Original ArticleEndoscopyModeling Endoscopic Improvement after Induction Treatment With Mesalamine in Patients With Mild-to-Moderate Ulcerative Colitis
Section snippets
Data and Participants
We used data from an active-comparator, multicenter, randomized, non-inferiority trial of mesalamine (Clinicaltrials.gov NCT01903252). The study design and trial outcomes have been previously reported.10 Adults with mild-to-moderate UC, defined by a total Mayo Clinic Score11 (MCS) ≥5, rectal bleeding subscore ≥1, and Mayo endoscopic subscore (MES) ≥2 at baseline were randomized to receive 3.2 g oral mesalamine, administered as either two 1600 mg tablets once daily or four 400 mg tablets twice
Patients
A total of 726 patients were included, and 436 patients (60.1%) achieved endoscopic improvement at week 8. Mean disease duration was 5.3 years (standard deviation ±6.5 years), and mean baseline fecal calprotectin was 1108 μg/g (±1546 μg/g). Mean rectal bleeding subscore was 1.5 (±0.5), and mean baseline Geboes score was 4.3 (±1.3).
Modeling Endoscopic Improvement
Univariable associations with endoscopic improvement are summarized in Supplementary Table 1. Multivariable logistic regression analyses are presented in Table 1.
Discussion
Although targeting endoscopic endpoints is associated with improved long-term outcomes in patients with UC, repeated lower endoscopy to evaluate disease activity is time-intensive, costly, and invasive for patients. Furthermore, many practices are facing restricted endoscopy availability because of coronavirus disease 2019, leading to a situation where many patients with mild-to-moderate UC will not undergo repeat endoscopy to measure treatment response to mesalamine. Although existing
CRediT Authorship Contributions
Christopher Ma, MD, MPH (Conceptualization: Lead; Data curation: Supporting; Methodology: Lead; Supervision: Equal; Writing – original draft: Lead; Writing – review & editing: Lead)
Jenny Jeyarajah (Conceptualization: Supporting; Formal analysis: Lead; Writing – review & editing: Supporting)
Leonardo Guizzetti (Formal analysis: Lead; Writing – review & editing: Supporting)
Claire E. Parker (Writing – original draft: Supporting; Writing – review & editing: Supporting)
Siddharth Singh (Writing –
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Conflicts of interest The authors disclose the following: Christopher Ma has received consulting fees from AbbVie, AVIR Pharma Inc, Janssen, Pfizer, Robarts Clinical Trials, and Takeda; and speaker’s fees from AbbVie, Janssen, Pfizer, and Takeda. Jenny Jeyarajah is an employee of Robarts Clinical Trials, Inc. Leonardo Guizzetti is an employee of Robarts Clinical Trials, Inc. Claire Parker is an employee of Robarts Clinical Trials, Inc. Siddharth Singh has received research grants from AbbVie and consulting fees from AbbVie, Takeda, Pfizer, and AMAG Pharmaceuticals. Parambir Dulai is supported by an American Gastroenterology Association Research Scholar Award and has received research support and/or consulting fees from AbbVie, Takeda, Pfizer, Janssen, Buhlmann, Polymedco, and Prometheus. Geert D’Haens has received consulting fees from AbbVie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmo, Covidien/Medtronics, Dr. Falk Pharma, Engene, Ferring, Galapagos, Gilead, GlaxoSmithKline, Hospira, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millennium/Takeda, Mitsubishi Pharma, MSD, Mundipharma, Novo Nordisk, Pfizer Inc, Prometheus Laboratories/Nestle, Receptos, Robarts Clinical Trials, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, and Vifor; research grants from AbbVie, Falk, Ferring, MSD, Mundipharma, and Takeda; and lecture and/or speaker bureau fees from AbbVie, Ferring, Johnson and Johnson, Millennium/Takeda, MSD, Mundipharma, Norgine, Pfizer Inc, Shire, Tillotts, and Vifor. William Sandborn has received research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, AbbVie, Janssen, Takeda, Lilly, Celgene/Receptos, Pfizer, Prometheus Laboratories (now Prometheus Biosciences); consulting fees from AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Avexegen Therapeutics, BeiGene, Boehringer Ingelheim, Celgene, Celltrion, Conatus, Cosmo, Escalier Biosciences, Ferring, Forbion, Genentech, Gilead Sciences, Gossamer Bio, Incyte, Janssen, Kyowa Kirin Pharmaceutical Research, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pfizer, Progenity, Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories), Reistone, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust, HART), Seres 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 BeiGene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories), 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; Prometheus Biosciences (merger of Precision IBD and Prometheus Laboratories) - employee, stock options; Ventyx Biosciences – employee, stock options; Vimalan Biosciences – employee, stock options. Brian Feagan has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc, Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc, and Sigmoid Pharma; and speaker’s fees from UCB, AbbVie, and J&J/Janssen. Vipul Jairath has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion; and speaker’s fees from Takeda, Janssen, Shire, Ferring, AbbVie, and Pfizer.
Funding The randomized trial was funded in full by Tillotts Pharma, AG. Tillotts Pharma, AG had no role in the design, analysis, or writing of this manuscript. William Sandborn was supported in part by NIDDK-funded San Diego Digestive Diseases Research Center (P30 DK120515).