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Gastroenterology and hepatology
Protocol
Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study
  1. Laura Janssen1,2,
  2. Reinier Cornelis Anthonius van Linschoten3,4,
  3. Rachel Louise West5,
  4. Lennard P L Gilissen6,
  5. Mariëlle Romberg-Camps7,
  6. Lloyd Brandts8,
  7. Zlatan Mujagic1,9,
  8. Tessa EH Römkens10,
  9. M Pierik1,11
  1. 1NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Limburg, Netherlands
  2. 2Gastroenterology and Hepatology, Maastricht UMC+, Maastricht, Netherlands
  3. 3Gastroenterology and Hepatology, Franciscus Gasthuis en Vlietland, Rotterdam, Netherlands
  4. 4Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands
  5. 5Department of Gastroenterology & Hepatology, Franciscus Gasthuis, Rotterdam, Zuid-Holland, Netherlands
  6. 6Department of Gastroenterology, Catharina Hospital, Eindhoven, North Brabant, Netherlands
  7. 7Gastroenterology, Zuyderland Medical Centre Sittard-Geleen, Sittard-Geleen, Limburg, Netherlands
  8. 8Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht UMC+, Maastricht, Limburg, Netherlands
  9. 9Division of Gastroenterology-Hepatology, Maastricht University Medical Centre+, Maastricht, Limburg, Netherlands
  10. 10Department of Gastroenteroloy and Hepatology, Jeroen Bosch Hospital, 's-Hertogenbosch, Noord-Brabant, Netherlands
  11. 11Department of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, Limburg, Netherlands
  1. Correspondence to Laura Janssen; laura.janssen{at}maastrichtuniversity.nl

Abstract

Introduction Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier for better disease control. We aim to validate and recalibrate commonly used patient-reported symptom scores combined with a faecal calprotectin (FC) home test as non-invasive diagnostic tool for remote monitoring of IBD, both in daily practice and in a strict trial setting. Endoscopy will be used as the gold standard.

Methods and analysis In this multicentre prospective validation study, adult IBD patients are asked to fill out questionnaires regarding disease activity (Monitor IBD At Home, mobile Health Index, Manitoba IBD Index, IBD control and patient-HBI/patient-Simple Clinical Colitis Activity Index), perform a FC home test and collect a stool sample for routine laboratory FC measurement, before the start of the bowel preparation for the ileocolonoscopy. Endoscopic disease activity will be scored according to the simplified endoscopic score for Crohn’s disease (CD) for CD patients or Ulcerative Colitis Endoscopic Index for Severity and Mayo Endoscopic Subscore for ulcerative colitis patients. The main study outcome is the diagnostic test accuracy of the various patient-reported scores to assess mucosal inflammation in combination with a FC home test.

Ethics and dissemination This study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 03 March 2021 (METC 20–085) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.

Trial registration number NCT05886322

  • Inflammatory bowel disease
  • Adult gastroenterology
  • Statistics and research methods
  • Endoscopy
  • Patient-reported outcome measures
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2023-076290

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    STRENGTHS AND LIMITATIONS OF THIS STUDY

    • This is the first direct comparison of multiple patient-reported outcome measures (PROMs) combined with a faecal calprotectin (FC) home test, using the gold standard ileocolonoscopy as a reference.

    • The difference between daily clinical practice and strict trial setting is taken into account in the cut-offs of the endoscopic scores defining mucosal inflammation.

    • A limitation of this study is that the recalibrated PROMs are not externally validated.

    • A limitation of this study is the probability of intraindividual variability in FC testing.

    Introduction

    Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases characterised by a relapsing-remitting course and together are referred to as inflammatory bowel disease (IBD). Up to 0.5% of the general population in the Western World are diagnosed with IBD,1 and the prevalence continues to rise.2 3 The growing prevalence, lack of curative treatment and early onset in life lead to a large impact of IBD on healthcare systems4 and patients’ quality of life.5

    Recurrent mucosal inflammation or chronic subclinical inflammation can lead to irreversible bowel damage.6 7 Monitoring of IBD is aimed at early recognition of mucosal inflammation, so treatment can be optimised to prevent disease progression.8 Ileocolonoscopy remains the gold standard to evaluate mucosal inflammation.9 During endoscopy, inflammation can be quantified using various scores, such as the simplified endoscopic score for CD (SES-CD)10 or the Ulcerative Colitis Endoscopic Index for Severity (UCEIS)11 and Mayo Endoscopic Subscore (MES) for UC. However, ileocolonoscopy is an invasive, time-consuming, expensive and potentially harmful procedure and thus not suitable for frequent monitoring.

    The ideal monitoring test is non-invasive, affordable, simple to conduct and detects (imminent) disease activity. Moreover, it should be suitable for remote monitoring, since visits to the outpatient department are time-consuming and burdensome for both patients and healthcare providers when patients are in stable comprehensive remission, based on objective measures of disease activity and patient-reported outcome measures (PROMs).12 Remote monitoring might reduce strain on healthcare systems13 and reduce potential harm for immunocompromised patients, such as during the COVID-19 pandemic.

    Several clinical disease activity indices have been developed. Classic symptom-based scores such as the Crohn’s disease activity index, Harvey Bradshaw Index (HBI) and Simple Clinical Colitis Activity Index (SCCAI) were initially validated against physician global assessment and have been found to correlate poorly with endoscopic disease activity.14 15 These scores are clinician-reported and include data from physical examination and/or laboratory test, and are not suitable for remote monitoring. PROMs that can be used for remote monitoring are the Monitor IBD At Home (MIAH) score,16 mobile Health Index (mHI),17 patient-HBI18 and patient-SCCAI.19 These PROMs measure self-reported disease activity based on indicators that are important to physicians.20 In monitoring of IBD, assessment of subjective disease control might provide additional valuable information, since a perception gap between physicians and patients concerning disease activity frequently occurs, and subjective perceived control is associated with quality of life.21 For this, the IBD-control22 and Manitoba IBD Index (MIBDI)23 can be used, since these represent outcomes that matter most to IBD patients and were developed and validated according to the guidelines of the Food and Drug Administration and Oxford Patient-Reported Outcome Measurement group but were not tested relative to endoscopy. Of the other PROMs, the MIAH score and mHI were validated against endoscopy, but the validity of the other PROMs to predict mucosal inflammation remains unclear.

    However, monitoring disease activity based on symptoms alone is insufficient as ongoing mucosal inflammation can be present in the absence of symptoms, while, on the other hand, symptoms can persist when mucosal healing is reached.16 24 Objective markers, such as faecal calprotectin (FC), are used as a proxy for endoscopy to monitor mucosal inflammation. FC reduction to an acceptable range has been added as a treatment target in the Selecting Therapeutic Targets in Inflammatory Bowel Disease-II recommendations.8 In the hospital, FC is determined with an ELISA. This measurement is time-consuming and requires a high level of expertise. In the last years, FC home tests have been developed. FC home tests are cheaper, easier to perform, safe and suitable for remote monitoring.

    The combination of a PROM and a FC home test might be the ideal way to non-invasively detect mucosal inflammation in IBD patients. With adequate screening for mucosal inflammation, endoscopies can be prevented and treatment can be timely optimised for better disease control. In this study, we aim to validate various PROMs combined with a FC home test for the detection of mucosal inflammation, relative to the gold standard endoscopy, both in daily clinical practice and in a strict trial setting.

    Methods and analysis

    Study aim

    The main objectives of this study are to:

    • Assess which PROM, with and without FC home test, best predicts mucosal inflammation, compared against the gold standard ileocolonoscopy.

    • Recalibrate PROMs, that is, to identify the optimal cut-off values, with the FC home test to optimise prediction of mucosal inflammation, relative to the gold standard ileocolonoscopy.

    The secondary objectives are to:

    • Assess which PROM, with and without FC home test, best predicts mucosal inflammation in a strict trial setting, relative to the gold standard ileocolonoscopy.

    • Recalibrate PROMs with the FC home test to optimise prediction of mucosal inflammation in a strict trial setting, relative to the gold standard ileocolonoscopy.

    • Assess the association between histologic disease activity and self-assessment of IBD disease control and abdominal pain in IBD patients in (clinical and) endoscopic remission.

    • Assess agreement between FC levels measured by FC home tests and by routine laboratory tests in the participating centres.

    Study design

    This is a multicentre prospective cohort study conducted in Maastricht University Medical Centre+ (MUMC+), Jeroen Bosch Hospital (JBH), Franciscus Gasthuis & Vlietland (FGV), Catharina Hospital Eindhoven (CHE) and Zuyderland Medical Centre (ZMC) in the Netherlands. The Standard Protocol Items: Recommendations for Interventional Trials checklist was followed (see online supplemental file 1).

    Study population

    Adult patients with an established diagnosis of CD or UC are eligible for participation if they are scheduled for an ileocolonoscopy or sigmoidoscopy (the latter only for UC) as part of routine care at the endoscopy ward of one of the participating centres and meet all of the following inclusion criteria:

    • Established diagnosis of CD or UC according to the ECCO guidelines.9

    • CD or UC patients scheduled for an ileocolonoscopy or UC patients scheduled for a sigmoidoscopy at the endoscopy ward of one of the participating centres (regardless of indication)

    • Aged 18 years or older

    • Smartphone with internet access (for use of FC home test).

    Patients will be excluded if they meet any of the following criteria:

    • Unclassified IBD

    • Ileostomy, colostomy, ileoanal pouch anastomosis or ileorectal anastomosis

    • Isolated upper gastrointestinal CD or isolated perianal disease

    • Insufficient knowledge of Dutch language.

    Recruitment of patients started in June 2022 in MUMC+, in October 2022 in JBH and FGV, and is expected to start in May 2024 in CZE and ZMC. The first patient was included in MUMC+ on 7 June 2022. At the time of submission (2 June 2023), we have included 113 patients, and full inclusion is expected in June 2025.

    Outcomes

    The primary outcome is the predictive value of different PROMs, with and without FC home test, for identifying mucosal inflammation in daily clinical practice, defined as an SES-CD >6 for CD, and MES ≥2 or UCEIS >4 for UC or ulcers >0.5 cm for both. For the secondary outcome of mucosal inflammation in a strict trial setting, the cut-offs are, respectively, an SES-CD >2 for CD and UCEIS >1 or MES ≥1 for UC (table 1). The PROM that provides the highest net benefit in decision curve analysis (see below) is deemed best. If biopsies are taken, the association between clinical symptoms, subjective disease control and histologic disease activity score will be assessed in patients in endoscopic remission. Additionally, the agreement between the FC levels measured by the home test and by the laboratory test will be assessed.

    View this table:
    Table 1

    Cut-off values to determine the presence of mucosal inflammation

    Predictors

    The PROMs used in this study are the MIAH score, mHI, MIBDI, IBD-control, and the patient-reported HBI and SCCAI. The MIAH score and mHI are validated against endoscopy, whereas the other PROMs have only been validated against conventional clinical disease outcomes. See table 1 for the previously published cut-offs for the PROMs and FC that will be used to predict mucosal inflammation in the clinical practice and strict trial settings.16–19 22 23 Moreover, the questions on stool frequency and rectal bleeding for UC patients, and stool frequency and abdominal pain for CD patients, will be used to determine disease activity according to the patient-reported outcome (PRO-2).

    Study procedures

    Eligible IBD patients will be invited to participate in this study at the IBD outpatient department or with an invitation letter. After signing an informed consent form, patients will receive one FC home test, one faecal container with a spatula and a link to the online questionnaires. Patients are asked to fill out the PROMs, perform the FC home test and collect a faecal sample 1 to 2 days before they start bowel preparation for endoscopy. Basic demographic and disease-specific data are collected at the time of colonoscopy.

    Before the start of the bowel preparation, all patients fill out online questionnaires via Castor, consisting of the MIAH, mHI, p-HBI for CD or p-SCCAI for UC, IBD-control and MIBDI. In addition, the Bristol stool chart and questions regarding the ease of use of the FC home test are completed.

    FC is measured by SmarTest (Preventis, Germany) and by routine laboratory test. SmarTest is a FC immunological test combined with a smartphone application. On the same day as filling out the questionnaires, patients will measure FC using a SmarTest home test. Furthermore, patients collect a faecal sample of the same stool for measurement of FC by the local routine laboratory test, that is, by EliA Calprotectin test (Thermo Fisher Scientific) on the Phadia 250 in MUMC+ and FGV, QUANTA Flash Calprotectin (Inova Diagnostics) on BIO FLASH in JBH and DiaSorin LIAISON Calprotectin Assay in ZMC and CHE.

    The ileocolonoscopy used as a reference for mucosal inflammation in this study is part of standard care. Endoscopic activity will be assessed by a central reader per hospital using SES-CD for CD, and MES and UCEIS for UC. The cut-offs used in a strict trial setting are usually too strict for therapeutic decision-making in daily practice. Therefore, we will use pragmatic and strict endoscopic scores in this study, for use in daily clinical practice and in a strict trial setting, respectively. These cut-off values are based on expert opinions and recommendations.8 If biopsies are taken, histologic activity will be scored by a blinded central pathologist according to the Geboes score and the Inflammatory Bowel Disease-Distribution, Chronicity, Activity (IBD-DCA) score.25–27

    Sample size

    For the primary objective of comparing PROMs for the prediction of mucosal inflammation, a power calculation is not appropriate as statistical testing and confidence intervals are not used when comparing decision curves.16 For redeveloping PROMs, we need enough patients in both disease activity groups to estimate all coefficients of the longest PROM without overfitting. Using a rule of thumb, this translates to at least 10 times the number of coefficients for the IBD-control plus a coefficient for FC for a total of 90 patients with mucosal inflammation and 90 patients without, per disease type. Based on this information, we estimated that around 200 CD patients and 200 UC patients are needed, with an estimated prevalence of mucosal inflammation of 30–50%.16 After including 300 patients, we plan to determine the actual prevalence of mucosal inflammation (using the pragmatic daily practice definition) per IBD type, so sample size can be adjusted if necessary.

    Statistical analyses

    Basic demographic and disease-specific data include sex, age, type of IBD, Montreal classification at diagnosis, disease duration, surgical history, current IBD medication, smoking status and the indication for colonoscopy or sigmoidoscopy. Descriptive statistics will be used to display these data. The frequency of categorical variables and the mean with SD or median with IQR of continuous variables will be reported.

    Patients not undergoing their scheduled ileocolonoscopy or when it is not possible to determine the endoscopic disease activity score will be replaced by new subjects. This can occur when bowel preparation is inadequate or when the upper limit of inflammation is not reached during sigmoidoscopy.

    Prediction of mucosal inflammation in daily clinical practice

    The primary outcome is prediction of mucosal inflammation in daily clinical practice, for different PROMs and their cut-offs (table 1), both with and without a FC home test, compared against the gold standard ileocolonoscopy. Of these PROMs, we will assess diagnostic test accuracy (sensitivity, specificity, positive predictive value and negative predictive value), discrimination (c-statistic), calibration (intercept and slope) and net benefit through decision curve analysis.

    Decision curve analysis

    To determine the best PROM for predicting mucosal inflammation on ileocolonoscopy, we will use decision curve analysis.28 This shows the net benefit of each PROM, combining the benefits of diagnosing mucosal inflammation versus the harms of doing an unnecessary colonoscopy, taking into account patient and provider preferences. Net benefit of screening with each PROM will be compared with doing an ileocolonoscopy in all and in no patients. This will be plotted over threshold probabilities of 0 to 50%. The threshold probability can be interpreted as the relative benefit of detecting mucosal inflammation versus the harm of doing an unnecessary colonoscopy. A threshold probability of 1% implies that diagnosing mucosal inflammation is 99 times more beneficial than avoiding a colonoscopy, while a threshold probability of 50% implies that avoiding a colonoscopy is as beneficial as diagnosing mucosal inflammation. In the standard case of decision curve analysis, patients are classified according to their predicted probability of the event and a probability cut-off that is equal to the threshold probability. In our case, however, not all PROMs calculate a predicted probability (IBD-control and MIBDI), while others already have a prespecified cut-off (MHI, MIAH, p-HBI and p-SCCAI). As such, we will use the cut-offs as defined in the literature (table 1) and plot net benefit of using these cut-offs over a range of threshold probabilities. This reflects the way the PROMs are used in clinical practice.

    Redeveloping remote monitoring tool for IBD

    We want to optimise PROMs with and without FC home test for screening for mucosal inflammation in daily clinical practice and in a strict trial setting. For each PROM, we will specify a logistic regression model with mucosal inflammation as the dependent variable in which we re-estimate a coefficient for each question in the PROM and FC if applicable. Penalised maximum likelihood will be used to improve external validity. Gold standard will be mucosal inflammation determined by the UCEIS for UC and SES-CD for CD. We will assess discrimination (c-statistic), calibration (intercept and slope) and clinical benefit (decision curve analysis) of using the recalibrated PROMs for screening of mucosal inflammation. Models will be internally validated using bootstrap optimism correction with 400 bootstrap samples, and optimism-corrected estimates will be reported.

    Prediction of mucosal inflammation in a strict trial setting

    We will determine the best PROM for predicting mucosal inflammation in a strict trial setting, using stricter cut-off values for endoscopic remission (table 1). Decision curve analysis will be used, as described above.

    Association between abdominal pain and histological disease activity

    Abdominal pain is frequently present in IBD patients in endoscopic remission,29 and it is unknown whether this may be caused by mucosal nerve sensitisation due to ongoing low-grade mucosal inflammation (ie, histological activity) even when endoscopic remission is achieved. Therefore, the association between histologic activity and abdominal pain scores in IBD patients in endoscopic remission will be assessed. Abdominal pain will be assessed using the abdominal pain question from the p-HBI for CD and from the MIAH for UC. In addition, the association between histologic activity and poorly controlled IBD (ie, IBD-control <13/ visual analogue scale (VAS) <85) in patients in clinical (according to the PRO-2) and endoscopic remission will be assessed. Moreover, the prevalence of histologic activity in patients in clinical (according to the PRO-2) and endoscopic remission with well-controlled IBD (ie, IBD-control>13/VAS >85) will be assessed.

    Agreement between FC home test and routine laboratory tests

    We will determine the percentage of total agreement between the FC home test and routine laboratory tests to detect mucosal inflammation or remission. FC levels are measured in µg/g, but will, for agreement on mucosal inflammation, be treated as a dichotomous variable based on the predefined cut-off values (table 1). Cohen’s kappa coefficient will be calculated, with the following interpretation: poor (<0), slight (0–0.20), fair (0.21–0.40), moderate (0.41–0.60), substantial (0.61–0.80) and almost perfect (0.81–0.99).

    Additionally, the level of test agreement will be analysed by a Bland-Altman plot, showing the difference against the mean of the paired measurements of the FC home test and the laboratory test. Disagreements in the lower values of the tests (ie, below 500 µg/g) have a bigger impact than disagreements in the higher levels (ie, above 500 µg/g), since these disagreements can lead to misclassification of disease activity more easily.30 The predefined acceptable limits of difference are set at +/−50 µg/g for the lower range (ie, below 500 µg/g) and+/−200 µg/g for the higher range (ie, above 500 µg/g).

    Ethics and dissemination

    The protocol has been approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 3 March 2021 (METC 20–085) and the latest amendment on 27 February 2023. This study will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice (GCP) guidelines and is monitored by the Clinical Trial Centre Maastricht. Approval of the institutional review board of the participating centres has been obtained, and written informed consent will be obtained from all patients.

    All substantial changes to the protocol will be submitted as an amendment to the Medical Research Ethics Committee.

    Publication

    All study results will be published in international peer-reviewed medical journals, regardless of the nature of the outcome. First and last authors will depend on the specific contributions in each manuscript. Site principal investigators will be co-authors. Study results will also be presented at relevant national and international conferences.

    Data deposition and curation

    Data will be coded using consecutive numbers combined with the name of the participating site. A subject identification code list will be used to link the data to the subject. The coordinating investigator, those involved in the execution of the study, research monitors and the Health and Youth Care Inspectorate have access to the source data at the investigator site. This is necessary to make sure the research is correctly performed and reliable. Patient identification log, hospital records, informed consent forms, eCRFs and databases are kept for 15 years after completing the study. The data are always handled confidentially, in accordance with GCP guidelines and the protocol.

    Patient and public involvement

    Patients and public are not involved in recruitment or conduction of the study. The burden of participation was assessed by representatives of patient associations participating in the Medical Research Ethics Committee. In the development of PROMs (p-HBI, p-SCCAI and MIAH), patients were involved to assess the comprehensibility of the questionnaires. To incorporate the patients’ perspective on disease control, we included the IBD-control and MIBDI.

    Ethics statements

    Patient consent for publication

    References

    1. ↵
      1. Kaplan GG
      . The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 2015;12:720–7. doi:10.1038/nrgastro.2015.150
      OpenUrlCrossRefPubMed
    2. ↵
      1. Kaplan GG,
      2. Windsor JW
      . The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2021;18:56–66. doi:10.1038/s41575-020-00360-x
      OpenUrlCrossRefPubMed
    3. ↵
      1. van den Heuvel TRA,
      2. Jeuring SFG,
      3. Zeegers MP, et al
      . A 20-Year Temporal Change Analysis in Incidence, Presenting Phenotype and Mortality, in the Dutch IBDSL Cohort-Can Diagnostic Factors Explain the Increase in IBD Incidence? J Crohns Colitis 2017;11:1169–79. doi:10.1093/ecco-jcc/jjx055
      OpenUrlPubMed
    4. ↵
      1. van Linschoten RCA,
      2. Visser E,
      3. Niehot CD, et al
      . Systematic review: societal cost of illness of inflammatory bowel disease is increasing due to biologics and varies between continents. Aliment Pharmacol Ther 2021;54:234–48. doi:10.1111/apt.16445
      OpenUrlPubMed
    5. ↵
      1. Knowles SR,
      2. Graff LA,
      3. Wilding H, et al
      . Quality of Life in Inflammatory Bowel Disease: A Systematic Review and Meta-analyses—Part I. Inflamm Bowel Dis 2018;24:742–51. doi:10.1093/ibd/izx100
      OpenUrlCrossRefPubMed
    6. ↵
      1. Torres J,
      2. Mehandru S,
      3. Colombel J-F, et al
      . Crohn’s disease. Lancet 2017;389:1741–55. doi:10.1016/S0140-6736(16)31711-1
      OpenUrlCrossRefPubMed
    7. ↵
      1. Ungaro R,
      2. Mehandru S,
      3. Allen PB, et al
      . Ulcerative colitis. Lancet 2017;389:1756–70. doi:10.1016/S0140-6736(16)32126-2
      OpenUrlCrossRefPubMed
    8. ↵
      1. Turner D,
      2. Ricciuto A,
      3. Lewis A, et al
      . STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology 2021;160:1570–83. doi:10.1053/j.gastro.2020.12.031
      OpenUrlCrossRefPubMed
    9. ↵
      1. Maaser C,
      2. Sturm A,
      3. Vavricka SR, et al
      . ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohn's Colitis 2019;13:144–164K. doi:10.1093/ecco-jcc/jjy113
      OpenUrlCrossRefPubMed
    10. ↵
      1. Daperno M,
      2. D’Haens G,
      3. Van Assche G, et al
      . Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc 2004;60:505–12. doi:10.1016/s0016-5107(04)01878-4
      OpenUrlCrossRefPubMed
    11. ↵
      1. Travis SPL,
      2. Schnell D,
      3. Krzeski P, et al
      . Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut 2012;61:535–42. doi:10.1136/gutjnl-2011-300486
      OpenUrlAbstract/FREE Full Text
    12. ↵
      1. Schreiber S,
      2. Feagan BG,
      3. Peyrin-Biroulet L, et al
      . Filgotinib Improved Health-Related Quality of Life and Led to Comprehensive Disease Control in Individuals with Ulcerative Colitis: Data from the SELECTION Trial. J Crohns Colitis 2023;17:863–75. doi:10.1093/ecco-jcc/jjad018
      OpenUrlPubMed
    13. ↵
      1. de Jong MJ,
      2. van der Meulen-de Jong AE,
      3. Romberg-Camps MJ, et al
      . Telemedicine for management of inflammatory bowel disease (myIBDcoach): a pragmatic, multicentre, randomised controlled trial. Lancet 2017;390:959–68. doi:10.1016/S0140-6736(17)31327-2
      OpenUrlPubMed
    14. ↵
      1. Brand EC,
      2. Elias SG,
      3. Minderhoud IM, et al
      . Systematic Review and External Validation of Prediction Models Based on Symptoms and Biomarkers for Identifying Endoscopic Activity in Crohn’s Disease. Clin Gastroenterol Hepatol 2020;18:1704–18. doi:10.1016/j.cgh.2019.12.014
      OpenUrlCrossRefPubMed
    15. ↵
      1. Falvey JD,
      2. Hoskin T,
      3. Meijer B, et al
      . Disease activity assessment in IBD: clinical indices and biomarkers fail to predict endoscopic remission. Inflamm Bowel Dis 2015;21:824–31. doi:10.1097/MIB.0000000000000341
      OpenUrlCrossRefPubMed
    16. ↵
      1. de Jong MJ,
      2. Roosen D,
      3. Degens JHRJ, et al
      . Development and Validation of a Patient-reported Score to Screen for Mucosal Inflammation in Inflammatory Bowel Disease. J Crohns Colitis 2019;13:555–63. doi:10.1093/ecco-jcc/jjy196
      OpenUrlPubMed
    17. ↵
      1. Van Deen WK,
      2. van der Meulen-de Jong AE,
      3. Parekh NK, et al
      . Development and Validation of an Inflammatory Bowel Diseases Monitoring Index for Use With Mobile Health Technologies. Clin Gastroenterol Hepatol 2016;14:1742–50. doi:10.1016/j.cgh.2015.10.035
      OpenUrlPubMed
    18. ↵
      1. Bennebroek Evertsz’ F,
      2. Hoeks CCMQ,
      3. Nieuwkerk PT, et al
      . Development of the patient Harvey Bradshaw index and a comparison with a clinician-based Harvey Bradshaw index assessment of Crohn’s disease activity. J Clin Gastroenterol 2013;47:850–6. doi:10.1097/MCG.0b013e31828b2196
      OpenUrlCrossRefPubMed
    19. ↵
      1. Bennebroek Evertsz’ F,
      2. Nieuwkerk PT,
      3. Stokkers PCF, et al
      . The patient simple clinical colitis activity index (P-SCCAI) can detect ulcerative colitis (UC) disease activity in remission: a comparison of the P-SCCAI with clinician-based SCCAI and biological markers. J Crohns Colitis 2013;7:890–900. doi:10.1016/j.crohns.2012.11.007
      OpenUrlCrossRefPubMedWeb of Science
    20. ↵
      1. van Andel EM,
      2. Koopmann BDM,
      3. Crouwel F, et al
      . Systematic Review of Development and Content Validity of Patient-reported Outcome Measures in Inflammatory Bowel Disease: Do We Measure What We Measure? J Crohns Colitis 2020;14:1299–315. doi:10.1093/ecco-jcc/jjaa057
      OpenUrlPubMed
    21. ↵
      1. van Erp LW,
      2. van Gerven J,
      3. Bloem S, et al
      . Acceptance and Perceived Control are Independently Associated With Quality of Life in Inflammatory Bowel Disease: Introduction of a New Segmentation Model. J Crohn's Colitis 2021;15:1837–45. doi:10.1093/ecco-jcc/jjab082
      OpenUrlCrossRefPubMed
    22. ↵
      1. Bodger K,
      2. Ormerod C,
      3. Shackcloth D, et al
      . Development and validation of a rapid, generic measure of disease control from the patient’s perspective: the IBD-control questionnaire. Gut 2014;63:1092–102. doi:10.1136/gutjnl-2013-305600
      OpenUrlAbstract/FREE Full Text
    23. ↵
      1. Clara I,
      2. Lix LM,
      3. Walker JR, et al
      . The Manitoba IBD Index: evidence for a new and simple indicator of IBD activity. Am J Gastroenterol 2009;104:1754–63. doi:10.1038/ajg.2009.197
      OpenUrlCrossRefPubMed
    24. ↵
      1. Colombel J-F,
      2. Panaccione R,
      3. Bossuyt P, et al
      . Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet 2017;390:2779–89. doi:10.1016/S0140-6736(17)32641-7
      OpenUrlCrossRefPubMed
    25. ↵
      1. Lang-Schwarz C,
      2. Angeloni M,
      3. Agaimy A, et al
      . Validation of the “Inflammatory Bowel Disease-Distribution, Chronicity, Activity [IBD-DCA] Score” for Ulcerative Colitis and Crohns Disease. J Crohns Colitis 2021;15:1621–30. doi:10.1093/ecco-jcc/jjab055
      OpenUrlPubMed
    26. ↵
      1. Vespa E,
      2. D’Amico F,
      3. Sollai M, et al
      . Histological Scores in Patients with Inflammatory Bowel Diseases: The State of the Art. J Clin Med 2022;11. doi:10.3390/jcm11040939
    27. ↵
      1. Geboes K,
      2. Riddell R,
      3. Ost A, et al
      . A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut 2000;47:404–9. doi:10.1136/gut.47.3.404
      OpenUrlAbstract/FREE Full Text
    28. ↵
      1. Vickers AJ,
      2. van Calster B,
      3. Steyerberg EW
      . A simple, step-by-step guide to interpreting decision curve analysis. Diagn Progn Res 2019;3. doi:10.1186/s41512-019-0064-7
    29. ↵
      1. Fairbrass KM,
      2. Costantino SJ,
      3. Gracie DJ, et al
      . Prevalence of irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease in remission: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020;5:1053–62. doi:10.1016/S2468-1253(20)30300-9
      OpenUrlCrossRefPubMed
    30. ↵
      1. Haisma S-M,
      2. Galaurchi A,
      3. Almahwzi S, et al
      . Head-to-head comparison of three stool calprotectin tests for home use. PLoS One 2019;14:e0214751. doi:10.1371/journal.pone.0214751

    Supplementary materials

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    Footnotes

    • Contributors MP had the original idea for the study. LJ drafted the initial protocol. MP, LJ, ZM, TEHR, RLW, RCAvL and LB contributed to the protocol development and study design. RCAvL, LJ and LB planned the statistical analyses. LJ, MP, RCAvL, ZM, MR-C, LPLG, TEHR and RLW were involved in the initiation of the study at the local study sites and are involved in the conduct of the trial and acquisition of data. LJ led the writing of this manuscript. All authors contributed equally with comments and feedback to the conception and design of the study and the writing of this manuscript. All authors read and approved the final manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.