Incorporating Fecal Calprotectin into Clinical Practice for Patients with Moderate-to-Severely Active Ulcerative Colitis Treated with Biologics or Small-Molecule Inhibitors

Parambir S. Dulai*, Robert Battat, Maria Barsky, Nghia H. Nguyen, Christopher Ma, Neeraj Narula, Mahmoud Mosli, Niels Vande Casteele, Brigid S. Boland, Larry Prokop, M. Hassan Murad, Geert D'Haens, Brian G. Feagan, William J. Sandborn, Vipul Jairath, Siddharth Singh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

INTRODUCTION:We applied the Grading of Recommendations, Assessment, Development, and Evaluation framework to evaluate the performance of fecal calprotectin (FC) as an alternative to endoscopy in patients with moderate-to-severe ulcerative colitis (UC) treated with a biologic agent or tofacitinib.METHODS:Individual participant data from the trials of infliximab, golimumab, vedolizumab, and tofacitinib for UC were pooled to generate prevalence of endoscopic activity (Mayo endoscopy score) across different combinations of the rectal bleeding score (RBS) and stool frequency score (SFS). These estimates were then combined with the data from an updated systematic review of the operating properties of FC to generate clinical scenario-specific assessments of the performance of FC as a predictor of endoscopic disease activity. A prespecified threshold of acceptability for false-negative (FN) and false-positive (FP) test results was set at 5%.RESULTS:For patients with UC achieving RBS 0 + SFS 0/1, FC ≤ 50 g/g may avoid endoscopy in 50% patients with a FN rate <5%. Similarly, for patients with RBS 2/3 + SFS 2/3, FC ≥ 250 g/g potentially avoids endoscopy in approximately 50% patients with an FP rate <5%. The greatest uncertainty in the diagnostic performance for FC was observed in patients with UC achieving RBS 0 but having SFS 2/3, where FN and FP rates were consistently >10%, and endoscopic evaluation may be warranted.DISCUSSION:Two clinical scenarios were identified where FC can be used with confidence for monitoring treatment response to biologics or tofacitinib in patients with UC without the requirement for endoscopy.

Original languageEnglish (US)
Pages (from-to)885-894
Number of pages10
JournalAmerican Journal of Gastroenterology
Volume115
Issue number6
DOIs
StatePublished - Jun 1 2020

Funding

Guarantor of the article: Parambir S. Dulai, MD and Siddharth Singh, MD, MS. Specific author contributions: P.S.D. and S.S. created the study concept and design. P.S.D., R.B., M.B., N.H.N., M.M., N.V.C., L.P., and S.S. acquired the data. P.S.D., M.H.M., and S.S. conducted the analyses. P.S.D. and S.S. drafted the manuscript. All authors participated in the critical revision of the manuscript for important intellectual content. P.S.D. and S.S. provided study supervision. Financial support: P.S.D. is supported by an American Gastroenterology Association Research Scholar Award. S.S. is supported by an American College of Gastroenterology Junior Faculty Development Award #144271, Crohn’s and Colitis Foundation Career Development Award #404614, AGA-Pfizer Young Investigator Pilot Research Award in Inflammatory Bowel Disease, and the National Institute of Diabetes and Digestive and Kidney Diseases K23DK117058. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Potential competing interests: P.S.D. has received research support from Takeda, Pfizer, Abbvie, Janssen, Polymedco, ALPCO, Buhlmann, and consulting fees from Takeda, Pfizer, Abbvie and Janssen. C.M. has served as a consultant for Robarts Clinical Trials, advisory board for Janssen, AbbVie, speakers fees from Janssen, Pfizer. N.N. holds a McMaster University Department of Medicine Internal Career Award and has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, and Ferring. M.M. has received speaker and consultant fees for Takeda, Abbvie, Janssen, and Pfizer. N.V.C. has received research support from R-Biopharm and Takeda and consulting fees from Boehringer Ingelheim, Janssen, Pfizer, Progenity, Prometheus and Takeda, outside of the submitted work. B.S.B. has received research support from Takeda and Janssen, and consulting fees from Abbvie and Prometheus laboratories. G.D.H. has served as advisor for Abbvie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Bristol Meiers Squibb, Boerhinger Ingelheim, Celgene, Celltrion, Cosmo, Covidien, Ferring, DrFALK Pharma, Engene, Galapagos, Gilead, Glaxo Smith Kline, Hospira, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Novonordisk, Pfizer, Prometheus laboratories/Nestle, Protagonist, Receptos, Robarts Clinical Trials, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor and received speaker fees from Abbvie, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Shire, Millenium/ Takeda, Tillotts and Vifor. B.G.F. has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma, AbbVie, Novartis Pharmaceuticals, Centocor, Elan/ Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, Acto-Genix and Wyeth Pharmaceuticals; consulting fees from Millennium Pharmaceuticals, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, AstraZeneca, Serono, Genentech, Tillotts Pharma, Unity Pharmaceuticals, Albireo Pharma, Given Imaging, Salix Pharmaceuticals, Novonordisk, GSK, ActoGenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma and Sigmoid Pharma; and speaker’s bureau fees from UCB, AbbVie and J&J/Janssen. W.J.S. has received research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos; consulting fees from Abbvie,Allergan,Amgen,Arena Pharmaceuticals,Avexegen Therapeutics, BeiGene, Boehringer Ingelheim, Celgene, Celltrion, Conatus, Cosmo, Escalier Biosciences, Ferring, Forbion, Gen-entech, Gilead Sciences, Gossamer Bio, Incyte, Janssen, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lilly, Oppi-lan Pharma, Otsuka, Prizer, Precision IBD, Progenity, Prometheus Laboratories, Reistone, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust, HART), Series Therapeutics, Shire, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, Tigenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals; and stock or stock options from Bei-Gene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Precision IBD, Progenity, Ritter Pharmaceuticals, Ventyx Biosciences, Vimalan Biosciences. Spouse: Opthotech—consultant, stock options; Progenity—consultant, stock; Oppilan Pharma— employee, stock options; Escalier Biosciences—employee, stock options; Precision IBD—employee, stock options; Ventyx Biosciences—employee, stock options; Vimalan Biosciences— employee, stock options. V.J. has received has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Jans-sen, Robarts Clinical Trials, Topivert, Celltrion; speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, Pfizer. S.S. has received research grants from AbbVie and Janssen, and consulting fees from Takeda, Pfizer. All other authors declare no potential conflicts of interest.

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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