Health-related quality of life, work productivity, and persisting challenges in treated ulcerative colitis patients: a Japanese National Health and Wellness Survey

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Intest Res. 2025;.ir.2024.00104

Publication date (electronic) : 2025 January 2

doi : https://doi.org/10.5217/ir.2024.00104

Sakiko Hiraoka¹, Zhezhou Huang², Fei Qin², Fatima Megala Nathan Arokianathan^,3, Kiran Davé⁴, Shweta Shah⁵, Hyunchung Kim⁶

¹Department of Gastroenterology, Okayama University, Okayama, Japan

²Cerner Enviza, Shanghai, China

³Oracle Life Sciences, Singapore

⁴Bristol Myers Squibb, Uxbridge, UK

⁵Bristol Myers Squibb, Princeton, NJ, USA

⁶Bristol Myers Squibb, Tokyo, Japan

Correspondence to Fatima Megala Nathan Arokianathan, Oracle Life Sciences, Oracle Corporation Singapore Pte. Ltd., Fusionopolis Galaxis Level 12, 1 Fusionopolis Place, (S) 138522, Singapore. E-mail: megala.nathan.arokianathan@oracle.com

Received 2024 July 2; Revised 2024 October 9; Accepted 2024 October 23.

Abstract

INTRODUCTION

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease (IBD) characterized by superficial mucosal inflammation and ulcers on the inner lining of the colon [1]. The global prevalence varies, with the highest rates observed in developed countries. In North America and Europe, the prevalence of UC has been reported as approximately 200–500 cases per 100,000 individuals [2]. In Japan, despite UC being designated as an intractable disease, the annual prevalence in 2014 showed a 10-fold increase in 10 years, while the incidence rate rose from 0.6 per 100,000 person-years in 2010 to 12.7 per 100,000 person-years in 2019, representing a more than 10-fold increase in 9 years [3].

Current treatment guidelines in Japan include early remission and recurrence prevention. As the most common treatment for remission induction therapy, 5-aminosalicylic acid (5-ASA) is prescribed for UC patients with mild-to-moderate severity. When inadequate response or intolerance to standard 5-ASA treatment occurs, steroids such as budesonide and prednisone are recommended to induce remission, while carotegrast methyl may be prescribed for moderate severity UC patients [4-7]. In steroid-refractory or steroid-dependent UC patients, the use of treatments such as immunomodulators/immunosuppressants (IMs/ISs) and biologic drugs have increased in recent years [8,9]. However, despite the availability of these different treatment types, unmet needs persist with limited Japanese studies reporting the impact of treatment types on patients work productivity and activity impairment (WPAI) and health-related quality of life (HRQoL) [10-12]. While the use of 5-ASA is effective in induction of remission of moderate UC, remission appears dose-dependent and required a prolonged duration of treatment compared to steroids [13]. For steroids and certain biologicals (e.g., adalimumab and golimumab), prolonged use was associated with an increased risk of adverse effects, centered along increased risk of infections [14-16].

The impact of UC on mental and emotional health issues stems from the disease outcomes, including abdominal pain and diarrhea during the disease’s active phase, disrupting a patient’s HRQoL [17]. While bowel urgency and incontinence are the 2 key elements of patient burden in UC, a study among the Japanese patient population revealed that both elements were underreported due to a potential discomfort in relaying the symptoms to healthcare professionals [18]. Moreover, studies have reported patients with moderate-to-severe UC having increased morbidity, poorer HRQoL, and severe impairment of social engagements [18,19]. Studies on UC have reported undesired outcomes impacting patients’ professional lives, with effects on increased absence and lack of confidence in the workplace [20]. Patients across Europe and Japan reported missing work due to worrying about the symptoms of UC rather than experiencing the actual symptoms [21,22]. Furthermore, studies have indicated that Japanese patients with IBD experienced greater mental strain. This increased burden is attributed to a “self-critical” mindset regarding their condition and a prevalent stigma against seeking counseling, unlike patients in other regions [22].

Although advanced treatments (e.g., ustekinumab and tofacitinib) have shown clinical benefits, the high costs have not always met the financial allocations of disease management and healthcare resources [23]. A study from the United States revealed that the annual mean cost of $1,077 (in US dollars) per patient, resulting in cost of illness of $22 million [24]. In Japan, a claims data study reported an annual medical cost of $1,457 per patient, with $249 million attributed towards total treatment cost [25].

A study reported the impact of UC on the indirect cost among Japanese patients surmounted to approximately 2 million Japanese Yen (¥), further emphasizing the disease burden in working individuals [26]. Hence, there remains a high unmet need for treatments, especially as the disease severity increases, increases on the healthcare burden and negative impact on society is observed as well.

While large epidemiological studies have been conducted across various regions in Asia, limited real-world evidence of the disease burden in Japanese UC patients remains [10,27,28]. Hence, the objective was to understand the disease burden and current unmet needs in UC patients treated with the standard of care and investigate how certain factors (e.g., treatment type, disease severity, and differences in working age groups) may impact the HRQoL and work productivity loss in treated UC patients utilizing data from the Japan National Health and Wellness Survey (NHWS). Additionally, the study aimed to quantify work productivity loss and indirect cost among employed patients with UC.

METHODS

1. Study Design

This was a retrospective, cross-sectional, observational study utilizing existing data from the Japan NHWS database of online survey responses conducted in 2017, 2019, and 2021. As an online-based questionnaire, it is self-administered to adults aged ≥ 18 years. A flowchart representing the study population is as detailed in Fig. 1. It consists of a base survey component used to assess demographics, disease experienced, and diagnosed, and measures such as HRQoL and WPAI [29], capturing vitality through the widely used 12/32-item Short Survey Instrument (SF-12/32) [30,31]. The survey is projected to reflect the general population using known population incidences for key characteristics. Eligible respondents are recruited through an existing, general purpose, internet-based consumer panel that is maintained by Lightspeed Research and its partnering companies [32]. The added uniqueness of the survey is the recruitment of panel members that are not strictly based on convenience but instead, such as in this study, an attempt was made to estimate the adult population distribution in Japan (e.g., age and sex). For example, in a study conducted in Japan, the sex was 52% versus 49% females in the adult population and in the panel respectively, accounting for clear similarities. Although the stratified sampling in the study did not account for additional factors (e.g., education), the NHWS sample in general, remains comparable to the population, with reference to the studied characteristics [33-35]. Furthermore, to substantiate, various peer-reviewed publications have previously compared the NHWS with other governmental sources [36-38]. The NHWS was reviewed by Pearl Institutional Review Board (Indianapolis, IN, USA; #17-KANT-150 [2017], #19-KANT-211 [2019], #21-KANT-256 [2021]) and granted exemption status. As patient identification in the database is anonymized, no personally identifiable information is included in the database and patients provided informed consent prior to participating.

Fig. 1.

Schematic of treated ulcerative colitis (UC) patients included in the study. A total of 30,001 participants were enrolled in the Japan National Health and Wellness Survey (NHWS) in 2017, 30,006 in 2019 and 30,015 in 2021. The cross-sectional survey conducted separately in 2017, 2019, and 2021 included participants who experienced UC, diagnosed by a physician, and currently using prescription medication. All other participants who did not fulfill the criteria were excluded from the study. The data from different people obtained at the time of each separate survey totaled to 293 UC patients on prescription medication.

RESULTS

1. Treated UC Patient Characteristics and Disease Burden

This study included 293 treated UC patients of which more than half were male (55.6%) and aged 40-64 years (51.2%). About two-thirds of patients were employed (64.2%), 61.8% had a university degree or above and 47.4% earned an ≥ mean Japanese family income (¥5,000,000) (Table 1). The majority of UC patients were non-biologics/JAKi users (83.6%), with most reported as 5-ASA monotherapy users (67.2%) and 16.4% received either steroids or IMs/ISs. Patients self-reported having moderate-to-severe disease severity posttreatment (34.8%). Close to a third were living with UC for ≥ 15 years (29.0%) and more than half (55.3%) experienced ≥ 1 persisting UC symptom. Loose stool or diarrhea (28.7%), abdominal pain or cramping (19.5%), and tiredness or fatigue (18.1%) were commonly reported (Table 2).

Table 1.

Demographic and General Health Characteristics of Treated Ulcerative Colitis Patients

Table 2.

Clinical Characteristics of Treated UC Patients

Despite active treatment (5-ASA, steroids, IMs/ISs, and/or biologics/JAKi), 91.5% self-reported UC as bothersome, ranging from “somewhat” to “extremely” (Fig. 2A) and over a third (≥ 35%) experienced varying severity levels of depressive and/or anxiety-related symptoms (Fig. 2B). In terms of HRQoL, a mean ± SE of 68.1 ± 1.3 was reported for the EQ VAS score, while the mean scores for MCS and PCS measured by SF-36v2 were 46.3 ± 10.5 and 50.4 ± 7.2, respectively (Fig. 2C).

Fig. 2.

Disease burden of ulcerative colitis (UC). (A) Patient-reported perception of UC based on bothersome levels. (B) Patient-reported depression measured by 9-item Patient Health Questionnaire (PHQ-9) and anxiety measured by 7-item Generalized Anxiety Disorder survey (GAD-7). (C) Patient-reported health-state utility measured by EuroQoL visual analog scale (EQ VAS) and health-related quality of life (HRQoL) measured by 32-Item Short Survey Instrument version 2–mental component score (MCS) and physical component score (PCS). Measurements were based on a scale of 0–100, with higher scores reflecting better health outcomes. Data are expressed as mean±standard error.

2. Overall WPAI and Indirect Cost Outcomes in Treated UC Patients

A total of 200 of the 293 treated UC patients reported some level of activity impairment. Of 188 employed patients, 21 patients who did not respond to the questionnaire were considered as missing values. Of the eligible 167 employed patients without missing values for overall work impairment, 54 (32.3%) patients reported no impairment, while 113 (67.7%) reported overall work impairment. Majority of employed patients reported absenteeism (mean ± SE: 5.7% ± 1.27%) and presenteeism (mean ± SE: 27.6% ± 2.06%), with 98.4% (167 patients) and 89.4% (168 patients), respectively. On mean, employed patients reported ≥ 40.0% work productivity loss in the 113 patients, resulting in a mean annual indirect cost per patient of ¥1.1 million ($10.2 thousand) (Fig. 3 and Supplementary Table 2).

Fig. 3.

The mean work productivity and activity impairment (WPAI) and the indirect cost resulting from work productivity loss per patient/year. The sample sizes pertaining to absenteeism (n=168), presenteeism (n=185), and overall work impairment (n=167; n=54 reported 0% and n=113 reported >0%) relied on patients who provided responses to relevant questionnaires within the employed patient population. Indirect cost comprised of results of absenteeism and presenteeism costs. Data are expressed as mean±standard error. aJapanese Yen (¥1,000=$6.44).

Multivariate analysis conducted showed higher WPAI was associated with being male, single, having an mean family income < ¥5,000,000, being drinkers, experiencing moderate-to-severe disease severity, and having low medication adherence (P<0.05). Compared to 5-ASA users, patients on biologics/JAKi treatment reported higher overall work impairment (coefficient: 0.44, P<0.05). Higher activity impairment was associated with treated UC patients aged 18–39 years, unemployed individuals, and IM/IS users (P<0.05) (Table 3). Additionally, higher WPAI scores were observed across all metrics (P<0.05) (Supplementary Table 3) among patients with ≥ 1 persisting UC symptom compared to those without clinical symptoms.

Table 3.

Multivariate Analyses of WPAI among Treated UC Patients

Bivariate analyses conducted (Supplementary Table 4) were consistent with those from the multivariate regression models (e.g., age, sex, employment status, disease severity and medication adherence) (Table 3). Differences were observed in terms of medication class, where the highest overall work impairment (mean ±SD) was associated with IM/IS (42.3% ± 32.2%), followed by biologics/JAKi (40.5% ± 33.3%), and steroid (33.8% ± 30.3%) users (Supplementary Table 4). Exploratory outcomes for WPAI in those with employment and aged 18–64 years (n = 164) reported a mean ± SD overall work impairment of 30.3% ± 30.0%, with an annual indirect cost of ¥1.1 million. Detailed results are presented in Supplementary Table 5.

3. Overall HRQoL (EQ VAS and SF-36) Outcomes among Treated UC Patients

Multivariate analyses were conducted to examine the factors associated with HRQoL (EQ VAS score, MCS, and PCS scores measured by SF-36v2). Being male, aged 18-39 years, and single were associated with both lower EQ VAS and MCS scores (P<0.05). Additionally, lower educational level, being underweight, former smokers, physical inactivity, mild-to-moderate severity, and ≥ 15 years experiencing UC were associated with lower EQ VAS scores (P<0.05). Unemployment was associated with a lower MCS score, while current smokers were associated with lower PCS scores (P<0.05). Compared with patients treated with 5-ASA monotherapy, IM/IS users had lower EQ VAS and MCS scores, while steroid users had a lower PCS score (P<0.05) (Table 4). Additional analyses on the association between patients with ≥ 1 persisting UC symptom compared to those without clinical symptoms (Supplementary Table 3) revealed lower HRQoL scores (EQ VAS, MCS, and PCS; P<0.05).

Table 4.

Multivariate Analyses of HRQoL among Treated UC Patients

Bivariate analyses conducted (Supplementary Table 6) were consistent with the multivariate regression models (e.g., disease severity, sex, and age) (Table 4). Differences were observed in medication class where the lowest EQ VAS score (59.4 ± 26.3) was observed for steroid users, and the lowest PCS (45.3 ± 11.3) scores were observed for IM/IS users (Supplementary Table 6).

DISCUSSION

This study investigated the disease burden and clinical outcomes of treated Japanese UC patients using data from the Japan NHWS database (2017, 2019, and 2021). The findings highlighted that despite active treatment, UC was bothersome to a certain degree, with more than half having reported moderate-to-severe disease severity. Additionally, patients reported impacted HRQoL and loss in work productivity, especially among the employed patients. This was further translated into a mean indirect cost of ¥1.1 million ($10.2 thousand) per patient annually, suggesting a potential financial burden, especially among the lower income patients (< ¥5.0 million, < $45.3 thousand). Our current finding is comparable to a previous study reporting a mean indirect cost of ¥1.6 million ¥ per IBD patient annually [26]. The findings, particularly those related to standard of care treatments, provided valuable insights into how the HRQoL and WPAI of UC patients varied based on currently available treatment, highlighting persisting unmet needs that would need to be addressed.

Multiple studies coincided with the current findings, highlighting the disease impact on the HRQoL among treated patients. The overall HRQoL scores reported in the current study were lower than the mean Japanese healthy population (EQ VAS: 68.1 vs. 77.8) [45], which reinforced the disease burden of UC reported in current and previous studies. This was additionally reflected by the lower MCS scores in UC patients observed in our study compared to the mean general healthy Japanese population (46.3 vs. 52.0) [26]. A previous study in Japan reported poorer HRQoL outcomes, including physical and social functional capabilities, emotional, and mental wellbeing among IBD patients compared to controls [26,46]. Furthermore, increased disease severity was associated with decreased quality of life, similarly reported in our study [10]. The current study, in conjunction with these findings, underscores that despite available UC treatments, there are unmet needs potentially in identifying and the availability of effective treatments based on symptom severity [47,48]. This echoed previous reports where UC patients experienced some form of depression or anxiety, especially with the active form or increased severity of UC [47]. Moreover, patients reported UC controlling their lives rather than them having control of the outcomes.

In the current findings, younger patients (aged 18–39 years) experienced poorer HRQoL. This could potentially be attributed to emotional challenges arising from the unpredictability of the disease, exacerbated by the need to manage symptoms alongside employment or educational responsibilities as observed in IBD patients [49,50]. This contrasts with the elderly or those who may have experienced the disease for a longer period, having established more effective management routines or having come to terms with their condition, thus reporting a higher quality of life [50]. Additionally, younger patients face societal stigma and may be perceived as incapable due to their age. Their HRQoL may be impacted by different life priorities and the potential lack of social support systems due to the self-imposed stigma [51,52]. These challenges highlight the need for more interventions to improve the quality of life among UC patients, especially in the younger population, which is generally when UC initially onsets. Hence, early intervention and optimal care to improve patient’s quality of life is warranted. This may include psychological adaptation and tailored healthcare that aligns with individual expectations of health and well-being [53,54]. The situation underscores the importance of developing better treatment options to meet the diverse needs of UC patients.

Our study reported that the majority of employed patients experienced WPAI despite treatment, similar to findings from the Japanese cohort of the UC Narrative Global Survey, that reported 80% of employed patients were impacted by UC due to the necessity of taking time off work for treatment or resulting disease symptoms, and close to a half failing to communicate their conditions to employers in fear of repercussions [55]. A previous report highlighted that close to half of the study population felt the negative impacts of IBD on their career path, advancement opportunities, and potential earnings, with more than a third having reported losing their job or resigning due to IBD [22]. Additionally, similar to our findings, it is noteworthy that work productivity impairment has been reported due to UC and its associated symptoms despite treatment, including among patients with mild severity [47]. This once again implicates the importance of innovative treatments that could target difficult-to-treat patients, providing an early and sustainable clinical remission, and underscores the importance of workplace accommodations and understanding from employers to lift the disease burden of UC patients. In addition, patients themselves should be proactive in allowing the society to understand about their disease and obtaining understanding from their employers.

The loss of work productivity has been inevitably associated with financial and societal costs [47]. Productivity impairment at the workplace due to UC was estimated at one-fifth of the mean household income (¥5.0 million, $45.3 thousand, indirect cost at ¥1.1 million) in the current study. This coincided with our study that reported higher WPAI among those with a lower mean household income. Despite available financial assistance for intractable disease, approximately ¥10.0–20.0 thousand per month of co-pay was estimated in Japanese UC patients, implying a higher work productivity impairment impacting the lower income group [56]. Previous studies reported annual indirect costs at approximately 1.5-fold higher for patients with IBD compared to controls [57], while another reported annual indirect costs amounting to ¥1.6 million [26]. Similar trends in recent years were reported in a U.S. and Europe study, with UC reported as being a burdensome disease and impacting the overall work productivity, resulting in higher indirect costs [58,59]. Previous studies have shown associations between increased symptom severity and reduced social support that predisposed increased stress, resulting in the impact on work productivity and financial difficulties [47,60]. However, there is lack of information pertaining to low socioeconomic impact on WPAI among Japanese UC patients and future studies would require further analysis to determine possible associations.

The current study findings reported poorer WPAI and HRQoL scores in patients with lower medication adherence. Many patients were on more than one UC medication, suggesting the potential need for combination therapy in achieving clinical response. Yet, the possibility of combinatory approaches hindering better adherence, preventing patients from receiving the optimal treatment outcomes have been reported [61]. Treatment adherence remains one of the important factors to be addressed among UC patients. Patients with reduced treatment adherence had twice the higher risk for relapse compared to patients with higher treatment adherence, potentially leading to a higher WPAI as a result of increased symptom severity and burden from changing medication [57]. The poor persistence to medication, reflective of suboptimal patient outcomes, could contribute to an increased burden on UC patients and the healthcare system.62,63 Furthermore, non-compliance to treatment are often multifactorial and may include reasons such as, avoidance of injections, medication load, adverse events, fear of adverse outcomes or immunosuppression and therefore requires addressing in order to improve treatment outcomes [46,64,65]. There is a need to investigate the impact of different interventions (e.g., frequency of taking medication, route of administration, number of oral treatments to obtain the necessary therapeutic dosage) leading to non-adherence [66] and introduction of new treatment that could improve adherence would be critical.

The strength of the current findings is that this is one of the very few real-world evidence-based studies assessing the unmet needs of UC treated Japanese patients from various aspects (e.g., employment status, medication types and adherence, and disease severity) and the impact on the HRQoL and WPAI based on the updated NHWS. The NHWS has been utilized in understanding the impact of a disease on individuals and financial and health resources [67-69]. Existing self-administered surveys, targeting large populations with various diseases are rare, therefore the results of the database are unique, and the current study included data that provided a good representation of the study population. This provides insights into how best to utilize available resources and select from potential emerging treatments, helping define treatment approaches for optimal benefits among Japanese UC patients. This is also one of the first studies conducted within the UC Japanese population measuring mean indirect cost due to high work productivity impairment. The recruited study population also reflected a good generalization as majority of UC patients were males, employed, and in their 40s [8] and potentially linked to the current demographic landscape of Japan [70]. The majority of patients in the study utilized conventional therapy, widely accepted by healthcare professionals, with 5-ASA monotherapy being the most prevalent treatment. This aligns with the recommendation of 5-ASA as the first-line therapy for mild-to-moderate UC as outlined in the Japanese IBD guidelines and is consistent with findings from other studies [4,71]. Hence, further supporting the generalizability of the study that is reflective of the current treatment among the Japanese UC patient population. However, this study has limitations. First, the current study results interpretation is constrained as the cross-sectional design restricts interpretations of a causal relationship between disease exposure and health outcomes. Secondly, as this was an online-based study, wherein only individuals with access and knowledge to the internet or better socioeconomic status were involved, it was not representative of the national population [72]. Furthermore, the small number of patients in certain groups may require careful consideration when interpreting the results. However, this was partially mitigated by the involvement of a clinical advisor to support the findings in such circumstances. Additionally, the self-reporting nature of this study presents with recall and self-presentation biases. Despite this, a consistent trend of results was observed, mitigating the self-reporting nature and standardized recruitment process. Moreover, the NHWS lacks an IBD-specific PRO index that limits the accuracy of disease quantification based on numerous activity indices. However, additional insights were obtained through specific UC questions (e.g., persisting UC symptoms, medication adherence and bothersome scale). Finally, it was possible that an increased likelihood of treated UC patients with significant declines in HRQoL responded to the survey, potentially leading to overrepresentation. However, the potential biasness was minimized by the employment of stratified random sampling within the survey population to ensure a true representation of the general adult Japanese population. Additionally, the findings obtained from the current study was consistent with multiple previous findings characterizing the patient-reported burden of UC in the Japanese population.

In summary, the current study highlights that despite currently available treatments a high disease burden and unmet needs affecting Japanese UC patients persist. The majority of patients reported the disease as bothersome with various persisting symptoms. The overall HRQoL scores were lower in comparison to the mean healthy Japanese population. A decrease in HRQoL was associated with patients experiencing moderate-to-severe disease severity and having the disease for ≥ 15 years, with > 30% experiencing anxiety or depression. The indirect cost due to work productivity impairment was high, amounting to approximately a fifth of the mean household income. Furthermore, the association between low treatment adherence and increased WPAI suggests the importance of new and early convenient treatments for optimizing UC outcomes. Additionally, workplace accommodations and understanding of employers and associates on UC could assist in improving work productivity among these patients.

Supplementary Material

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