ABSTRACT
Background & Aims
This US‐based study assessed the impact of pruritus on health‐related quality of life (HRQoL) and treatment experiences of people with primary biliary cholangitis (PBC).
Methods
Patients with PBC were recruited from a physician panel and patient advocacy group. Participants were grouped by the Pruritus Numerical Rating Scale (NRS): No/Mild Pruritus (NMP, NRS < 4) and Moderate/Severe Pruritus (MSP, NRS ≥ 4). Participants completed the 5‐D Itch, PBC‐40, EQ‐5D‐5L, Chronic Liver Disease Questionnaire (CLDQ‐PBC), Work Productivity and Activity Impairment (WPAI), and Functional Assessment of Chronic Illness Therapy – Fatigue Scale, Version 4 (FACIT‐Fatigue) questionnaires, and PBC treatment experiences questions. Differences were analysed using regression models for confounders. An MSP group subset responded to voice questions.
Results
The sample included 40 NMP and 50 MSP participants, with 85% and 80% females, respectively. The MSP group reported significantly worse outcomes on 5‐D Itch, EQ‐5D Index, PBC‐40 (all domains besides Emotional), FACIT‐Fatigue, and CLDQ‐PBC total scores compared to the NMP group (all p < 0.05). The MSP group reported significantly greater activity impairment due to PBC (57%) than the NMP group (36%; p < 0.001). The MSP group had a lower employment rate (42%) than the NMP group (53%). Fewer than 25% of the MSP group were receiving itch treatment.
Conclusions
Individuals with PBC and pruritus report limited pruritus treatment use and minimal itch relief. Those with moderate/severe pruritus experience a greater HRQoL burden and reduced activity compared to those with mild/no pruritus. This highlights the need for effective treatments that ameliorate pruritus in patients with PBC.
Keywords: autoimmune liver disease, cholestatic pruritus, patient voice, patient‐reported outcomes, PBC, quality of life
Summary.
There is limited real‐world evidence on the impact of pruritus in primary biliary cholangitis (PBC) in the US. Our study shows that moderate‐to‐severe pruritus significantly worsens the quality of life for PBC patients; yet fewer than 25% receive treatments for pruritus due to their limited efficacy. This highlights the significant unmet need for better therapies to manage pruritus in PBC.
Abbreviations
- CLDQ
Chronic Liver Disease Questionnaire
- EQ‐5D‐5L
EuroQol 5‐Dimension 5‐Level
- FACIT‐Fatigue
Functional Assessment of Chronic Illness Therapy – Fatigue Scale
- FDA
Food and Drug Administration
- HCC
hepatocellular carcinoma
- HRQoL
health‐related quality of life
- MSP
moderate/severe pruritus
- NMP
no/mild pruritus
- NRS
numerical rating scale
- OCA
obeticholic acid
- PBC
primary biliary cholangitis
- PRO
patient‐reported outcome
- SD
standard deviation
- UDCA
ursodeoxycholic acid
- US
United States
- WPAI
Work Productivity and Activity Impairment
1. Introduction
Primary biliary cholangitis (PBC) is a progressive, chronic autoimmune liver disease characterised by immuno‐inflammatory destruction of small bile ducts (cholestasis) and the buildup of harmful bile acids [1, 2, 3]. If left untreated, PBC can lead to advanced fibrosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), liver failure, liver transplantation, and premature death [4, 5]. The estimated prevalence of PBC in the United States (US) is 39.2 per 100 000 individuals [4, 6], with estimates for the number of individuals in the US with PBC reaching as high as 130 000 [7].
Although patients with PBC may not exhibit symptoms at the time of diagnosis, most will eventually develop symptoms, typically 2–4 years after diagnosis [8]. The most common symptoms of PBC are cholestatic pruritus, sicca complex, and fatigue [5]. Patients with PBC may also report abdominal discomfort, joint pain, and bone pain [5]. Up to 70% of patients with PBC experience cholestatic pruritus during the course of their disease, and more than one‐third have moderate‐to‐severe itch [9, 10]. Severe cholestatic pruritus can be unbearable, leading to sleep deprivation, social isolation, and can trigger suicidal ideation [5, 11]. In extreme cases, pruritus can justify liver transplantation, even in the absence of cirrhosis or decompensated liver disease [5, 11]. Pruritus in PBC patients typically fluctuates over time and is generally not directly correlated with disease severity [12].
The impact of cholestatic pruritus on patients with PBC, particularly the stress and burden it causes, has not been extensively studied [13]. A US study utilising a longitudinal PBC cohort found that patients with clinically significant pruritus, defined as ≥ 7 on the PBC‐40 Itch domain, experienced significantly (p < 0.05) lower health‐related quality of life (HRQoL), as measured by the PBC‐40, the 5‐D Pruritus Scale (5‐D Itch Scale), and the PROMIS Fatigue Survey, compared to those with no or mild pruritus [10]. PBC impacts multiple domains of patients' lives, including HRQoL, itch, and sleep. However, the effects of pruritus on other areas, such as work productivity, have been less thoroughly studied.
Our current study provides a comprehensive evaluation of HRQoL in PBC patients experiencing pruritus, utilising multiple validated instruments. These include PBC‐specific measures like the PBC‐40 and the Chronic Liver Disease Questionnaire (CLDQ)‐PBC [14, 15, 16]. The Work Productivity and Activity Impairment (WPAI) Questionnaire, infrequently used in previous PBC studies, was included to offer new insights into how pruritus impacts work productivity and daily activities. Additionally, voice data provided qualitative insights into the painful nature of pruritus and its negative effects on emotional health and productivity, complementing quantitative assessments to enhance understanding of the patient experience.
As of early 2024, the standard treatment for PBC starts with ursodeoxycholic acid (UDCA) as the first‐line therapy [5, 8]. For patients who do not respond adequately or are intolerant to UDCA, obeticholic acid (OCA) is used as a second‐line treatment [5, 8]; however, OCA is contraindicated in patients with decompensated cirrhosis or compensated cirrhosis with evidence of portal hypertension due to the risk of serious liver injury, including liver failure and the need for liver transplantation [17]. In May 2021, the US Food and Drug Administration (FDA) issued a communication restricting the use of OCA in patients with PBC and advanced cirrhosis for these safety reasons [18]. In December 2024, the FDA reported additional cases of serious liver injury in PBC patients treated with OCA who did not have cirrhosis. That communication advised healthcare providers and patients of this new safety concern and emphasised the importance of frequent liver tests to detect worsening function and guide timely discontinuation of OCA [19]. The effectiveness of these therapies has been shown through changes in surrogate biochemical markers (e.g., alkaline phosphatase) [5, 20]. In addition to pharmacological approaches, non‐pharmacological solutions include cool morning showers, light therapy, and choosing breathable clothing [21].
Despite well‐established treatment guidelines and clinical evidence supporting the efficacy of UDCA and OCA, patients with PBC may discontinue treatment due to intolerance, incomplete response to therapy, or side effects [22]. Pruritus has been frequently cited as a reason for OCA discontinuation [23, 24, 25].
A real‐world study using a longitudinal cohort to evaluate the impact of pruritus on patients' quality of life found that pruritus in PBC patients is often undertreated, with only about half (51%) of patients with clinically significant pruritus receiving treatment for their pruritus [10]. Notably, this study did not provide reasons for why patients discontinued their previous treatments [10]. While some research has explored treatment patterns, there remains a need for further investigation into discontinuation patterns of PBC treatments and therapies for PBC‐related pruritus among US patients [23].
Given the limited research in this area in the US, obtaining patients' perspectives regarding the burden and unmet treatment needs of PBC‐related cholestatic pruritus is critical to raising awareness of their experiences, HRQoL, and psychosocial needs. Capturing the patient's voice may further illuminate the challenges they face, providing valuable insights that could guide more effective treatment and management strategies. Thus, the purpose of this observational, mixed methods study was to evaluate perceptions of pruritus and its impact on quality of life and well‐being among people living with PBC in the US. Additionally, this study examined patients' experiences with PBC treatments, including their overall perceptions, treatment patterns, and reasons for discontinuation.
2. Materials and Methods
2.1. Participant Selection
US participants were recruited (1) from the PBCers Organisation, the largest PBC online support group in the US, and (2) through physician panels that included patients with a physician‐confirmed PBC diagnosis. Participants first completed a screening survey to determine their eligibility for this study. Individuals who met the study eligibility criteria were asked to provide their informed consent electronically and then complete a questionnaire via their smartphones or computers. The study was approved by the WCG Institutional Review Board (IRB tracking ID: 20235194).
Patients with a diagnosis of PBC were eligible to participate if they were aged ≥ 18 years, living in the US, self‐reported that they were currently taking an FDA‐approved treatment for PBC (at the time of the study, either UDCA or OCA), and provided study informed consent. Patients were ineligible to participate if they were not taking/receiving either UDCA and/or OCA, were a current employee of CymaBay Therapeutics (a wholly owned subsidiary of Gilead Sciences Inc.) or had an immediate family member who was a current CymaBay Therapeutics employee, were unable to read or understand English, had neither a mobile device nor access to a computer, or were currently enrolled in a clinical trial for a PBC treatment at the time of the study. Patients taking UDCA, OCA, or both were eligible regardless of concurrent therapies (e.g., fibrates).
Based on the Pruritus NRS completed during screening, participants were categorised into two groups: (1) patients with a Pruritus NRS score of 0–3 were allocated to the No/Mild Pruritus (NMP) group; and (2) patients with a Pruritus NRS score of 4–10 were allocated to the Moderate/Severe Pruritus (MSP) group.
A subset of participants from the MSP group was also asked to respond to qualitative voice questions by calling into an automated voice response system. This qualitative voice questionnaire was open to the first 25 participants from the MSP group who agreed to complete the voice questions. Eligible individuals could participate in the voice response portion of the study by calling in and responding to each of the prompts by talking into their phone. They responded independently without a moderator present.
2.2. Power Calculation and Sample Size
A power calculation was conducted to determine the adequate sample size needed to test for differences between patients with moderate/severe pruritus (i.e., the MSP group) and patients without or with mild pruritus (i.e., the NMP group). Differences in HRQoL scores (PBC‐40 Itch domain scores) between PBC patients with and without pruritus from prior literature were used to estimate the expected difference between patients stratified into the NMP and MSP groups [10, 26]. An estimate of the minimum sample size needed to test for pre‐specified group differences at 80% power and α = 0.05 was calculated, resulting in a final target sample size of 90 patients.
2.3. Study Variables
All participants were asked about their demographics, diagnostic and treatment characteristics, pruritus severity, disease‐specific quality of life, health utility, fatigue, activity impairment, and work productivity.
Two patient‐reported outcome (PRO) measures were administered to gather data on pruritus. The Pruritus NRS is a validated, single‐item PRO measure that assesses the severity of pruritus on a 0–10 scale [27, 28]. The 5‐D Itch Scale is a validated 8‐item PRO assessing various aspects of pruritus, including the duration, degree, direction, disability (related to itching), and distribution (which body parts have been impacted) of pruritus [28, 29].
Several PRO assessments were administered to gather data on the impact of pruritus on patients' quality of life. The PBC‐40 is a validated 40‐item PRO assessing the domains of social, emotional, cognitive function, itch, fatigue, and other symptoms in patients with PBC [15, 28]. The PBC‐specific version of the CLDQ, the CLDQ‐PBC, is a new, validated 35‐item PRO assessing the domains of diet, fatigue, emotional health, itch, sleep, worry, and symptoms in patients with PBC [16]. The EuroQol 5‐Dimension 5‐Level (EQ‐5D‐5L) is a validated 6‐item PRO assessing the domains of usual activities, anxiety/depression, pain/discomfort, self‐care, and mobility [30]. In addition to the questions assessing these five dimensions, a sixth question includes a visual analogue scale (VAS) whereby participants rate their perceived health [30]. The Functional Assessment of Chronic Illness Therapy – Fatigue Scale, Version 4 (FACIT‐Fatigue) is a validated 13‐item PRO assessing fatigue, with higher scores indicating less fatigue and better quality of life [31].
The WPAI Questionnaire: General Health (WPAI:GH) V2.0 is a validated, 6‐item PRO measure that assesses the impact of health and symptoms on work productivity and daily activities [32, 33, 34].
Further details about the score ranges and score interpretation (e.g., a higher score indicates worse quality of life) for each instrument are provided in Table 2.
TABLE 2.
Unadjusted mean scores for PRO total and domain scores by NMP and MSP groups.
| Outcome | Score interpretation | Range of scores | NMP (N = 40), Mean (SD) | MSP (N = 50), Mean (SD) |
|---|---|---|---|---|
| 5‐D itch score | ||||
| Total | Higher score indicates more severe itch and negative impact | 5–25 | 9.7 (2.8) | 14.4 (3.5) |
| EQ‐5D‐5L score | ||||
| EQ‐5D index | Higher scores indicate better quality of life | −0.573−1.000 | 0.78 (0.2) | 0.63 (0.3) |
| EQ VAS | 1–100 | 64.4 (18.2) | 60.8 (17.5) | |
| PBC‐40 domain scores | ||||
| Symptoms | Higher scores indicate worse quality of life | 7–35 | 17.9 (4.8) | 20.9 (4.0) |
| Itch | 3–15 | 5.6 (2.0) | 8.9 (3.0) | |
| Fatigue | 11–55 | 30.2 (8.9) | 37.4 (8.2) | |
| Cognitive | 6–30 | 14.8 (5.1) | 19.1 (5.0) | |
| Emotional | 3–15 | 9.2 (3.3) | 10.4 (2.5) | |
| Social | 10–50 | 29.3 (9.1) | 35.6 (9.3) | |
| FACIT‐Fatigue score | ||||
| Total | Higher score indicates less fatigue | 0–52 | 32.2 (10.5) | 23.9 (12.0) |
| CLDQ‐PBC score | ||||
| Total | Higher score indicates better quality of life | 1–7 | 4.9 (1.0) | 3.9 (1.4) |
| CLDQ‐PBC domain scores | ||||
| Diet | Higher score indicates better quality of life | 1–7 | 5.1 (1.2) | 4.2 (1.4) |
| Emotional | 1–7 | 4.9 (1.4) | 4.1 (1.6) | |
| Fatigue | 1–7 | 4.6 (1.2) | 3.7 (1.3) | |
| Itch | 1–7 | 5.9 (1.3) | 4.1 (1.8) | |
| Sleep | 1–7 | 4.7 (1.6) | 3.8 (1.8) | |
| Symptoms | 1–7 | 5.0 (1.0) | 4.1 (1.2) | |
| Worry | 1–7 | 4.3 (1.9) | 3.5 (1.9) | |
| WPAI scores | ||||
| % activity impairment due to PBC | Higher scores indicate greater impairment or productivity loss | 0–100 | 36.3% | 56.6% |
| % work time missed due to PBC (absenteeism) a | 0–100 | 5.8% | 9.8% | |
| % impairment while working due to PBC (presenteeism) a | 0–100 | 32.4% | 46.5% | |
| % overall work impairment due to PBC a | 0–100 | 35.2% | 49.7% | |
Abbreviations: 5‐D Itch Scale, 5‐D Pruritus Scale; CLDQ, Chronic Liver Disease Questionnaire; EQ‐5D‐5L, EuroQol 5‐Dimension 5‐Level; FACIT‐Fatigue, Functional Assessment of Chronic Illness Therapy – Fatigue Scale; MSP, moderate/severe pruritus; NMP, no/mild pruritus; PBC, primary biliary cholangitis; SD, standard deviation; VAS, visual analogue scale; WPAI, Work Productivity and Activity Impairment Questionnaire.
WPAI scores (except for the activity impairment score) were calculated only for participants who indicated they were currently employed and provided complete and interpretable WPAI data (NMP: n = 21; MSP: n = 17). WPAI scores were excluded for four participants in the MSP group due to responses that were nonsensical and rendered the data uninterpretable.
Eight voice‐response questions inquired about PBC symptoms and the effects of PBC on daily life, with a particular focus on pruritus (referred to as “itch due to PBC” for participant understanding). These questions asked participants in the MSP group to describe pruritus and examine the effects of itching on HRQoL, emotional well‐being, and its physical, social, and financial impacts. The automated voice response system asked specific questions about the impact of itch, descriptors of this impact, treatment experiences, and the anticipated effect of improved treatments on their life.
2.4. Data Analysis
Descriptive statistics were used to analyse all variables in the study for both groups: NMP and MSP groups. Continuous variables were summarised using mean, standard deviation (SD), minimum, median, and maximum. Additional metrics for PRO scores included the 25th percentile, 75th percentile, interquartile range, and 95% confidence interval of the median. Categorical variables were reported as percentages and counts.
Differences in PRO scores between NMP and MSP groups were analysed using multivariable regression models, adjusting for age, gender, ethnicity, insurance, and treatment with UDCA and OCA. Due to the limited sample size of only seven patients receiving fibrates, the statistical model did not include adjustments for fibrate use. All analyses were conducted with either Microsoft Excel or R 4.4.0.
Voice data were analysed qualitatively through content analysis to identify salient themes. Representative patient quotes were highlighted and grouped by theme/topic.
3. Results
3.1. Participant Characteristics
A total of 159 individuals were recruited and completed the eligibility screener, of whom 122 (77%) met study eligibility criteria, and 90 (57%) participants completed the study (Figure 1). Of the 90 participants who completed the study, 28 were recruited through physician panels, and 62 were recruited through the PBCers Organisation. The 90 participants who completed the study were stratified into the NMP group (N = 40) and the MSP group (N = 50).
FIGURE 1.
Flow diagram of recruitment process. NRS, numerical rating scale; OCA, obeticholic acid; PBC, primary biliary cholangitis; UDCA, ursodeoxycholic acid. * Individuals answered all screening questions before being disqualified. Therefore, some individuals had multiple reasons for disqualification from this study.
Participants were mostly female, with a mean age of 56.7 years (SD: 12.1) in the NMP group and 52.1 years (SD: 12.2) in the MSP group (Table 1). The mean level of itch at baseline as measured by the Pruritus NRS was 1.3 for the NMP group and 6.2 for the MSP group. All participants in the study had health insurance coverage, with over half using private health insurance. The mean time to diagnosis from the initial presentation of disease‐related symptoms or first healthcare provider contact regarding these symptoms or other findings (e.g., laboratory abnormalities detected during routine screening) was 1.1 years (SD: 1.9) in the NMP group and 1.0 years (SD: 1.6) in the MSP group. PBC was most commonly initially suspected due to abnormal results found during routine blood work (60% in the NMP group; 64% in the MSP group). All patients had at least one comorbidity; the most common comorbidities were high blood pressure, anxiety, and Raynaud's syndrome. Seven (18%) and 10 (20%) participants had cirrhosis at the time of the study, with one (3%) and seven (14%) experiencing complications related to cirrhosis (variceal bleeding, ascites, or hepatic encephalopathy) in the NMP and MSP groups, respectively (Table 1).
TABLE 1.
Patient characteristics.
| Variable | NMP (N = 40) | MSP (N = 50) |
|---|---|---|
| Recruitment avenue, n (%) | ||
| Physician panel | 10 (25) | 18 (36) |
| PBCers advocacy group | 30 (75) | 32 (64) |
| Gender | ||
| Female, n (%) | 34 (85) | 40 (80) |
| Male, n (%) | 5 (13) | 10 (20) |
| Non‐binary, n (%) | 1 (3) | 0 (0) |
| Ethnicity a | ||
| White, n (%) | 31 (78) | 36 (72) |
| Hispanic or Latino, n (%) | 3 (8) | 8 (16) |
| Black or African American, n (%) | 3 (8) | 5 (10) |
| Native American or American Indian, n (%) | 1 (3) | 0 (0) |
| Asian/Pacific Islander, n (%) | 0 (0) | 3 (6) |
| Other, n (%) | 6 (15) | 4 (8) |
| Age (years) | ||
| Mean (SD) | 56.7 (12.1) | 52.1 (12.2) |
| Median | 56.0 | 52.0 |
| Age at PBC diagnosis (years) | ||
| Mean (SD) | 48.9 (11.6) | 44.5 (9.5) |
| Median | 48.0 | 45.5 |
| Time to PBC diagnosis (years) | ||
| Mean (SD) | 1.1 (1.9) | 1.0 (1.6) |
| Years since PBC diagnosis | ||
| Mean (SD) | 7.7 (8.5) | 7.6 (6.8) |
| Median | 3.0 | 4.5 |
| Mean level of itch at baseline | ||
| Itch score (SD) b | 1.3 (1.2) | 6.2 (1.7) |
| Health insurance coverage a | ||
| Overall, n (%) | 40 (100) | 50 (100) |
| Private Insurance, n (%) | 21 (53) | 26 (52) |
| Medicare, n (%) | 9 (23) | 8 (16) |
| Medicaid/CHIP, n (%) | 5 (13) | 17 (34) |
| VA/DoD/TRICARE, n (%) | 1 (3) | 1 (2) |
| Other, n (%) | 6 (15) | 4 (8) |
| Comorbidities a | ||
| High blood pressure, n (%) | 10 (25) | 11 (22) |
| Raynaud's syndrome, n (%) | 9 (23) | 3 (6) |
| Anxiety, n (%) | 9 (23) | 11 (22) |
| Diabetes, n (%) | 5 (13) | 5 (10) |
| Sjögren's syndrome, n (%) | 4 (10) | 5 (10) |
| High cholesterol, n (%) | 3 (8) | 3 (6) |
| Asthma, n (%) | 3 (8) | 5 (10) |
| Rheumatoid arthritis, n (%) | 1 (3) | 1 (2) |
| Bipolar/psychotic disorders, n (%) | 0 (0) | 2 (4) |
| Fibromyalgia/chronic fatigue syndrome, n (%) | 0 (0) | 3 (6) |
| Other c , n (%) | 9 (23) | 5 (10) |
| Cirrhosis status | ||
| Cirrhosis of the liver, n (%) | 7 (18) | 10 (20) |
| Complications due to cirrhosis, n (%) | 1 (3) | 7 (14) |
| Employment status d | ||
| Employed, n (%) | 21 (53) | 21 (42) |
| Unemployed, n (%) | 19 (47) | 29 (58) |
Abbreviations: CHIP, Children's Health Insurance Program; DoD, Department of Defense; MSP, moderate/severe; NMP, no/mild pruritus; PBC, primary biliary cholangitis; SD, standard deviation; VA, Veterans Affairs.
Participants were asked to select all applicable responses, allowing for multiple selections. Therefore, the responses were not mutually exclusive.
As measured by Pruritus Numerical Rating Scale (NRS); No/Mild Pruritus = Pruritus NRS score of 0–3 and Moderate/Severe Pruritus = Pruritus NRS score of 4–10.
In the NMP group, other comorbidities were the following: lupus, limited scleroderma, cirrhosis, Hashimoto's thyroiditis, Sjogren's syndrome, irritable bowel syndrome (IBS), and thyroid. In the MSP group, other comorbidities were the following: achalasia, atrial fibrillation, chronic obstructive pulmonary disease (COPD), Crohn's disease, Hashimoto's thyroiditis, and hypothyroidism.
WPAI scores (except for the activity impairment score) were calculated only for participants who indicated they were currently employed and provided complete and interpretable WPAI data (NMP: n = 21; MSP: n = 17). WPAI scores were excluded for four participants in the MSP group due to responses that were nonsensical and rendered the data uninterpretable.
3.2. Patient‐Reported Outcomes
The unadjusted mean scores for the PBC‐40, CLDQ‐PBC, FACIT‐Fatigue, 5‐D Itch, EQ‐5D‐5L, and WPAI by NMP and MSP groups are presented in Table 2. Directionally, patients in the MSP group had worse scores across each of the domains of all of the PRO measures included in this study compared to the NMP group.
Table 3 presents the regression results for each of the PRO measures, controlling for age, gender, ethnicity, and treatment. Figure S1 also presents the results of the regression analysis, highlighting which group experienced worse outcomes for each PRO measure/domain, along with interpretations of these results.
TABLE 3.
Regression results assessing differences in PRO scores by NMP and MSP groups. a
| Outcome | Coefficient (MSP vs NMP Group) | 95% CI | p |
|---|---|---|---|
| 5‐D itch score | |||
| Total | 4.87 | (3.56, 6.18) | < 0.001 |
| EQ‐5D‐5L score | |||
| EQ‐5D Index | −0.14 | (−0.24, −0.04) | 0.005 |
| EQ VAS | −3.58 | (−11.01, 3.85) | 0.348 |
| PBC‐40 domain scores | |||
| Symptoms | 2.26 | (0.55, 3.97) | 0.011 |
| Itch | 4.18 | (2.91, 5.45) | < 0.001 |
| Fatigue | 7.24 | (3.63, 10.85) | < 0.001 |
| Cognitive | 3.53 | (1.43, 5.63) | 0.001 |
| Emotional | 0.72 | (−0.46, 1.90) | 0.239 |
| Social | 4.18 | (0.67, 7.69) | 0.022 |
| FACIT‐Fatigue score | |||
| Total | −8.26 | (−12.85, −3.67) | < 0.001 |
| CLDQ‐PBC score | |||
| Total | −0.87 | (−1.38, −0.36) | < 0.001 |
| CLDQ‐PBC domain scores | |||
| Diet | −0.75 | (−1.27, −0.23) | 0.006 |
| Emotional | −0.66 | (−1.22, −0.10) | 0.024 |
| Fatigue | −0.92 | (−1.42, −0.43) | < 0.001 |
| Itch | −1.73 | (−2.32, −1.14) | < 0.001 |
| Sleep | −0.82 | (−1.50, −0.13) | 0.022 |
| Symptoms | −0.87 | (−1.31, −0.43) | < 0.001 |
| Worry | −0.35 | (−1.02, 0.32) | 0.306 |
| WPAI scores | |||
| % activity impairment due to PBC | 0.20 | (0.08, 0.32) | < 0.001 |
| % work time missed due to PBC (absenteeism) b | 0.04 | (−0.06, 0.14) | 0.349 |
| % impairment while working due to PBC (presenteeism) b | 0.17 | (−0.03, 0.37) | 0.236 |
| % overall work impairment due to PBC b | 0.13 | (−0.07, 0.33) | 0.204 |
Note: As an example, a regression coefficient of 4.87 indicates that being in the MSP group is associated with an increase in the 5‐D Itch total score by 4.87 points (scores range from 5–25, with higher scores indicating more severe itch and negative impact).
Abbreviations: 5‐D Itch Scale, 5‐D Pruritus Scale; CI, confidence interval; CLDQ, Chronic Liver Disease Questionnaire; EQ‐5D‐5L, EuroQol 5‐Dimension 5‐Level; FACIT‐Fatigue, Functional Assessment of Chronic Illness Therapy – Fatigue Scale; MSP, moderate/severe pruritus; NMP, no/mild pruritus; PBC, primary biliary cholangitis; SD, standard deviation; VAS, visual analogue scale; WPAI, Work Productivity and Activity Impairment Questionnaire.
Adjusting for age, gender, ethnicity, obeticholic acid, and ursodeoxycholic acid treatment.
WPAI scores (except for the activity impairment score) were calculated only for participants who indicated they were currently employed and provided complete and interpretable WPAI data (NMP: n = 21; MSP: n = 17). WPAI scores were excluded for four participants in the MSP group due to responses that were nonsensical and rendered the data uninterpretable.
Compared with the NMP group, the MSP group had significantly worse 5‐D Itch total scores (p < 0.001) and EQ‐5D Index scores (p = 0.005). Additionally, the MSP group had significantly worse PBC‐40 mean scores in the Symptom, Itch, Fatigue, Cognitive, and Social domains (all p < 0.05); but not in the Emotional domain (p = 0.239). The MSP group also had worse total FACIT‐Fatigue and CLDQ‐PBC scores (both p < 0.001) compared to the NMP group. Additionally, the MSP group had significantly lower (worse) CLDQ‐PBC scores across the Diet, Emotional, Fatigue, Itch, Sleep, and Symptoms domains (all p < 0.05).
Participants in the MSP group reported higher rates of sleep disturbance and daytime sleepiness than those in the NMP group. In the 5‐D Itch assessment, 45% of NMP participants indicated that itching “never affects sleep,” and another 45% indicated it “occasionally delays falling asleep,” compared to only 6% and 34% of MSP participants, respectively. More severe effects (“delays falling asleep and occasionally/frequently wakes me up at night”) were reported by 24% and 14% of MSP participants, versus 8% and 0% in the NMP group.
Data from the CLDQ‐PBC similarly highlighted the greater sleep‐related burden in the MSP group. Feeling sleepy during the day “all of the time” or “most of the time” was reported by 38% of MSP participants, versus 21% in the NMP group. Difficulty sleeping at night was reported at the same frequency (i.e., either “all of the time” or “most of the time”) by 36% of MSP participants, compared to 11% of NMP participants. Notably, 22% of MSP participants reported being disturbed by itching in their sleep “all of the time” or “most of the time,” compared to just 3% of NMP participants. These findings underscore a higher prevalence of pruritus‐associated sleep disruption in the MSP group.
The MSP group also reported significantly greater activity impairment due to PBC (57% in the MSP group vs 36% in the NMP group; p < 0.001). Additionally, the percentage of patients who were employed was lower in the MSP group (42%) compared to the NMP group (53%). Among employed individuals, the MSP group demonstrated higher rates of work absenteeism, decreased productivity while at work, and greater overall work‐related impairment from PBC compared to the NMP group. Differences in the WPAI scores related to work productivity were not statistically significant (Table 3).
Of the 21 patients working for pay in the NMP group and 17 in the MSP group, 6% and 10% of work time, respectively, was missed in the past week due to their health problem (absenteeism). Among the 19 (48%) patients in the NMP group and 29 (58%) in the MSP group who were not working for pay, a greater proportion of those in the NMP group were aged ≥ 65 (8 of 19, 42%) compared with the MSP group (5 of 29, 17%). This suggests that if age‐related retirement contributed to unemployment, its impact was likely more pronounced in the NMP group. Among these same patients not working for pay, the perceived impact of PBC on the ability to perform daily activities (other than paid work), rated on a scale from 0 (PBC had no effect on my daily activities) to 10 (PBC completely prevented me from doing my daily activities), averaged 4.1 in the NMP group and 5.7 in the MSP group. Additionally, 32% of work in the NMP group and 47% in the MSP group was impaired due to their health problem (presenteeism).
3.3. Patient Treatment Experience
The breakdown of PBC treatments for the NMP and MSP groups is presented in Table 4a. In the NMP group, most patients were treated with UDCA (88%) and/or OCA (18%). Similarly, in the MSP group, most patients were treated with UDCA (74%) and/or OCA (30%). A small percentage of patients were receiving treatment for their pruritus at the time of the study. Four patients (10%) from the NMP group were receiving at least one of the following treatments for pruritus: antihistamines, antibiotics, bile acid sequestrants, gabapentin, or opiate antagonists, compared to eleven patients (22%) from the MSP group. Among the 50 MSP participants, each of the following pruritus treatments was used by at least one participant: antihistamines, antibiotics, bile acid sequestrants, gabapentin, and opiate antagonists. In contrast, the use of antihistamines, bile acid sequestrants, and gabapentin was not observed in the NMP group.
TABLE 4a.
Current PBC treatment.
| NMP (N = 40) | MSP (N = 50) | |
|---|---|---|
| Current PBC treatment a | ||
| Ursodeoxycholic acid, n (%) | 35 (88) | 37 (74) |
| Obeticholic acid, n (%) | 7 (18) | 15 (30) |
| Fibrates, n (%) | 2 (5) | 5 (10) |
| Other, n (%) | 1 (3) | 3 (6) |
| Current pruritus treatments a | ||
| Antihistamines, n (%) | 0 (0) | 8 (16) |
| Antibiotics b , n (%) | 3 (8) | 4 (8) |
| Bile acid sequestrants, n (%) | 0 (0) | 2 (4) |
| Gabapentin, n (%) | 0 (0) | 1 (2) |
| Opiate antagonists, n (%) | 1 (3) | 1 (2) |
| Other, n (%) | 1 (3) | 3 (6) |
Abbreviations: MSP, moderate/severe pruritus; NMP, no/mild pruritus; PBC, primary biliary cholangitis.
Participants were asked to provide reasons for discontinuing their treatments. Multiple selections were allowed, so the responses were not mutually exclusive.
Rifampicin (rifampin) or vancomycin was the antibiotic included.
Patients discontinued UDCA and OCA for different reasons, with ineffectiveness being the most common (reported in 0% and 50% of UDCA and OCA discontinuations in the NMP group, and in 75% and 100% in the MSP group, respectively) (Table 4b). Other treatments, such as bile acid sequestrants, antihistamines, gabapentin, and fibrates, were also discontinued for various reasons, most commonly due to ineffectiveness or following doctor recommendations. Approximately two‐thirds of MSP group patients who discontinued bile acid sequestrants reported ineffectiveness as a reason for discontinuation (n = 8; 67%) (Table 4b). Table 4b provides details regarding the reasons for discontinuing PBC treatments over the past three years for all treatments.
TABLE 4b.
Reasons for discontinuing PBC treatments in the past 3 years. a
| NMP (N = 40), n (%) | MSP (N = 50), n (%) | |
|---|---|---|
| Ursodeoxycholic acid | 0 (0) | 4 (8) |
| Ineffective | — | 3 (75) |
| Side effects | — | 1 (25) |
| Preferred alternative therapy | — | 1 (25) |
| Symptoms improved | — | 1 (25) |
| Obeticholic acid | 2 (5) | 2 (4) |
| Ineffective | 1 (50) | 2 (100) |
| Side effects | 1 (50) | — |
| Doctor recommendation | 1 (50) | — |
| Other | 1 (50) | — |
| Fibrates | 1 (3) | 2 (4) |
| Ineffective | 1 (100) | 1 (50) |
| Side effects | — | 1 (50) |
| Doctor recommendation | — | 1 (50) |
| Antihistamines | 3 (8) | 3 (6) |
| Ineffective | 1 (33) | 2 (67) |
| Side effects | 1 (33) | — |
| Symptoms improved | — | 1 (33) |
| Other | 1 (33) | — |
| Antibiotics | 1 (3) | 1 (2) |
| Side effects | 1 (100) | — |
| Doctor recommendation | — | 1 (100) |
| Bile acid sequestrants | 1 (3) | 12 (24) |
| Ineffective | 1 (100) | 8 (67) |
| Side effects | — | 1 (8) |
| Cost | — | 2 (17) |
| Doctor recommendation | — | 5 (42) |
| Gabapentin | 1 (3) | 5 (10) |
| Ineffective | — | 4 (80) |
| Doctor recommendation | 1 (100) | — |
| Other | — | 1 (20) |
| Sertraline | 1 (3) | 0 (0) |
| Symptoms improved | 1 (100) | — |
Note: All reasons for discontinuation percentages are based on the number of patients discontinuing each specific drug.
Abbreviations: MSP, moderate/severe pruritus; NMP, no/mild pruritus; PBC, primary biliary cholangitis.
Participants were asked to provide reasons for discontinuing their treatments. Multiple selections were allowed, so the responses were not mutually exclusive.
3.4. Patient Voice Findings on Impact of PBC and Pruritus
Patient voice data highlighted the debilitating impact of PBC‐related itching. PBC‐related pruritus was described as unrelenting, deep, diffuse, mobile, and formication‐like (sensation of bugs crawling under one's skin), distinct from dermatological itches, with terms such as “sharpness,” “abrasion,” and “heat” used to describe it. Patients referred to their PBC as an “invisible illness” marked by fatigue, brain fog, and functional limitations. Many expressed significant anxiety and fear due to the uncertain prognosis. The detrimental effect of itch on job performance was highlighted, with several patients noting that lack of sleep and the itch itself make focusing on work difficult. The burdens of pruritus negatively impact emotional well‐being, especially due to its constant, unrelenting nature. See Table 5 for exemplary quotes describing the impact of PBC and pruritus from the patients' perspective.
TABLE 5.
Exemplary quotes from patients collected using the voice response system.
| Themes | Exemplary quotes a |
|---|---|
| Description of pruritus: patients describe pruritus presents as unrelenting, deep, diffuse, mobile, and formication‐like itch, which is unlike dermatologically based itches | “It's an itch that's so far down in your system, almost like to your bones in a way.” |
| “The way that I experience it is mainly it feels like a bunch of very tiny bugs are crawling just underneath the first layer of your skin. And you can't quite move them, you can't get them away, and they are just constantly crawling in every direction.” | |
| Description of emotional effects related to PBC and the uncertain prognosis: patients describe feelings of anxiety and stress as a result of an uncertain future | “So, that thing hanging over your head of, ‘Do I have an expiration date over my head?’ And no one can tell you for sure yes or no, which is sometimes part of life, but you're a lot more aware of it on a day‐to‐day basis… it can be really overwhelming, especially when you think of your kids, especially when you think of your partner.” |
| Description of fatigue: patients describe fatigue as an overwhelming and pervasive symptom of PBC that severely limits their daily activities and overall energy | “PBC in my daily life is mostly something hanging over me, the biggest thing being the fatigue. It lays over you like a blanket all the time. You have the itch as well, but the biggest day to day… is that fatigue of never going to be having enough energy, never going to have as much energy as you used to have.” |
| Description of cognitive effects: patients describe brain fog, memory loss, and confusion lead to a functional deficit, preventing patients from thinking clearly and recalling information as they would like | “I feel that PBC is a problem that on occasion can affect your mental stability. It can make you have a foggy brain. It can also make you forget things. There can be some days where you're so tired that you don't feel like you want to get out of bed. There are also days when you're working that it's difficult to maybe complete your assignment without taking a break.” |
| Description of the impact on sleep: patients explain that they believe they would be able to sleep through the night without the itch | “I might actually be able to sleep most nights, unlike what I'm doing now… It's nearly impossible to get comfortable when you're busy scratching all the time.” |
| Description of impacts on work: patients explain how itch impacts their work by distracting them and making it ‘hard to focus’ or accomplish tasks | “It's hard for me to sleep, and then I have a hard time at work, hard time focusing. And then, on top of that, I'm itching while I'm at work, which makes it very hard to focus, it's very distracting, and very hard to get anything done. So, I'm less productive.” |
| Description of emotional effects related to pruritus: patients describe feelings of frustration as a result of persistent itching | “I know it's been very frustrating at times when I'm just trying to sit down and watch a movie… I'm itching so hard I can't focus on the movie, and I'm like, I can't even relax. So, emotionally that's really hard, when you can't relax at certain points, because this itching is just constant…” |
| Description of the impact of treatments on patients' itching: patients report trying numerous topical and oral treatments available over the counter and by prescription to treat their itching | “I tried everything that you can buy in the supermarket that's topical. I even saved some [cream] that I had for surgery procedure and experimented with my own concoctions, and I know that's not good, but that didn't work either. So, I don't know.” |
All patient quotes were from participants in the MSP group.
3.5. Patient Voice Findings – Perceptions of Pruritus Treatment
Patients reported trying various over‐the‐counter and prescription topical and oral treatments to relieve their itching, but most reported receiving little to no relief from PBC‐related pruritus. For those who experienced relief, the effects were described as brief or minimal. Patients expressed frustration by the lack of effective treatments, with some options failing to address the itch and causing side effects like drowsiness. They reported a desire for lasting relief that also prevents liver damage, describing such improvement as “fantastic,” “a miracle,” allowing them to “be like a normal person,” and “actually sleep.” See Table 5 for a quotation from a patient about their experience with pruritus treatments.
4. Discussion
This study demonstrates that patients with moderate‐to‐severe pruritus experience a significantly greater negative impact on HRQoL than those without pruritus or with mild pruritus, across a broad range of domains, including those related to itch, fatigue, and social and cognitive function. The MSP group had significantly lower health utility values and more impaired activity compared to the NMP group. The findings from validated PRO measures are further supported by patient voice data, which emphasise how the persistent nature of pruritus substantially impairs productivity, social functioning, and emotional well‐being. Additionally, WPAI Questionnaire data revealed differences in non‐work activities and employment rates between the MSP and NMP groups.
The WPAI questionnaire has had limited use in studies assessing work productivity among patients with PBC [35]. Our WPAI analysis showed significantly greater non‐work activity impairment in patients with moderate/severe pruritus compared to those with no/mild pruritus (p < 0.001). Employment rates were also lower in the MSP group (42%) compared to the NMP group (53%). Among employed individuals, the MSP group reported more missed work, higher work‐related impairment, and greater overall work impairment due to PBC. These differences did not reach statistical significance, potentially because less than half of the participants (47%) were employed. The impact on patients' ability to work (absenteeism) and their productivity at work (presenteeism) has implications for the financial burden patients may face because of their PBC‐related pruritus. One study analysing published literature found that the costs of presenteeism could be up to three times those of absenteeism in the US [36]. Further research is required to quantify the indirect costs associated with PBC‐related absenteeism and presenteeism.
Our findings are consistent with earlier studies on the impact of PBC on patients' HRQoL [10], confirming that those with more severe pruritus have worse scores across multiple domains, including symptoms, physical health, cognitive function, and social and emotional well‐being. The present study builds upon previous research by comprehensively assessing various aspects of pruritus in PBC, with a particular focus on its impact on HRQoL in PBC patients. To evaluate HRQoL, multiple validated instruments were administered, including the PBC‐40, CLDQ‐PBC, 5‐D Itch, EQ‐5D‐5L, and FACIT‐Fatigue. As previously noted, the WPAI Questionnaire was used to assess the impact of pruritus on work productivity and activity impairment, an area not extensively explored in prior studies on this population. Notably, the PBC‐40 and CLDQ‐PBC, two well‐established tools specifically designed for PBC patients, were included, both of which have demonstrated reliability and validity in this population [10, 14, 15, 16].
Although no significant differences were observed between the NMP and MSP groups in the Emotional domain of the PBC‐40 (p = 0.239), several factors may have contributed to this finding. One possibility is that patients experience emotional adaptation over time, which may attenuate measurable differences between groups, even when disparities in other symptom domains are present [37]. Additionally, because the PBC‐40 Emotional domain assesses the emotional impact of PBC as a whole, the overall emotional burden of the disease, given its morbidity and mortality, may influence patients in addition to the impact of changing symptoms.
PBC is also associated with sleep disturbances [38]. Findings from our study were consistent with prior literature, with participants in the MSP group reporting higher rates of (1) sleep disruption due to itching, as measured by the 5‐D Itch, and (2) daytime sleepiness, difficulty sleeping at night, and being disturbed by itching during sleep, as measured by the CLDQ‐PBC, compared to those in the NMP group.
Despite the substantial impact of pruritus on patients' quality of life, only 22% of those in the MSP group were taking treatment for pruritus, with limited efficacy being the most common reason for discontinuation (Table 4b). Low awareness of pruritus burden and available treatment options may also be contributors to the low proportion of patients treated for pruritus [13]. Notably, OCA use was higher in the MSP group (30% vs 18% in the NMP group); thus, the possibility of OCA‐induced pruritus may be slightly higher in this group, as OCA is known to exacerbate pruritus in some patients. A systematic literature review recently published identified a lack of reliable evidence regarding the effectiveness, quality of life impact, and safety of treatments for cholestatic pruritus. Consequently, clinicians are often forced to rely on clinical experience rather than evidence‐based medicine when selecting treatment approaches [13]. Consistent with this, our study found that antihistamines were the most commonly used medication among patients receiving pruritus treatment, despite antihistamines not being recommended as first‐line therapy in current European Association for the Study of the Liver and American Association for the Study of Liver Diseases guidelines [5, 8, 39].
Together, these findings highlight the need for (1) better education about PBC, its associated symptoms, and available treatments, (2) improved strategies for guideline implementation, and (3) more efficacious drugs specifically for the management of pruritus in PBC.
Patients reported intense pruritus and stressed that effective treatment could improve well‐being and reduce anxiety, fatigue, and isolation. Patient voice data underscores the value of a treatment that alleviates pruritus, with one participant with moderate‐to‐severe pruritus remarking that such a treatment would be “a miracle, [allowing them] to actually go out again and do things that [they] enjoy.”
The precise cause of pruritus in PBC remains elusive [40]. Disturbances in bile acid homeostasis are believed to contribute to cholestatic itch, and treatments that reduce bile acid levels may have the potential to alleviate pruritus [40]. In a clinical trial of seladelpar in patients with PBC, reductions in interleukin‐31 and bile acids were closely correlated with improvements in pruritus, suggesting a potential mechanism for the observed antipruritic effects [41].
Strengths of this study include the inclusion of an ethnically diverse patient population that is comparable to the general PBC population in terms of patient characteristics. The mixed‐methods approach, which combines validated PRO instruments to assess quality of life with a voice response system to capture the patient's perspective, enhances the validity of our research and offers a more holistic understanding of the patients' experiences. Moreover, the comprehensiveness of the PROs included along with the consistency of the results adds robustness and reliability to these findings. Treatment experiences were captured and expanded on previous research by collecting data on the reasons patients discontinue PBC treatments. Finally, this study encompasses patients with PBC who exhibit a wide spectrum of pruritus experiences, ranging from no pruritus to severe pruritus.
While the generalizability of the findings to the broader PBC population may be limited by the small sample size, it is important to note that the target sample size was determined based on a power calculation focused on differences in HRQoL. The low proportion of employed participants likely resulted in insufficient statistical power to detect significant differences between groups on work productivity variables. For example, the limited number of employed participants may specifically affect the applicability of the results to the broader working population. Some participants were recruited via advocacy groups, and although they may have had a confirmed diagnosis of PBC, this information could not be verified; therefore, the possibility of misclassification bias cannot be ruled out. Other limitations include potential recall bias, a common issue in patient surveys, which may affect the accuracy of self‐reported data. Data were not explicitly collected regarding the presence of other comorbid conditions potentially associated with pruritus (e.g., eczema, dermatitis); thus, the possibility that these conditions may have influenced the assessment of PBC‐specific pruritus cannot be excluded. Regarding treatments evaluated, the study did not examine specific medication doses, titration schedules, or combinations of therapies. In our study, all participants were insured; uninsured individuals may have different treatment experiences due to potential differences in access to care. Lastly, the mechanism underlying PBC‐related pruritus is not fully understood, so attributing pruritus specifically to PBC cannot be definitively confirmed.
This study expands on prior analyses and provides further evidence that people with PBC, representing diverse racial and ethnic backgrounds, who have moderate‐to‐severe pruritus experience reduced activity and a greater HRQoL burden compared to those with mild/no pruritus. Despite this, individuals with PBC who experience this symptom report infrequent use of treatments targeting pruritus (itching), with minimal or no relief from their itch. There is a clear unmet need for safe and effective treatments that address pruritus and improve associated HRQoL outcomes. As emerging therapies are developed for patients with PBC to address unmet medical needs, future research should focus on the patient experience, particularly pruritus, given its far‐reaching negative impacts on HRQoL.
Author Contributions
C.F.M.P., J.I., Z.M.Y., R.Z., D.I., and B.P. contributed to the study concept and design, questionnaire development, and interpretation of the results. R.Z., D.I., and B.P. were responsible for study execution, ethics approval, data collection, and statistical analysis. C.L., Z.M.Y., M.J.M., A.E.K., and J.P. contributed to the discussion and interpretation of findings. All authors critically revised the manuscript for important intellectual content, contributed significantly to finalising the manuscript, and approved the final version for publication.
Conflicts of Interest
C.L. has served as a consultant to Gilead Sciences, Intercept, Ipsen, Mirum, CymaBay, GSK, Calliditas, and Kowa. She has received research grants/contracts from Gilead Sciences, Intercept, Mirum, Zydus, CymaBay, GSK, Escient, Calliditas, Ipsen, and Kowa. She has also participated in a Data Safety Monitoring Board for COUR Pharmaceuticals. Z.M.Y. has received research funding and/or served as a consultant to Intercept, CymaBay, Boehringer Ingelheim, BMS, GSK, Novo Nordisk, Ipsen, AstraZeneca, Siemens, Madrigal, Merck, and Abbott. J.I. and C.F.M.P. are employees of Gilead who, in the course of their employment, have received stock options exercisable for, and other stock awards of, ordinary shares of Gilead Sciences. R.Z., B.P., and D.I. are employees of Stratevi, a research consulting firm that received funding from Gilead Sciences, previously CymaBay, to conduct this study. M.J.M. has received grants or contracts from CymaBay, Genfit, Gilead Sciences, GSK, Ipsen, and Mirum Pharma. She has received consulting fees from CymaBay, GSK, Intra‐Sana, Ipsen, Ironwood, Mallinckrodt, and Mirum Pharma. She has also received support for attending meetings and/or travel from CymaBay, GSK, Ipsen, and Mallinckrodt. A.E.K. has received grants or contracts from Gilead and Intercept. He has received consulting fees from AbbVie, Advanz Pharma, Alentis, Alfasigma, AstraZeneca, Avior Bio, Bayer, BMS, CymaBay, Escient, Falk, Gilead, GSK, Guidepoint, Intercept, Ipsen, Mirum Pharma, Merck Sharp & Dohme, Novo Nordisk, Roche, and Takeda. He has also received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AbbVie, Advanz Pharma, AOP Orphan, Bayer, BMS, CymaBay, Falk, Gilead, GSK, Intercept, Ipsen, Johnson & Johnson, Medscape, Mirum Pharma, Merck Sharp & Dohme, NewBridge, Novartis, Roche, Vertex, and Viofor. He has also received support for attending meetings and/or travel from Gilead and participated on a data safety monitoring board with AbbVie, Advanz Pharma, Alentis, Alfasigma, AstraZeneca, Avior Bio, Bayer, BMS, CymaBay, Escient, Falk, Gilead, GSK, Guidepoint, Intercept, Ipsen, Mirum, Merck Sharp & Dohme, Novo Nordisk, Roche, and Takeda. A.E.K. has had a leadership or fiduciary role (paid or unpaid) with PBC Foundation, Swiss Association for the Study of the Liver, Swiss Gastroenterology Society, Swiss Hepa, and Swiss Transplant Society.
Supporting information
Figure S1: PRO outcomes by group based on regression analysis: no/mild pruritus (NMP) vs moderate/severe pruritus (MSP).
Acknowledgements
We gratefully acknowledge the contributions of Roy Arguello, who conducted the data analysis, and Chris Bly, who assisted in the development of the content for this manuscript. We are grateful for the support and contributions of the PBCers Organisation, an online and in‐person support group for individuals with PBC, their care partners, and healthcare team members in assisting with patient recruitment.
Levy C., Younossi Z. M., Mayo M. J., et al., “Assessment of PBC Pruritus From the ITCH‐E Study: Quality of Life, Productivity, and Treatment Experiences,” Liver International 45, no. 9 (2025): e70276, 10.1111/liv.70276.
Funding: This study was funded by Gilead Sciences Inc.
Jonathan Ieyoub was affiliated with CymaBay Therapeutics at the time the study was conducted.
Handling Editor: Dr. Alessio Aghemo
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1: PRO outcomes by group based on regression analysis: no/mild pruritus (NMP) vs moderate/severe pruritus (MSP).
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.