequate response [6]. Until 2024, the only second-line (2L) treatment approved by the USA Food and Drug Administration (FDA) was obeticholic acid (OCA) [7]. Although some patients have shown favorable long-term responses to OCA even beyond the 12-month treatment window, OCA was voluntarily withdrawn from the USA market in September 2025 following a request from the USA FDA, who had previously noted insufficient evidence of OCA’s clinical benefit and increased risk of harm [8–11]. The FDA has placed a hold on all clinical trials conducted under a USA Investigational New Drug involving OCA [10]. Per the original 2018 American Association for the Study of Liver Diseases guideline recommendations for the treatment of PBC, fibrates have also been used for patients with incomplete response to UDCA [12]; however, their use is considered off-label in the USA and counter-indicated in patients with liver disease per their original label [13, 14]. Renal injury and renal insufficiency have been observed in patients with PBC treated with fibrates [15, 16]. Additionally, a not insignificant (5–10%) proportion of patients with PBC treated with fibrates report musculoskeletal problems [17]. Due to this unmet need for effective 2L therapies, two new treatments have been investigated for their efficacy in PBC and are now conditionally approved for use in combination with UDCA in adults who have an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA: elafibranor and seladelpar (approved in the USA on June 10, 2024, and August 14, 2024, respectively) [18–21]. Lack of or delayed treatment is associated with worse PBC prognosis and contributes to increased morbidity, mortality, and medical resource use [22–26]. According to existing literature, patients with PBC have high healthcare resource use (HRU) and healthcare costs [27–29]. However, research on HRU and costs across lines of therapy is lacking. This study aims to address the knowledge gap by describing HRU and healthcare costs among patients with PBC in the USA by line of treatment.
Methods
Data Source, Sample Identification, and Cohort Creation
This observational retrospective cohort study analyzed claims data from January 2016 to December 2022 from the IQVIA PharMetrics® Plus database, which contains integrated claims data of over 210 million beneficiaries (primarily people covered by commercial plans) in the USA since 2006. This study used IQVIA Pharmetrics® Plus claims data obtained under license from IQVIA®, as per signed agreement between Ipsen and IQVIA®. The study was considered exempt research under 45 CFR § 46.104(d)(4) as it involved only the secondary use of data that were de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA), specifically, 45 Code of Federal Regulations (CFR) § 164.514. Adult patients aged ≥ 18 years with diagnosed PBC on or after January 1, 2017, were identified based on International Classification of Disease, 9th Revision, Clinical Modification code 571.6 or 10th Revision (ICD-10-CM) code K74.3. Patients were eligible for inclusion if they had ≥ 1 inpatient (IP) non-diagnostic claim or ≥ 2 distinct outpatient (OP) non-diagnostic claims with an ICD-10-CM diagnosis code of PBC, were covered by a commercial healthcare plan or a Medicare Advantage plan, and had continuous enrollment for 12 months prior to baseline. Patients were excluded if they had liver transplantation before the index date and if they had cirrhosis, hepatic decompensation, clinically significant portal hypertension, primary sclerosing cholangitis, or hepatocellular carcinoma during baseline.
From the eligible patients, three non-mutually exclusive patient cohorts by line of treatment were created: (1) an untreated cohort: patients with newly diagnosed PBC without any PBC treatment (i.e., UDCA, OCA, and fibrates) prior to the index date and during the entire follow-up period; (2) a 1L cohort: patients with continuous enrollment from initial PBC diagnosis to the index date who initiated UDCA as 1L treatment and had no exposure to OCA prior to the index date; (3) a second-line or more (2L+) cohort: patients with continuous enrollment from initial PBC diagnosis to index date who initiated 2L or more treatment (i.e., OCA or fibrates [i.e., fenofibrate and gemfibrozil]) after 1L treatment with UDCA and had no exposure to OCA before the index date. The index date was defined as the date of PBC diagnosis for the untreated cohort, 1L treatment initiation for the 1L cohort, and 2L treatment initiation for the 2L+ cohort (Fig. 1). For all cohorts, the baseline period was defined as 12 months before the index date. The follow-up period for the untreated cohort extended from the index date to initiation of 1L treatment, death, end of continuous enrollment, or end of data, whichever of the four occurred first. For the 1L cohort, the follow-up period extended from the index date to 2L treatment initiation, death, end of continuous enrollment, or end of data, whichever of the four occurred first. For the 2L+ cohort, the follow-up period extended from the index date to death, end of continuous enrollment, or end of data, whichever of the three occurred first. A cohort selection flowchart with detailed sample selection criteria is presented in Fig. 2.
Fig. 1.
Index date, baseline period, and follow-up period for each cohort. 1L first-line, 2L(+) second-line (or more), PBC primary biliary cholangitis, UDCA ursodeoxycholic acid
Fig. 2.
Sample selection and creation of patient cohorts. Selected conditions/procedure during baseline period or any time before index include liver cirrhosis, hepatic decompensation, clinically significant portal hypertension, primary sclerosing cholangitis, and hepatocellular carcinoma during baseline period and liver transplant any time before the index date. 1L first-line, 2L(+) second-line (or more), IP inpatient, OCA obeticholic acid, OP outpatient, PBC primary biliary cholangitis, UDCA ursodeoxycholic acid
Study Outcomes and Statistical Analysis
Key patient characteristics and comorbidities during the baseline period were described using mean and standard deviation (SD) for continuous variables and counts and percentages for categorical variables. All-cause per-patient per-year (PPPY) HRU and healthcare costs during the baseline and follow-up periods were calculated for each cohort. For HRU, the annualized number of IP admissions, OP admissions, and emergency room (ER) visits and length of stay (LOS) for IP admission were summarized for each cohort. For healthcare costs, annualized medical costs (total and by category, such as IP admission, OP visits, ER visits, and other medical services [services outside of IP admission, OP visits, ER visits, such as costs associated with durable medical equipment and dental or visual care]), pharmacy costs (total and categorized by costs of PBC-related medications [including UDCA, OCA, and fenofibrate] and other pharmacy costs [non-PBC-related medications]), and total healthcare costs (defined as the sum of total medical costs and total pharmacy costs) were summarized for each cohort. Healthcare costs were measured as total payments from payers, and all costs were adjusted and reported in 2023 USA dollars.
Statistical comparisons between baseline and follow-up period HRU and healthcare costs were conducted using generalized estimating equations (GEE). For HRU, GEE models with a negative binomial distribution and log-link function were used to estimate incidence rate ratios (IRRs). For healthcare costs, GEE models with a Tweedie distribution and a log link function were used to estimate mean cost differences.
Results
Sample Identification, and Cohort Creation
Of 9585 patients who were diagnosed with PBC on or after January 1, 2017, 609 patients were eligible for the untreated cohort, 1659 patients were eligible for the 1L cohort, and 181 patients were eligible for the 2L+ cohort (Fig. 2). The median follow-up duration was 15.0–18.5 months.
Baseline Characteristics
The mean age at index ranged from 52.9–54.5 years across the three cohorts, and > 77% of patients in each cohort were female. Over 90% of patients from each cohort were covered by a commercial plan (Table 1). Overall, patients in the 2L+ cohort had the highest baseline comorbidity burden, followed by the 1L and the untreated cohorts, as reflected by mean (SD) Charlson Comorbidity Index (CCI) values of 2.5 (0.9), 2.1 (1.4), and 1.4 (1.7), respectively. The most prevalent comorbidities, complications, or symptoms among patients with PBC in each cohort were dyslipidemia (36.9–54.7%), hypertension (40.4–43.6%), and fatigue (19.9–24.4%). While baseline fatigue appeared to be similar across the three study cohorts, the prevalence of baseline pruritus was highest in the 2L+ cohort, followed by the 1L and untreated cohorts (18.8%, 7.5%, and 5.1%, respectively) (Table 1).
Table 1.
Patient baseline characteristics at index
| Untreated (N = 609) |
1L (N = 1659) |
2L+ (N = 181) |
|
|---|---|---|---|
| Demographic characteristics | |||
| Age at index (years), mean ± SD | 52.9 ± 12.9 | 54.5 ± 10.5 | 54.0 ± 10.1 |
| Female, n (%) | 470 (77.2%) | 1465 (88.3%) | 161 (89.0%) |
| Insurance plan, n (%) | |||
| Commercial | 566 (92.9%) | 1548 (93.3%) | 172 (95.0%) |
| Medicare advantage | 43 (7.1%) | 111 (6.7%) | 9 (5.0%) |
| Clinical characteristics | |||
| CCI, mean ± SD | 1.4 ± 1.7 | 2.1 ± 1.4 | 2.5 ± 0.9 |
| Comorbid liver complications, n (%) | |||
| Autoimmune hepatitis | 30 (4.9%) | 200 (12.1%) | 29 (16.0%) |
| Liver fibrosis | 7 (1.1%) | 83 (5.0%) | 8 (4.4%) |
| Portal hypertension | 3 (0.5%) | 12 (0.7%) | 0 (0.0%) |
| Other comorbidities, complications, and symptoms, n (%) | |||
| Dyslipidemia | 225 (36.9%) | 806 (48.6%) | 99 (54.7%) |
| Hypertension | 246 (40.4%) | 707 (42.6%) | 79 (43.6%) |
| Fatigue | 148 (24.3%) | 404 (24.4%) | 36 (19.9%) |
| Type 2 diabetes | 104 (17.1%) | 251 (15.1%) | 35 (19.3%) |
| Urinary tract infection | 65 (10.7%) | 167 (10.1%) | 16 (8.8%) |
| Gallstone disease | 66 (10.8%) | 190 (11.5%) | 14 (7.7%) |
| Diarrhea | 65 (10.7%) | 141 (8.5%) | 14 (7.7%) |
| Pruritus | 31 (5.1%) | 125 (7.5%) | 34 (18.8%) |
| Osteoporosis | 33 (5.4%) | 112 (6.8%) | 19 (10.5%) |
| Raynaud’s syndrome | 22 (3.6%) | 58 (3.5%) | 4 (2.2%) |
| Autoimmune thyroid disease | 13 (2.1%) | 61 (3.7%) | 8 (4.4%) |
| Sjögren’s syndrome | 9 (1.5%) | 61 (3.7%) | 11 (6.1%) |
| Systemic lupus erythematosus | 16 (2.6%) | 48 (2.9%) | 7 (3.9%) |
| Ulcerative colitis | 21 (3.4%) | 33 (2.0%) | 2 (1.1%) |
| Crohn’s disease | 13 (2.1%) | 24 (1.4%) | 1 (0.6%) |
| 2L treatment use, n (%) | |||
| OCA | – | – | 125 (69.1%) |
| Fibrates | – | – | 56 (30.9%) |
The dash (–) represents data that are not available
1L first-line, 2L(+) second-line (or more), CCI Charlson Comorbidity Index, OCA obeticholic acid, PBC primary biliary cholangitis, SD standard deviation
Healthcare Resource Use
During the 12-month baseline period, the untreated cohort incurred more IP admissions and ER visits than the 1L or 2L+ cohorts (mean [SD] IP admission [PPPY]: 0.21 [0.63], 0.14 [0.69], and 0.18 [0.91]; mean [SD] ER visits [PPPY]: 0.92 [1.57], 0.65 [1.26], and 0.67 [1.88], respectively). Similarly, the untreated cohort had the highest proportion of patients with at least one IP admission, followed by the 1L cohort and the 2L+ cohort (14.0% versus [vs.] 9.3% vs. 8.8%, respectively). Mean (SD) annualized OP visits (PPPY) was highest for the 2L+ cohort, followed by the 1L cohort and the untreated cohort (21.65 [16.53] vs. 20.68 [15.95] vs. 18.45 [18.20], respectively).
Within each cohort, HRU during the follow-up period increased from the 12-month baseline period, with the untreated cohort seeing the largest increase (Fig. 3). The mean (SD) number of OP visits (PPPY) was higher during the follow-up period compared with the 12-month baseline period (23.52 [22.78] vs. 18.45 [18.20]; IRR: 1.27, p < 0.001) for the untreated cohort. Mean (SD) OP visits also increased for the 1L cohort (22.02 [19.83] vs. 20.68 [15.95]; IRR: 1.07, p = 0.001), and for the 2L+ cohort (22.25 [19.65] vs. 21.65 [16.53]; IRR: 1.03, p = 0.633). The mean (SD) number of IP admissions (PPPY) similarly increased during the follow-up period compared with the 12-month baseline period for the untreated cohort (0.93 [5.52] vs. 0.21 [0.63]; IRR: 4.48, p < 0.001). In contrast, the mean (SD) number of IP admissions (PPPY) did not significantly change for the 1L cohort (0.16 [0.77] vs. 0.14 [0.69], IRR: 1.10, p = 0.519) or the 2L+ cohort (0.19 [0.84] vs. 0.18 [0.91], IRR: 1.09, p = 0.697). The mean (SD) IP LOS (PPPY) was significantly longer during the follow-up period than in the 12-month baseline period for the untreated cohort (7.45 [44.58] vs. 1.77 [7.92] days, IRR: 4.21, p < 0.001) and the 2L+ cohort (1.77 [11.59] vs. 0.83 [4.58] days, IRR: 2.12, p = 0.001). Conversely, the mean (SD) IP LOS (PPPY) was not significantly longer in the 1L cohort (1.12 [9.18] vs. 0.93 [6.46] days, IRR: 1.21, p = 0.435). There were no significant differences in the mean number of ER visits between the baseline and follow-up periods for any of the cohorts.
Fig. 3.
Per-patient per-year healthcare resource use during baseline and follow-up periods. 1L first-line, 2L(+) second-line (or more), CI confidence interval, ER emergency room, HRU healthcare resource use, IP inpatient, IRR incidence rate ratio, OP outpatient, PPPY per-patient per-year
During the follow-up period, the proportion of patients with IP admissions was highest in the untreated cohort, followed by the 2L+ cohort and the 1L cohort (24.6% vs. 16.0% vs. 12.4%, respectively). Compared with other cohorts, a higher proportion of patients in the untreated cohort had IP admissions during the follow-up period (PPPY; 2.0-times and 1.5-times the 1L and 2L+ cohorts, respectively), higher mean number of IP admissions (PPPY; 6.0-times and 4.9-times the 1L and 2L+ cohorts, respectively), and longer mean IP length of stay (PPPY; 6.6 times and 4.2 times the 1L and 2L+ cohorts, respectively).
Healthcare Costs
During the 12-month baseline period, mean (SD) total healthcare costs (PPPY) were highest for untreated patients, followed by patients on 1L therapy and patients on 2L+ treatments ($20,206 [$43,264] vs. $17,744 [$36,771] vs. $17,651 [$29,230], respectively). These healthcare costs included mean (SD) total medical costs (PPPY) of $15,671 ($38,276), $14,459 ($33,436), and $12,480 ($27,575) and mean (SD) total pharmacy costs (PPPY) of $4535 ($16,897), $3285 ($12,442), and $5171 ($9018) for the untreated, 1L, and 2L+ cohorts, respectively. In terms of medical services, cost of OP visits was the largest component across all cohorts at baseline, accounting for 53.8–65.7% of total medical costs and 39.6–53.5% of the total healthcare costs. Mean (SD) cost of OP visits (PPPY) was highest for the untreated cohort, followed by the 1L and 2L+ cohorts ($8245 [$21,207] vs. $9499 [$17,769] vs. $6982 [$10,036], respectively) (Table 2).
Table 2.
All-cause per-patient per-year healthcare costs (2023 USD) during baseline and follow-up periods
| (a) Untreated cohort | ||||
|---|---|---|---|---|
| Untreated (N = 609) | ||||
| Baseline | Follow-up | Mean cost difference (95% CI) Follow-up vs. baseline |
p value | |
| PPPY costs, mean ± SD | ||||
| Total healthcare costs | 20,206 ± 43,264 | 59,220 ± 279,134 | 39,015 (23,778, 54,518) | < 0.001 |
| Total medical costs | 15,671 ± 38,276 | 54,201 ± 278,470 | 38,530 (23,302, 54,028) | < 0.001 |
| OP | 8425 ± 21,207 | 14,298 ± 34,426 | 5873 (3953, 7766) | < 0.001 |
| ER | 1310 ± 3385 | 1855 ± 8326 | 545 (74, 1017) | 0.023 |
| IP | 5885 ± 27,243 | 37,974 ± 273,027 | 32,088 (17,131, 47,342) | < 0.001 |
| Other medical services | 51 ± 243 | 74 ± 298 | 24 (4, 42) | 0.016 |
| Total pharmacy costs | 4535 ± 16,897 | 5019 ± 17,256 | 484 (167, 711) | 0.002 |
| PBC treatments | – | – | – | – |
| Other pharmacy costs | 4535 ± 16,897 | 5019 ± 17,256 | 484 (167, 711) | 0.002 |
| (b) 1L cohort | ||||
|---|---|---|---|---|
| 1L (N = 1659) | ||||
| Baseline | Follow-up | Mean cost difference (95% CI) Follow-up vs. baseline |
p value | |
| PPPY costs, mean ± SD | ||||
| Total healthcare costs | 17,744 ± 36,771 | 23,056 ± 56,828 | 5312 (3383, 7170) | < 0.001 |
| Total medical costs | 14,459 ± 33,436 | 16,184 ± 53,708 | 1725 (− 131, 3518) | 0.069 |
| OP | 9,499 ± 17,769 | 9377 ± 27,231 | − 123 (− 1110, 824) | 0.772 |
| ER | 882 ± 2690 | 887 ± 3368 | 5 (− 125, 135) | 0.941 |
| IP | 4021 ± 25,148 | 5854 ± 42,622 | 1833 (286, 3359) | 0.020 |
| Other medical services | 56 ± 299 | 66 ± 474 | 10 (− 11, 29) | 0.367 |
| Total pharmacy costs | 3285 ± 12,442 | 6872 ± 16,068 | 3587 (3388, 3788) | < 0.001 |
| PBC treatments | – | 2251 ± 3639 | – | – |
| Other pharmacy costs | 3285 ± 12,442 | 4621 ± 15,617 | 1336 (1140, 1528) | < 0.001 |
| (c) 2L+ cohort | ||||
|---|---|---|---|---|
| 2L+ (N = 181) | ||||
| Baseline | Follow-up | Mean cost difference (95% CI) Follow-up vs. baseline |
p value | |
| PPPY costs, mean ± SD | ||||
| Total healthcare costs | 17,651 ± 29,230 | 76,144 ± 84,820 | 58,492 (49,945, 66,883) | < 0.001 |
| Total medical costs | 12,480 ± 27,575 | 17,613 ± 45,286 | 5133 (1259, 8979) | 0.009 |
| OP | 6982 ± 10,036 | 9613 ± 27,807 | 2632 (131, 5163) | 0.039 |
| ER | 1156 ± 4370 | 1052 ± 3217 | − 104 (− 402, 199) | 0.507 |
| IP | 4312 ± 20,663 | 6898 ± 28,771 | 2587 (− 57, 5167) | 0.055 |
| Other medical services | 31 ± 103 | 50 ± 212 | 19 (1, 38) | 0.038 |
| Total pharmacy costs | 5171 ± 9018 | 58,531 ± 73,644 | 53,359 (50,499, 55,933) | < 0.001 |
| PBC treatments | 1776 ± 1665 | 53,698 ± 73,211 | 51,922 (44,214, 59,470) | < 0.001 |
| Other pharmacy costs | 3395 ± 8856 | 4833 ± 11,242 | 1438 (1025, 1881) | < 0.001 |
The dash (–) represents data that are not available
1L first-line, 2L(+) second-line (or more), CI confidence interval, ER emergency room, IP inpatient, OP outpatient, PBC primary biliary cholangitis, PPPY per-patient per-year, SD standard deviation, USD United States dollar
Compared with the baseline period, patients incurred significantly higher healthcare costs during the follow-up period across all cohorts: mean annualized total healthcare costs (PPPY) during the follow-up vs. baseline period increased by $39,015 (p < 0.001) for the untreated cohort, $5312 (p < 0.001) for the 1L cohort, and $58,492 (p < 0.001) for the 2L+ cohort. For the untreated cohort, the increase in mean healthcare costs was driven by the increase in medical costs, especially the increase in costs of IP admissions by $32,088 (p < 0.001). For the 2L+ cohort, the increase in healthcare costs from baseline to follow-up was driven by the increase in pharmacy costs, especially the increase in PBC treatment costs by $51,922 (p < 0.001) (Table 2).
Comparing healthcare costs across the three cohorts during the follow-up period, patients in the untreated cohort had higher medical costs than the 1L and 2L+ cohorts: mean (SD) OP cost (PPPY) was $14,298 ($34,426) vs. $9377 ($27,231) vs. $9613 ($27,807); mean (SD) ER cost (PPPY) was $1855 ($8326) vs. $887 ($3368) vs. $1052 ($3217); mean (SD) IP cost (PPPY) was $37,974 ($273,027) vs. $5854 ($42,622) vs. $6898 ($28,771). Patients in the 2L+ cohort had the highest PBC medication cost, followed by the 1L cohort and untreated cohort (mean [SD] PBC medication cost [PPPY]: $53,698 [$73,211] vs. $2251 [$3639] vs. $0 [$0]) (Table 2).
Discussion
This retrospective real-world observational study is the first to assess economic burden in patients diagnosed with PBC in the USA by line of treatment. Our findings indicate that the comorbidity burden of patients with PBC increased with lines of treatment (mean CCI was 1.4, 2.1, and 2.5 for the untreated, 1L, and 2L+ cohorts, respectively). In addition, the proportion of patients with common PBC-related complications, comorbidities, and symptoms, such as autoimmune hepatitis, dyslipidemia, hypertension, pruritus, and osteoporosis, increased from the untreated cohort to 1L and 2L+ cohorts, highlighting the progressive nature of PBC.
The study reported a substantial economic burden for patients with PBC, with patients in all three cohorts experiencing significantly higher HRU during follow-up compared with the baseline period. For the untreated cohort, the increase in healthcare costs was driven by the significant increase in medical costs (mean cost difference [PPPY] of $38,530, p < 0.001). Compared with the 1L and 2L+ cohorts, patients in the untreated cohort had higher HRU (higher rate of IP admissions and longer IP LOS) and greater medical costs during follow-up, likely explained by the worse prognosis and poorer survival associated with lack of treatment [30]. These findings emphasize the importance of timely treatment in reducing the healthcare burden of PBC.
For the 1L and 2L+ cohorts, significantly higher HRU during follow-up was observed for the mean number of OP visits within the 1L treatment cohort and mean IP length of stay within the 2L+ treatment cohort. Total medical costs also increased following the initiation of 1L and 2L treatment (mean cost difference [PPPY] of $1725, p = 0.069 for the 1L cohort and $5133, p = 0.009 for the 2L+ cohort). These increases may be explained by lack of response to current mainstay therapies and the adverse events associated with them, underscoring the unmet need for safer and more effective therapies that can better manage PBC symptoms and slow disease progression.
Strengths and Limitations
To our knowledge, this is the first study to assess the HRU and cost burden associated with each line of treatment of PBC, and it provides insight into the challenges that patients face as their condition worsens. Another key finding of this study is that it reports on the burden of PBC among a younger patient population than what was observed a decade ago, which may be attributed to earlier detection and diagnosis of the disease (due to increased awareness and availability of treatments) [17], earlier occurrence of disease [31], or a combination of both. Notably, a previous study using 2005–2014 National Inpatient Sample (NIS) data estimated average annual IP costs of $17,059; however, this study did not report the use of PBC-related medications, so it was not possible to identify patients by line of treatment during the study period. It is also important to note that the prior study also assessed an older population, associated with more severe disease than the current study: the mean age of individuals in the NIS study was 63 years old, more than 56% of patients were covered by Medicare, and all patients had at least one IP admission during the data period [29]. Additional studies have reported costs for patient populations in which more than half the individuals were ≥ 65 years of age. One study reported estimated mean annual total payments of $797 for OP services and $22,860 for IP services using 5% Medicare data (2005–2015) [28]. Another study used data from a national database of administrative claims from 2016–2019 and reported mean monthly IP costs of $3905 and $6568 for mean monthly total healthcare costs [27]. The current study extends existing literature by specifically delving into the distinct economic implications of different lines of treatments in a younger and more contemporaneous patient population. In addition, the findings provide insights on the value of novel treatments for PBC and highlight the need for timely, effective interventions. Recent advances in the PBC therapeutic landscape offer the potential to reduce the economic burden of PBC; however, these therapies were not available at the time of this analysis. Future studies should investigate the impact of these therapies as data become available.
A significant strength of this study is that the methodology captures data that reflect the real-world experience of patients living with PBC in the USA with commercial insurance. As such, the patient population included in this study is much broader than the patient populations observed in clinical trials, which often have narrower inclusion and exclusion criteria. Therefore, the study results show high external validity, with the findings demonstrating an updated economic overview of patients living with PBC that is more representative of the broader USA population.
As with any analyses using administrative claims data, this study is subject to general limitations, such as the potential for incorrectly documented diagnosis codes and inability to capture medical services or pharmacy dispensing obtained outside of a patient’s plan. Most of the beneficiaries in the PharMetrics® database are covered by commercial plans, so the results from this study may not be generalizable to patients with PBC who have different access to care, such as uninsured patients or those covered by other plans not captured in the PharMetrics® database. Laboratory testing results are not available in the PharMetrics® database. As such, some important prognosis factors for this disease that are routinely measured to assess treatment response, such as the levels of alkaline phosphatase and total bilirubin, cannot be evaluated in the current study. Reasons for non-treatment are also unavailable, meaning it is not possible to ascertain why patients in the untreated cohort were initially untreated and whether the lack of treatment itself or other confounding factors contributed toward higher medical costs and longer hospital stays compared with the 1L and 2L+ cohorts. As the untreated cohort included patients with PBC who did not receive treatments during the study period, the untreated cohort could include patients who were diagnosed with PBC and were less willing or unable to receive pharmacological treatments; it has been estimated that 33% of patients with symptomatic PBC have never received treatment [32]. Data that could account for differences in care, such as socioeconomic status, residential location (e.g., urban vs. rural), and education status, were not available in the PharMetrics® database; this lack of demographic data is a common limitation associated with claims data analyses. Therefore, the analyses in this study were not adjusted for factors that could account for differences in care and PBC prognosis, and subsequently HRU and costs. These factors, or other underlying health inequities, may explain variations in economic burden. However, it is important to note that the study aimed to provide an overview of the economic burden of PBC and did not aim to establish causal relationships. Since PBC is a chronic disease, a longer study period would be warranted to appropriately measure the risk and cost of negative clinical outcomes, such as the need for a liver transplant, death, etc. Finally, this study is a relatively short-term snapshot of the economic burden of disease. Longer follow-ups are warranted from a healthcare system perspective, especially given the longevity of the studied condition, to properly capture all long-term effects and implications of PBC.
Conclusions
Substantial economic burden was observed in patients with PBC across different lines of treatment, including those not being treated, emphasizing a growing need for timely interventions for PBC. While the development of novel, effective PBC treatments could improve patient outcomes and reduce HRU and medical costs, it is important to recognize other factors that may influence this burden, such as the effect of socioeconomic factors on access to treatment. Future research should further explore the impact of timely treatment on both clinical outcomes and the long-term economic burden in PBC and examine how confounding factors may impact economic burden.
Acknowledgments
Medical Writing/Editorial Assistance
The authors thank Jose Medrano, PhD, and Marielle Brown, PhD, of Costello Medical, USA for providing medical writing support, which was sponsored by Ipsen in accordance with Good Publication Practice 2022 guidelines.
Author Contributions
Substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: Sonal Kumar, Nisreen Shamseddine, Hongbo Yang, Su Zhang, Dongni Ye, Shravanthi Seshasayee, Jingyi Chen, Kris V. Kowdley; drafting of the publication, or revising it critically for important intellectual content: Sonal Kumar, Nisreen Shamseddine, Hongbo Yang, Su Zhang, Dongni Ye, Shravanthi Seshasayee, Jingyi Chen, Kris V. Kowdley; final approval of the publication: Sonal Kumar, Nisreen Shamseddine, Hongbo Yang, Su Zhang, Dongni Ye, Shravanthi Seshasayee, Jingyi Chen, Kris V. Kowdley. All authors agree to be accountable for all aspects of the work. All authors agree for the final version of the manuscript to be published.
Funding
This study and publication development were sponsored by Ipsen. The journal’s Rapid Service Fee and Open Access Fee were funded by Ipsen.
Data Availability
Restrictions apply to the availability of these data since the data underlying this publication were provided by IQVIA® under contract to Ipsen.
Declarations
Conflict of Interest
Sonal Kumar: Consultant: Gilead, Madrigal, GSK, Boehringer Ingelheim, Intercept Pharmaceuticals, Ipsen, Novo Nordisk; Speaker and/or received honoraria from Madrigal, GSK, Novo Nordisk, Ipsen, Intercept Pharmaceuticals, Gilead; Nisreen Shamseddine: Employee of Ipsen; Hongbo Yang, Su Zhang, Dongni Ye, Shravanthi Seshasayee, Jingyi Chen: Employees of Analysis Group Inc., which received consulting fees from Ipsen; Kris V. Kowdley: Received grants from: Boston Scientific, Corcept, CymaBay, GENFIT, Gilead, GlaxoSmithKline, Hanmi, Intercept, Ipsen, Janssen, Madrigal, Mirum, Novo Nordisk, NGM, Pfizer, Pliant, Terns, Viking, Zydus, 89bio Inc.; Received royalties or licenses from UpToDate; Received consulting fees from: CymaBay, Enanta, GENFIT, Gilead, HighTide, Inipharm, Intercept, Ipsen, Madrigal, Mirum, NGM, Pliant, Pfizer, Protagonist, Zydus, 89bio Inc.; Received payment or honoraria from AbbVie, Gilead, Intercept; Received payment for expert testimony from the Department of Justice; Participant on a Data Safety Monitoring Board or Advisory Board for: CTI, Medpace, Labcorp, Worldwide Clinical Trials; Stockholder in Inipharm; Receipt of equipment, materials, drugs, medical writing, gifts, or other services from Velacur.
Ethical Approval
This study used IQVIA Pharmetrics® Plus claims data obtained under license from IQVIA®, as per signed agreement between Ipsen and IQVIA®. The study was considered exempt research under 45 Code of Federal Regulations (CFR) § 46.104(d)(4) as it involved only the secondary use of data that were de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA), specifically, 45 CFR § 164.514.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Lleo A, Wang G-Q, Gershwin ME, Hirschfield GM. Primary biliary cholangitis. Lancet. 2020;396(10266):1915–26. 10.1016/S0140-6736(20)31607-X. [DOI] [PubMed] [Google Scholar]
- 2.Lu M, Zhou Y, Haller IV, Romanelli RJ, VanWormer JJ, Rodriguez CV, et al. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment. Clin Gastroenterol Hepatol. 2018;16(8):1342–50.e1. 10.1016/j.cgh.2017.12.033. [DOI] [PubMed] [Google Scholar]
- 3.Laschtowitz A, de Veer RC, Van der Meer AJ, Schramm C. Diagnosis and treatment of primary biliary cholangitis. United Eur Gastroenterol J. 2020;8(6):667–74. 10.1177/2050640620919585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.European Association for the Study of the Liver. EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67(1):145–72. 10.1016/j.jhep.2017.03.022. [DOI] [PubMed] [Google Scholar]
- 5.Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Hepatology. 2022;75(4):1012–3. 10.1002/hep.32117. [DOI] [PubMed] [Google Scholar]
- 6.Corpechot C, Abenavoli L, Rabahi N, Chrétien Y, Andréani T, Johanet C, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 2008;48(3):871–7. 10.1002/hep.22428. [DOI] [PubMed] [Google Scholar]
- 7.United States Food and Drug Administration. OCALIVA® (obeticholic acid) Prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207999s008lbl.pdf. Accessed 14 Nov 2024.
- 8.Hirschfield G, Jones D, Carbone M, Bowlus CL, Nevens F, Kremer AE, et al. Long-term efficacy and safety of obeticholic acid in primary biliary cholangitis: responder analysis of over 5 years of treatment in the POISE trial. J Can Assoc Gastroenterol. 2021;4(suppl 1):229–31. 10.1093/jcag/gwab002.041.34738068 [Google Scholar]
- 9.Intercept Pharmaceuticals Inc. Intercept receives complete response letter from FDA addressing OCALIVA supplemental New Drug Application (sNDA) [press release]. 2024. https://www.interceptpharma.com/about-us/news/?id=2979130. Accessed 14 Nov 2024.
- 10.Intercept Pharmaceuticals Inc. Intercept Announces Voluntary Withdrawal of OCALIVA® for Primary Biliary Cholangitis (PBC) from the US Market; US Clinical Trials Involving Obeticholic Acid Placed on Clinical Hold [press release]. 2025. https://www.interceptpharma.com/about-us/news/?id=3148535.
- 11.Trauner M, Nevens F, Shiffman ML, Drenth JPH, Bowlus CL, Vargas V, et al. Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study. Lancet Gastroenterol Hepatol. 2019;4(6):445–53. 10.1016/S2468-1253(19)30094-9. [DOI] [PubMed] [Google Scholar]
- 12.Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394–419. 10.1002/hep.30145. [DOI] [PubMed] [Google Scholar]
- 13.Cancado GGL, Braga MH, Ferraz MLG, Villela-Nogueira CA, Terrabuio DRB, Cançado ELR, et al. Clinical features and treatment outcomes of primary biliary cholangitis in a highly admixed population. Ann Hepatol. 2022;27(1):100546. 10.1016/j.aohep.2021.100546. [DOI] [PubMed] [Google Scholar]
- 14.United States Food and Drug Administration. FENOGLIDE Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022118s010lbl.pdf. Accessed 29 Oct 2024.
- 15.Duan W, Ou X, Wang X, Wang Y, Zhao X, Wang Q, et al. Efficacy and safety of fenofibrate add-on therapy for patients with primary biliary cholangitis and a suboptimal response to UDCA. Rev Esp Enferm Dig. 2018;110(9):557–63. 10.17235/reed.2018.5533/2018. [DOI] [PubMed] [Google Scholar]
- 16.Levy C, Peter JA, Nelson DR, Keach J, Petz J, Cabrera R, et al. Pilot study: fenofibrate for patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid. Aliment Pharmacol Ther. 2011;33(2):235–42. 10.1111/j.1365-2036.2010.04512.x. [DOI] [PubMed] [Google Scholar]
- 17.Hirschfield GM, Dyson JK, Alexander GJM, Chapman MH, Collier J, Hübscher S, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568–94. 10.1136/gutjnl-2017-315259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Gilead. Gilead’s Livdelzi (Seladelpar) Granted Accelerated Approval for Primary Biliary Cholangitis by U.S. FDA. https://www.gilead.com/news/news-details/2024/gileads-livdelzi-seladelpar-granted-accelerated-approval-for-primary-biliary-cholangitis-by-us-fda. Accessed 29 Oct 2024.
- 19.Hirschfield GM, Bowlus CL, Mayo MJ, Kremer AE, Vierling JM, Kowdley KV, et al. A phase 3 trial of seladelpar in primary biliary cholangitis. N Engl J Med. 2024;390(9):783–94. 10.1056/NEJMoa2312100. [DOI] [PubMed] [Google Scholar]
- 20.Ipsen. Ipsen’s Iqirvo® receives U.S. FDA accelerated approval as a first-in-class PPAR treatment for primary biliary cholangitis. https://www.ipsen.com/press-releases/ipsens-iqirvo-receives-u-s-fda-accelerated-approval-as-a-first-in-class-ppar-treatment-for-primary-biliary-cholangitis/. Accessed 29 Oct 2024.
- 21.Kowdley KV, Bowlus CL, Levy C, Akarca US, Alvares-da-Silva MR, Andreone P, et al. Efficacy and safety of elafibranor in primary biliary cholangitis. N Engl J Med. 2024;390(9):795–805. 10.1056/NEJMoa2306185. [DOI] [PubMed] [Google Scholar]
- 22.Corpechot C, Carrat F, Bonnand A-M, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology. 2000;32(6):1196–9. 10.1053/jhep.2000.20240. [DOI] [PubMed] [Google Scholar]
- 23.Harms MH, Lammers WJ, Thorburn D, Corpechot C, Invernizzi P, Janssen HLA, et al. Major hepatic complications in ursodeoxycholic acid-treated patients with primary biliary cholangitis: risk factors and time trends in incidence and outcome. Am J Gastroenterol. 2018;113(2):254–64. 10.1038/ajg.2017.440. [DOI] [PubMed] [Google Scholar]
- 24.Locke GR III, Therneau TM, Ludwig J, Dickson ER, Lindor KD. Time course of histological progression in primary biliary cirrhosis. Hepatology. 1996. 10.1002/hep.510230108. [DOI] [PubMed] [Google Scholar]
- 25.Prince M, Chetwynd A, Newman W, Metcalf JV, James OF. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. Gastroenterology. 2002;123(4):1044–51. 10.1053/gast.2002.36027. [DOI] [PubMed] [Google Scholar]
- 26.Younossi ZM, Bernstein D, Shiffman ML, Kwo P, Kim WR, Kowdley KV, et al. Diagnosis and management of primary biliary cholangitis. Am J Gastroenterol. 2019;114(1):48–63. 10.1038/s41395-018-0390-3. [DOI] [PubMed] [Google Scholar]
- 27.Gish RG, Law A, Lingohr-Smith M, Adekunle F, Wheeler D, Velez De Villa B, et al. Primary biliary cholangitis: patient characteristics and the healthcare economic burden in the United States [AASLD abstract 1259]. Hepatology; 2020;72(suppl 1). https://doi.org/10.1002/hep.31578
- 28.Sayiner M, Golabi P, Stepanova M, Younossi I, Nader F, Racila A, et al. Primary biliary cholangitis in Medicare population: the impact on mortality and resource use. Hepatology. 2019;69(1):237–44. 10.1002/hep.30174. [DOI] [PubMed] [Google Scholar]
- 29.Shahab O, Sayiner M, Paik J, Felix S, Golabi P, Younossi ZM. Burden of primary biliary cholangitis among inpatient population in the United States. Hepatol Commun. 2019;3(3):356–64. 10.1002/hep4.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Trivella J, John BV, Levy C. Primary biliary cholangitis: epidemiology, prognosis, and treatment. Hepatol Commun. 2023;7(6):e0179. 10.1097/hc9.0000000000000179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Brind AM, Bray GP, Portmann BC, Williams R. Prevalence and pattern of familial disease in primary biliary cirrhosis. Gut. 1995;36(4):615–7. 10.1136/gut.36.4.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Mayo MJ, Carey E, Smith HT, Mospan AR, McLaughlin M, Thompson A, et al. Impact of pruritus on quality of life and current treatment patterns in patients with primary biliary cholangitis. Dig Dis Sci. 2023;68(3):995–1005. 10.1007/s10620-022-07581-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Restrictions apply to the availability of these data since the data underlying this publication were provided by IQVIA® under contract to Ipsen.