Efficacy and Safety of Advanced Therapies for Moderately to Severely Active Ulcerative Colitis at Induction and Maintenance: An Indirect Treatment Comparison Using Bayesian Network Meta-analysis – ScienceOpen
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      Efficacy and Safety of Advanced Therapies for Moderately to Severely Active Ulcerative Colitis at Induction and Maintenance: An Indirect Treatment Comparison Using Bayesian Network Meta-analysis

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      , MD, FRCPC , , MPH, , MD, , MD, PhD, , MD, PhD, , MD, PhD, MSc (CRDSA), AGAF, , PhD, , MD, PhD, , MBBS, MRCS, MSC, MBA, , PhD, , MS, MSc, PhD, , MS
      Crohn's & Colitis 360
      Oxford University Press
      ulcerative colitis, clinical trials, advanced therapies, network meta-analysis

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          Abstract

          Background

          Given rapid innovation in advanced therapies for moderately to severely active ulcerative colitis (UC), we investigated their comparative efficacy and safety during induction and maintenance through network meta-analysis.

          Methods

          Using Bayesian methods, endpoints of clinical remission and clinical response per Full Mayo score, and endoscopic improvement were assessed in bio-naive and -exposed populations. Safety was assessed in overall populations by all adverse events (AEs), serious AEs, discontinuation due to AEs, and serious infections. Phase 3 randomized controlled trials were identified via systematic literature review, including the following advanced therapies: infliximab, adalimumab, vedolizumab, golimumab, tofacitinib, ustekinumab, filgotinib, ozanimod, and upadacitinib. Random effects models were used to address between-study heterogeneity. Intent-to-treat (ITT) efficacy rates were calculated by adjusting maintenance outcomes by likelihood of induction response.

          Results

          Out of 48 trials identified, 23 were included. Across all outcomes and regardless of prior biologic exposure, ITT efficacy rates were highest for upadacitinib, owing to its highest ranking for all efficacy outcomes in induction and for all but clinical remission during maintenance among bio-naive induction responders. For all advanced therapies versus placebo, there were no significant differences in serious AEs or serious infections across therapies. For all AEs, golimumab had higher odds versus placebo during maintenance; for discontinuation due to AEs, upadacitinib had lower odds versus placebo during induction, while ustekinumab and vedolizumab had lower odds versus placebo during maintenance.

          Conclusions

          Upadacitinib may be the most efficacious therapy for moderately to severely active UC based on ITT analyses, with similar safety across advanced therapies.

          Graphical Abstract

          Graphical Abstract

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          Most cited references25

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          The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

          Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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            Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.

            To present some simple graphical and quantitative ways to assist interpretation and improve presentation of results from multiple-treatment meta-analysis (MTM). We reanalyze a published network of trials comparing various antiplatelet interventions regarding the incidence of serious vascular events using Bayesian approaches for random effects MTM, and we explore the advantages and drawbacks of various traditional and new forms of quantitative displays and graphical presentations of results. We present the results under various forms, conventionally based on the mean of the distribution of the effect sizes; based on predictions; based on ranking probabilities; and finally, based on probabilities to be within an acceptable range from a reference. We show how to obtain and present results on ranking of all treatments and how to appraise the overall ranks. Bayesian methodology offers a multitude of ways to present results from MTM models, as it enables a natural and easy estimation of all measures based on probabilities, ranks, or predictions. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.

              We assessed oral 5-aminosalicylic acid (5-ASA) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind, placebo-controlled trial. Patients were randomly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks. The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians' assessments at three-week intervals and by patients' recordings of daily symptoms. Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo (P less than 0.0001, rank-sum test). At a dosage of 1.6 g per day, the response was twice as good as with placebo, but the difference did not reach statistical significance (P = 0.51). Age, sex, duration of disease, duration of active symptoms, or extent of disease did not affect the clinical outcome. We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy, at least in the short term, for mildly to moderately active ulcerative colitis.
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                Author and article information

                Contributors
                Journal
                Crohns Colitis 360
                Crohns Colitis 360
                crohnscolitis360
                Crohn's & Colitis 360
                Oxford University Press (US )
                2631-827X
                April 2023
                01 March 2023
                01 March 2023
                : 5
                : 2
                : otad009
                Affiliations
                Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary , Calgary, Alberta, Canada
                Medicus Economics LLC , Milton, Massachusetts, USA
                Cedars-Sinai Medical Center , Los Angeles, California, USA
                Department of Gastroenterology & Hepatology, University Hospital Leuven , KU Leuven, Leuven, Belgium
                Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Department of Gastroenterology, University Vita-Salute San Raffaele , Milan, Italy
                Department of Medicine, Division of Gastroenterology, University of Michigan , Ann Arbor, Michigan, USA
                Cytel, Inc. , Waltham, Massachusetts, USA
                AbbVie Inc. , North Chicago, Illinois, USA
                AbbVie Inc. , North Chicago, Illinois, USA
                AbbVie Inc. , North Chicago, Illinois, USA
                AbbVie Inc. , North Chicago, Illinois, USA
                Medicus Economics LLC , Milton, Massachusetts, USA
                Author notes
                Address correspondence to: Remo Panaccione, MD, FRCPC, Rm 6D32, TRW Building, 3280 Hospitals Drive NW, Calgary, AB T3R1B1, Canada ( rpanacci@ 123456ucalgary.ca ).
                Author information
                https://orcid.org/0000-0002-5247-940X
                https://orcid.org/0000-0002-9329-847X
                https://orcid.org/0000-0002-2591-5165
                https://orcid.org/0000-0001-9942-3019
                https://orcid.org/0000-0001-7341-1351
                https://orcid.org/0000-0001-7261-1933
                https://orcid.org/0000-0003-1537-7110
                Article
                otad009
                10.1093/crocol/otad009
                10045885
                36998249
                951f73f2-ae7d-4996-aa63-0974dcb96bf0
                © The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 September 2022
                : 25 January 2023
                : 28 March 2023
                Page count
                Pages: 17
                Funding
                Funded by: AbbVie Inc., DOI 10.13039/100006483;
                Categories
                Observations and Research
                AcademicSubjects/MED00260
                AcademicSubjects/MED00760
                AcademicSubjects/MED00972

                ulcerative colitis,clinical trials,advanced therapies,network meta-analysis

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