references.bib

@article{constantine-cooke2023,
	title = {Longitudinal {Fecal} {Calprotectin} {Profiles} {Characterize} {Disease} {Course} {Heterogeneity} in {Crohn}’s {Disease}},
	issn = {15423565},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1542356523002343},
	doi = {10.1016/j.cgh.2023.03.026},
	language = {en},
	urldate = {2023-05-17},
	journal = {Clinical Gastroenterology and Hepatology},
	author = {Constantine-Cooke, Nathan and Monterrubio-Gómez, Karla and Plevris, Nikolas and Derikx, Lauranne A.A.P. and Gros, Beatriz and Jones, Gareth-Rhys and Marioni, Riccardo E. and Lees, Charlie W. and Vallejos, Catalina A.},
	month = mar,
	year = {2023},
	pages = {S1542356523002343},
}

@article{Vind2006,
	doi = {10.1111/j.1572-0241.2006.00552.x},
	url = {https://doi.org/10.1111%2Fj.1572-0241.2006.00552.x},
	year = 2006,
	month = {jun},
	publisher = {Ovid Technologies (Wolters Kluwer Health)},
	volume = {101},
	number = {6},
	pages = {1274--1282},
	author = {Ida Vind and Lene Riis and Tine Jess and Elisabeth Knudsen and Natalia Pedersen and Margarita Elkj{\ae}r and Inger Bak Andersen and Vibeke Wewer and Peter N{\o}rregaard and Flemming Moesgaard and Flemming Bendtsen and Pia Munkholm},
	title = {Increasing Incidences of Inflammatory Bowel Disease and Decreasing Surgery Rates in Copenhagen City and County, 2003{\textendash}2005: A Population-Based Study from the Danish Crohn Colitis Database},
	journal = {The American Journal of Gastroenterology}
}

@article{Elhakeem2022,
	abstract = {Longitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. Our aim was to provide an accessible guide along with applied examples to using four sophisticated modelling procedures for describing nonlinear growth trajectories.},
	author = {Elhakeem, Ahmed and Hughes, Rachael A. and Tilling, Kate and Cousminer, Diana L. and Jackowski, Stefan A. and Cole, Tim J. and Kwong, Alex S. F. and Li, Zheyuan and Grant, Struan F. A. and Baxter-Jones, Adam D. G. and Zemel, Babette S. and Lawlor, Deborah A.},
	date = {2022/03/15},
	date-added = {2022-03-18 15:03:41 +0000},
	date-modified = {2022-03-18 15:03:41 +0000},
	doi = {10.1186/s12874-022-01542-8},
	id = {Elhakeem2022},
	isbn = {1471-2288},
	journal = {BMC Medical Research Methodology},
	number = {1},
	pages = {68},
	title = {Using linear and natural cubic splines, SITAR, and latent trajectory models to characterise nonlinear longitudinal growth trajectories in cohort studies},
	url = {https://doi.org/10.1186/s12874-022-01542-8},
	volume = {22},
	year = {2022},
	bdsk-url-1 = {https://doi.org/10.1186/s12874-022-01542-8}
}

@Article{Proust-Lima2017,
  title = {Estimation of Extended Mixed Models Using Latent Classes and Latent Processes: The {R} Package {lcmm}},
  author = {C\'ecile Proust-Lima and Viviane Philipps and Benoit Liquet},
  journal = {Journal of Statistical Software},
  year = {2017},
  volume = {78},
  number = {2},
  pages = {1--56},
  doi = {10.18637/jss.v078.i02},
}

@article{Jenkinson2020,
	doi = {10.1093/ecco-jcc/jjaa044},
	url = {https://doi.org/10.1093%2Fecco-jcc%2Fjjaa044},
	year = 2020,
	month = {aug},
	publisher = {Oxford University Press ({OUP})},
	volume = {14},
	number = {9},
	pages = {1241--1247},
	author = {P W Jenkinson and N Plevris and S Siakavellas and M Lyons and I D Arnott and D Wilson and A J M Watson and G-R Jones and C W Lees},
	title = {Temporal Trends in Surgical Resection Rates and Biologic Prescribing in Crohn's Disease: A Population-based Cohort Study},
	journal = {Journal of Crohn{\textquotesingle}s and Colitis}
}

@article{Jones2019,
	doi = {10.1136/gutjnl-2019-318936},
	url = {https://doi.org/10.1136%2Fgutjnl-2019-318936},
	year = 2019,
	month = {jul},
	publisher = {{BMJ}},
	volume = {68},
	number = {11},
	pages = {1953--1960},
	author = {Gareth-Rhys Jones and Mathew Lyons and Nikolas Plevris and Philip W Jenkinson and Cathy Bisset and Christopher Burgess and Shahida Din and James Fulforth and Paul Henderson and Gwo-Tzer Ho and Kathryn Kirkwood and Colin Noble and Alan G Shand and David C Wilson and Ian DR Arnott and Charlie W Lees},
	title = {{IBD} prevalence in Lothian, Scotland, derived by capture-recapture methodology},
	journal = {Gut}
}

@incollection{harrell2015,
  title = {General {{Aspects}} of {{Fitting Regression Models}}},
  booktitle = {Regression {{Modeling Strategies}}: {{With Applications}} to {{Linear Models}}, {{Logistic}} and {{Ordinal Regression}}, and {{Survival Analysis}}},
  author = {Harrell, Frank E.},
  editor = {Harrell, Frank E., {\relax Jr}.},
  year = {2015},
  series = {Springer {{Series}} in {{Statistics}}},
  pages = {13--44},
  publisher = {{Springer International Publishing}},
  address = {{Cham}},
  doi = {10.1007/978-3-319-19425-7_2},
  urldate = {2023-07-17},
  abstract = {The ordinary multiple linear regression model is frequently used and has parameters that are easily interpreted. In this chapter we study a general class of regression models, those stated in terms of a weighted sum of a set of independent or predictor variables. It is shown that after linearizing the model with respect to the predictor variables, the parameters in such regression models are also readily interpreted. Also, all the designs used in ordinary linear regression can be used in this general setting. These designs include analysis of variance (ANOVAANOVA) setups, interaction effects, and nonlinear effects. Besides describing and interpreting general regression models, this chapter also describes, in general terms, how the three types of assumptions of regression models can be examined.},
  isbn = {978-3-319-19425-7},
  langid = {english},
  keywords = {Distributional Assumption,Linear Regression Model,Recursive Partitioning,Spline Function,White Blood Count},
  file = {/Users/s1961592/Zotero/storage/LDLQ56YB/Harrell_2015_General Aspects of Fitting Regression Models.pdf}
}

@article{Noor2024,
title = {A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial},
journal = {The Lancet Gastroenterology & Hepatology},
volume = {9},
number = {5},
pages = {415-427},
year = {2024},
issn = {2468-1253},
doi = {https://doi.org/10.1016/S2468-1253(24)00034-7},
url = {https://www.sciencedirect.com/science/article/pii/S2468125324000347},
author = {Nurulamin M Noor and James C Lee and Simon Bond and Francis Dowling and Biljana Brezina and Kamal V Patel and Tariq Ahmad and Paul J Banim and James W Berrill and Rachel Cooney and Juan {De La Revilla Negro} and Shanika {de Silva} and Shahida Din and Dharmaraj Durai and John N Gordon and Peter M Irving and Matthew Johnson and Alexandra J Kent and Klaartje B Kok and Gordon W Moran and Craig Mowat and Pritash Patel and Chris S Probert and Tim Raine and Rebecca Saich and Abigail Seward and Dan Sharpstone and Melissa A Smith and Sreedhar Subramanian and Sara S Upponi and Alan Wiles and Horace R T Williams and Gijs R {van den Brink} and Séverine Vermeire and Vipul Jairath and Geert R D'Haens and Eoin F McKinney and Paul A Lyons and James O Lindsay and Nicholas A Kennedy and Kenneth G C Smith and Miles Parkes and Nurulamin Noor and James Lee and Simon Bond and Francis Dowling and Biljana Brezina and Kamal Patel and Tariq Ahmad and Paul Banim and James Berrill and Rachel Cooney and Juan {De La Revilla Negro} and Shanika {de Silva} and Shahida Din and Dharmaraj Durai and John Gordon and Peter Irving and Matthew Johnson and Alexandra Kent and Klaartje Bel Kok and Gordon Moran and Craig Mowat and Pritash Patel and Chris Probert and Tim Raine and Rebecca Saich and Abigail Seward and Dan Sharpstone and Melissa Smith and Sreedhar Subramanian and Sara Upponi and Alan Wiles and Horace Williams and Gijs {van Den Brink} and Severine Vermeire and Vipul Jairath and Geert D'Haens and Eoin McKinney and Paul Lyons and James Lindsay and Nicholas Kennedy and Kenneth Smith and Miles Parkes and Clare Allcock and Suhaylah Bhatti and Jonathan Blackwell and Robert Boulton-Jones and Matthew Brookes and Rhys Butcher and Jeffrey Butterworth and Karlena Champion and Rakesh Chaudhary and Andy Cole and Lauranne Derikx and Anjan Dhar and Mary Flowerdew and Rishi Goel and Ailsa Hart and Rory Hughes and Babur Javaid and Paul Knight and Jacinta Lee and Charlie Lees and Emma Levell and Andy Li and Charles Murray and Leisha O'Brien and Gareth Parkes and Richard Pollok and Sam Powles and Arvind Ramdas and Philip Smith and Richard Ally Speight and Simon Travis and Sean Weaver and Emma Wesley},
abstract = {Summary
Background
Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies.
Methods
PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP >upper limit of normal or faecal calprotectin ≥200 μg/g, or both), while remission was the converse—ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 μg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228).
Findings
Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0–191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker–treatment interaction effect (absolute difference 1 percentage points, 95% CI –15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p<0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight).
Interpretation
Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease.
Funding
Wellcome and PredictImmune Ltd.}
}

@article{Dhaens2008,
title = {Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: An open randomised trial},
journal = {The Lancet},
volume = {371},
number = {9613},
pages = {660-667},
year = {2008},
issn = {0140-6736},
doi = {https://doi.org/10.1016/S0140-6736(08)60304-9},
url = {https://www.sciencedirect.com/science/article/pii/S0140673608603049},
author = {Geert D'Haens and Filip Baert and Gert {van Assche} and Philip Caenepeel and Philippe Vergauwe and Hans Tuynman and Martine {De Vos} and Sander {van Deventer} and Larry Stitt and Allan Donner and Severine Vermeire and Frank J {Van De Mierop} and Jean-Charles R Coche and Janneke {van der Woude} and Thomas Ochsenkühn and Ad A {van Bodegraven} and Philippe P {Van Hootegem} and Guy L Lambrecht and Fazia Mana and Paul Rutgeerts and Brian G Feagan and Daniel Hommes},
abstract = {Summary
Background
Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab.
Methods
We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710.
Findings
Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60·0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35·9%) of 64 controls, for an absolute difference of 24·1% (95% CI 7·3–40·8, p=0·0062). Corresponding rates at week 52 were 40/65 (61·5%) and 27/64 (42·2%) (absolute difference 19·3%, 95% CI 2·4–36·3, p=0·0278). 20 of the 65 patients (30·8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25·3%) controls (p=1·0).
Interpretation
Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.}
}


 @article{Lewis2023,
   title = {Incidence, prevalence, and racial and ethnic distribution of inflammatory bowel disease in the United States},
   volume = {165},
   ISSN = {0016-5085},
   url = {http://dx.doi.org/10.1053/j.gastro.2023.07.003},
   DOI = {10.1053/j.gastro.2023.07.003},
   number = {5},
   journal = {Gastroenterology},
   publisher = {Elsevier BV},
   author = {Lewis, James D. and Parlett, Lauren E. and Jonsson Funk, Michele L. and Brensinger, Colleen and Pate, Virginia and Wu, Qufei and Dawwas, Ghadeer K. and Weiss, Alexandra and Constant, Brad D. and McCauley, Maureen and Haynes, Kevin and Yang, Jeff Yufeng and Schaubel, Douglas E. and Hurtado-Lorenzo, Andres and Kappelman, Michael David},
   year = {2023},
   month = nov,
   pages = {1197-1205.e2}
}