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Table of Contents

    Topic review

    Quality of Life and IBD

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    Definition

    Inflammatory bowel diseases (IBDs) are chronic disabling conditions, characterized by an unpredictable course with flare-ups and periods of remission, that frequently affect young people and require lifelong medical follow-up and treatment. For years, the main endpoints of IBD treatment had been clinical remission and response, followed by biomarker normalization and mucosal healing. In the last decades, different therapies have been proved to be effective to treat IBD and the use of patient reported outcome (PRO) have become more relevant. Therefore, health-related quality of life (HRQoL) that has been defined as the value assigned to the duration of life influenced by physical and mental health, has been suggested as an important endpoint for IBD management since multiple studies have shown that IBD impairs it, both physically and psychologically. 

    1. Introduction

    Traditional medicine was focused on the physical side of the illness and death rates and life expectancy were the main measures used to evaluate people’s health. This excludes the fact that, in most diseases, the state of health is deeply influenced by mood, coping mechanisms to different situations and social support. The higher prevalence of chronic conditions, as a consequence of the decline of infectious diseases, as well as the development of new technologies that reduced pain, have made necessary newer and more sensitive outcomes beyond morbidity and biological functioning [1]. Quality of life (QoL) has been considered as a component of health since 1947 when the World Health Organization (WHO) began to define health not only as the absence of disease, but also as a state of physical, mental and social well-being [2]. Health-related quality of life (HRQoL) has been defined as the value assigned to the duration of life influenced by health, which is modified by impairments, functional state, perceptions and opportunities that are in turn influenced by diseases, injury and treatments [3]. HRQoL only includes components that are part of an individual’s health and, therefore, excludes other aspects of QoL, as political or economic factors [4].
    Inflammatory bowel diseases (IBD) are chronic, progressive and disabling conditions affecting young people that have a negative impact on their HRQoL [5]. For years, the main endpoints of IBD treatment had been clinical remission and response. Afterwards, new targets like biomarkers and mucosal healing have been introduced in new drug evaluations and, in the last decades, the use of patient-reported outcome (PRO) has also become especially important. In 2015 the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for IBD to be used for a “treat-to-target” clinical management strategy using an evidence-based expert consensus process. In these first recommendations, improvement of HRQoL was only suggested as part of PRO [6]. In the recently published STRIDE II consensus, HRQoL has more weight and it is recommended as an important endpoint for IBD management [7].

    2. How Can We Measure HRQoL in IBD?

    There are two main types of HRQoL tools to evaluate patients with IBD: disease-specific and generic. Disease-specific tools evaluate symptoms and compare the effect of different treatments, while generic tools allow for comparisons between different population and illnesses.
    It is important to take into account two psychometric considerations for choosing which instrument to measure HRQoL:
    • − Reliability is the probability that a questionnaire will perform its intended function adequately. A reliable measure is one that provides consistent and accurate information.
    • − Validity is how accurately a method measures what it is intended to measure. A tool is valid when it measures the characteristic that it claims to measure.
    Plenty of IBD-specific HRQoL tools have been developed and validated for IBD patients [8]. Nevertheless, the majority of these instruments have had no patient involvement in their development [9]. In Table 1, we summarize the main characteristics of the most widely used tools and some other options designed for specific IBD cohorts.
    Table 1. Characteristics of tools for measure HRQoL in IBD.
     

    Target

    Recall Period

    Number of Items

    Response

    Options

    Range of Scores (Worst-Best)

    Reliability

    Specific-disease tools

    IBDQ-32

    IBD

    2 weeks

    32

    7-Level Likert (1–7)

    32–224

    +++

    SIBDQ

    IBD

    2 weeks

    10

    7-Level Likert (1–7)

    10–70

    ++

    IBDQ-36

    IBD

    2 weeks

    36

    7-Level Likert (1–7)

    36–252

    NA

    IBDQ-9

    IBD

    2 weeks

    9

    7-Level Likert (1–7)

    0–100

    ++

    CUCQ-8

    IBD

    2 weeks

    8

    4-Level Likert (0–3) or ordinal format (0–14)

    90–0

    +++

    CLIQ

    CD

    Today

    27

    True/Not true (1–0)

    27–0

    +++

    IBDQ-D

    UC-IPAA

    2 weeks

    32

    7-Level Likert (1–7)

    32–224

    NA

    CAF-QoL

    CD

    6–8 weeks

    28

    4-Level Likert (0–4)

    112–0

    +++

    Generic tools

    SF-36

    Patients and general population

    4 weeks

    36

    Linear transformation of raw scores

    0–100

    +++

    EQ-5D

    Patients and general population

    Today

    6

    • − 3-Likert (1–3)

    • − 5-Likert (1–5)

    • − visual analogue scale

    243 health status, index 0–1

    • − 0–100

    +++

    + Poor, ++ Fair, +++ Good.
    The Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32) and Inflammatory Bowel Disease Questionnaire 36 (IBDQ-36) are the most commonly used [10]. IBDQ-32 is a 32-item questionnaire that has been demonstrated to be reliable and valid. It includes four aspects of the patients’ life and the main domains are intestinal symptoms (10 items), systemic symptoms (five items), social (12 items) and emotional domains (five items). Häuser et al. conducted a validation study of the German version of the IBDQ (IBDQ-D) for patients with ileal pouch anal anastomosis (IPAA) for UC, and they observed that it was a reliable tool in this setting although it had some limitations in terms of validity [11]. The short version of IBDQ-32 is the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). SIBDQ also contains symptom, social and emotional sections. IBDQ-36 is a 36-item questionnaire that has also been proven to be valid and reliable. It comprises the following points: intestinal symptoms (eight items), systemic symptoms (seven items), social (6 items) and emotional domains (eight items), and functional impairment (seven items). The short version of IBDQ-36 is IBDQ9. IBDQ9 only contains one domain (total score) and the comprehensiveness is lower than IBDQ-36 [9].
    Another tool, Crohn’s Life Impact Questionnaire (CLIQ), composed of 27 dichotomous items, is focused on how the impairments affect need fulfilment. It has demonstrated good validity and reproducibility, and it is easy to complete in a few minutes [12]. Recently, the Crohn’s Anal Fistula Quality of Life (CAF-QoL) has been developed to evaluate the impact of anal fistula. It is a new PRO measure for Crohn’s perianal fistula that has been validated. CAF-QoL is a 28-item questionnaire that has demonstrated to be internally consistent, reliable, stable and valid [13]. Among them, the best questionnaires related to relevance, comprehensiveness and comprehensibility are IBDQ-32 and CLIQ. In Table 1, we summarize the main characteristics of the most widely questionnaires used.
    Other examples of disease-specific instruments are the Crohn’s and Ulcerative Colitis Questionnaire (CUCQ), Inflammatory Bowel Disease Questionnaire 30 (IBDQ-30), Norwegian Inflammatory Bowel Disease Questionnaire (IBDQ-N), Cleveland Global Quality of Life (CGQL), Short Health Scale (SHS), Edinburgh Inflammatory Bowel Disease Questionnaire (EIBDQ), short Inflammatory Bowel Disease Questionnaire 10 (sIBDQ-10) and Inflammatory Bowel Disease Disability Index (IBD-DI). In paediatric IBD patients, the IMPACT series tools (IMPACT, IMPCT-II and IMPACT III) were used to evaluate the HRQoL. IMPACT was proven to be valid and contains 4 domains: symptoms, physical, emotional and social domains [8][14].
    The generic questionnaires most commonly used are the Generic 36-item Short Form Survey (SF-36) and The EuroQoL–dimension (EQ-5D). SF-36 was developed in the USA for use in the Medical Outcomes Study (MOS). It is a generic scale that provides quantitative information related to HRQoL and has good validity and reliability. It is frequently reported as two separate figures, a physical component score (PCS) and a mental component score (MCS), which included a total of 36 items allocated in eight domains: physical functioning (10 items), role physical (four items), social functioning (two items), bodily pain (two items), mental health (five items), role emotional (three items), general health perceptions (five items) and one item about general health [15]. EQ-5D is a generic, reliable and valid instrument developed by the EuroQoL group. It can be used to assess HRQoL but also the cost-utility analysis of health care interventions [16]. Other similar instruments can be World Health Organization Quality of Life (WHOQOL)-BREF, Short Form SF-12, Satisfaction with Life Scale (SWLS), EORTC Quality of Life Questionnaire C-30, Quality of Well Being Scale or Health Utilities Index [17][18]. In paediatrics, the generic tools more widely used are PedsQ1, Child Health Questionnaire (CHQ), KINDL, KINSCREEN 27, DISABKIDS HRQOL [19].

    3. Quality of Life Studies in UC

    To date, multiple studies have reported that UC impairs QoL, which can also be affected by demographic, psychological and socioeconomic factors [20][21]. Clinical activity was pointed out as the factor with the most negative impact in HRQoL [22], although it has been shown that it’s still compromised during quiescent disease as compared to the general population [23]. Rasmussen et al. observed that bowel frequency, urgency and rectal bleeding are the symptoms that most significantly affect these patients’ HRQoL [24]. Apart from the physical symptoms, IBD patients complain about an important emotional burden which is barely addressed during follow-up appointments [25][26]. Different therapies have been proved to be effective to treat UC and improve the HRQoL of those who suffer from it (Table 2) although its administration schedules and side effects can also negatively affect HRQoL.
    Table 2. IBD treatments that have been shown to improve HRQoL.

    Treatment

    Study

    Measurement Tool(s)

    No. Patients

    HRQoL: Primary Outcome

    Results

    5-ASA

    Robinson et al. [27]

    5 disease-specific and 7 general items

    374 UC

    Yes

    Mesalamine 2 g and 4 g daily was significantly superior to placebo in improving each of the 12 HRQoL parameters.

    Probert et al. [28]

    EQ-5D-3L

    115 UC

    No

    The combined (oral + rectal) therapy group reported a significant improvement in the ‘mobility’, ‘usual activity’ and ‘anxiety/depression’ domains at week 4.

    Thiopurines

    Alruthia et al. [29]

    EQ-5D-3L

    EQ-5D-VAS

    160 IBD (56% CD, 44% UC)

    Yes

    Patients on AZA presented higher HRQoL at six-month follow-up compared with patients on other treatments (β = 9.35; 95% CI: 0.486–18.22; p = 0.003).

    Bastida et al. [30]

    SF-36

    IBDQ

    92 IBD (68 CD, 24 UC)

    Yes

    Compared with baseline, 68 and 64% patients’ scores improved at 6 and 12 months, respectively (ΔIBDQ was 0.86 and 1.05, respectively). SF-36 showed a similar improvement.

    Calvet et al. [31]

    SF-36

    33 RCD a, 14 ACD b,

    66 HC c

    Yes

    SF-36 were 85 in RCD, 85 in HC (p = 1), and 58.6 in ACD (p < 0.001 for comparison with RCD and HC).

    Infliximab

    Feagan et al. [32]

    IBDQ

    SF-36

    728 UC

    No

    IBDQ score improvement was significantly greater in the IFX 5 and 10 mg/kg groups (40 and 36, respectively p < 0.001) vs. placebo (28).

    Silva et al. [33]

    IBDQ

    31 UC

    Yes

    In IFX group (n = 21), the IBDQ scores ranges from 116.2 at baseline to 170.75 and 176.62 at week 30 and 54, respectively (p ≤ 0.02)

    Feagan et al. [34]

    IBDQ

    SF-36

    335 CD

    No

    The mean change in the IBDQ at week 54 compared to baseline was 22.1 in the 5 mg/kg and 30.2 in 10 mg/kg IFX maintenance group while it was 8.9 in the placebo group (p ≤ 0.05). SF-36 changed in the same line.

    Adalimumab

    Travis et al. [35]

    SIBDQ

    EQ-5D-5L

    EQ-5D-VAS

    463 UC

    Yes

    Significant improvements from baseline to week 26 were detected on SIBDQ (mean change 17.4) and EQ5D (index: 0.1 ± 0.2; VAS: 19.5).

    Louis et al. [36]

    SIBDQ

    945 CD

    No

    60% of IFX-naïve patients and 47% of IFX primary non-responders reported clinically significant improvements (≥9 points) on SIBDQ.

    Saro et al. [37]

    IBDQ

    EQ-5D

    EQ-5D-VAS

    126 CD

    Yes

    It has been shown a significant improvement on the EQ5D from 0.735 to 0.797, the EQ5D VAS from 50.0 to 80.0, and the IBDQ from 56.7 to 67.5 (p < 0.05 for all comparisons).

    Golimumab

    Feagan et al. [38]

    IBDQ

    SF-36

    1064 UC

    No

    It was determined a significantly greater improvement from baseline to week 6 in GLM vs. placebo groups in IBDQ (27.2 vs. 14.6), SF-36 PCS (4.14 vs. 2.46) and MCS (4.89 vs. 1.60, p < 0.01 for all comparisons).

    Vedolizumab

    Feagan et al. [39]

    IBDQ

    SF-36

    EQ-5D-3L ED-5D-VAS

    373 UC

    No

    Patients on VDZ reported significantly greater improvements in IBDQ and EQ5D-VAS scores. For EQ-5D utility score, only the VDZ every 4 weeks group showed a significant difference from placebo. At week 52, more patients on VDZ met the minimal clinically meaningful difference thresholds for IBDQ, SF-36 physical component and EQ5D-VAS scores.

    Loftus et al. [40]

    IBDQ

    769 UC (383 VDZ, 386 ADA)

    No

    At week 52, clinically important IBDQ improvement was detected in a greater proportion of VDZ treated patients compared with ADA treated ones (52.0% vs. 42.2%). Likewise, 50.1% (VDZ) vs. 40.4% (ADA) of patients achieved IBDQ remission.

    Vermiere et al. [41]

    IBDQ

    EQ5D-VAS

    SF-36

    1349 CD

    No

    At week 80, the mean changes from baseline HRQL scores were >51 for IBDQ, >23 for EQ-5D VAS, >9 for SF-36 PCS and >10 for SF-36 MCS.

    Parkes et al. [42]

    SIBDQ

    61 IBD

    (21 CD, 40 UC)

    No

    SIBDQ score increased by 8.5 and 10.2 points in CD and UC patients, respectively, at week 14.

    Eriksson et al. [43]

    SHS

    169 CD

    No

    It has been seen a significant decreased of the SHS score at week 52 (n = 68; p < 0.001)

    Ustekinumab

    Sandborn et al. [44]

    IBDQ

    SF-36

    284 UC

    No

    55.6% of patients who had been treated with USK were in IBDQ remission. Regarding the SF-36, 50.0% and 45.1% of patients had a clinically meaningful improvement in the PCS and the MCS, respectively.

    Sands et al. [45]

    IBDQ

    SF-36

    1368 CD

    No

    A clinically meaningful improvement in IBDQ score at week 8 was achieved in 68.1% of anti-TNF naïve patients and 54.8% of patients with previous failure to antiTNF. Similarly, greater improvements in SF-36 in the USK group have been determined.

    Marquès et al. [46]

    IBDQ

    33 CD

    Yes

    18% achieved IBDQ normalization at week 52.

    Tofacitinib

    Panés et al. [47]

    IBDQ

    SF-36

    1161 UC (induction)

    593 UC (sustain)

    No

    In OCTAVE induction 1 and 2, mean IBDQ changes from baseline to week 8 was 40.7 and 44.6 with TFC 10mg twice daily versus 21 and 25 with placebo, respectively (p < 0.001). Mean SF-36 changes were comparable with the IBDQ changes and both were sustained at week 52

    Surgery (intestinal resection)

    Wright et al. [48]

    IBDQ

    SF-36

    174 CD

    No

    A significant improvement has been observed at 6 months postoperatively compared to preoperatively in PCS (68 vs. 40), MCS (68 vs. 44) and IBDQ (171 vs. 125; p < 0.001 for all comparisons).

    Ha et al. [49]

    5 generic tools

    3 disease-specific tools

    1108 CD

    Yes

    Both generic and disease-specific tools showed an improvement in HRQoL from 2 weeks after intestinal resection for up to 5 years.

    AZA: azathioprine. IFX: infliximab. GLM: golimumab. VDZ: vedolizumab. ADA: adalimumab. USK: ustekinumab. TFC: tofacitinib.a Remission Crohn’s disease. b Active Crohn’s disease. c Healthy controls.

    4. Quality of Life Studies in CD

    There are several studies that have shown an association between CD and significant disability and impaired HRQoL. There is a systematic review and meta-analysis that compared HRQoL between CD and UC including physical (2375 participants) and mental scores (2664 participants). The HRQoL scores were shown to be lower in patients with CD compared with UC, but these differences were borderline significant [50].
    In the systematic review of Van der Have et al. including 5735 patients with CD, the HRQoL was consistently impaired by the occupational disability, number of flares, disease activity, need for hospital admission and use of corticosteroids. Furthermore, the biological treatment had a beneficial impact in the HRQoL. The majority of the studies included in this review employed both generic and disease-specific HRQoL measures, the IBDQ and the SF-36 being the most commonly used [51].
    Despite the thinking that HRQoL is mainly related with clinical activity in CD, in a study performed in 92 CD patients in remission, scores on the SF-36 were lower than in the general population of similar age and sex. Age, colonic location and previous surgery was related with worse HRQoL [52].
    The effectiveness of different treatments improving HRQoL in patients with CD has been evaluated in clinical trials of new drugs, but also real-life studies (Table 2). Only a few studies have been conducted to assess the impact of thiopurines in HRQoL. A prospective study that included 92 IBD patients (68 CD) who started thiopurines showed a significant impairment HRQoL at week 0 with a basal median IBDQ score of 4.99 (range 2.37–6.84) as compared to patients in remission. In the first year after starting treatment, all dimensions of the IBDQ demonstrate a statistically significant improvement that was more pronounced in those patients receiving steroids at the beginning of the study [30]. In a case-control study it was shown a restoration of HRQoL in patients with CD in remission under thiopurines without differences with healthy controls [31].

    The entry is from 10.3390/ijerph18137159

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