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Vedolizumab Dose Escalation Improves Therapeutic Response in a Subset of Patients with Ulcerative Colitis

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Abstract

Background

The Gemini trial failed to detect a significant difference in response rate for patients with ulcerative colitis (UC) randomized to standard (every 8 week) vedolizumab dosing vs escalated (every 4 week) dosing. Subsequent real-world data imply the Gemini trial design may have obscured a benefit of escalated dosing.

Aims

We investigated outcomes after vedolizumab dose escalation for patients with UC. We also explored potential clinical predictors of dose escalation requirement.

Methods

In this retrospective study, we included patients with UC who received vedolizumab between 1/2017-1/2019. We compared rates of clinical response (decrease in partial Mayo score by ≥ 2) and remission (partial Mayo < 2) for standard vs escalated dosing.

Results

Among the 90 patients reviewed, 52 achieved and maintained remission on standard dosing. The average time to remission with standard dosing was 33.3 ± 6.6 weeks. After an average of 56.3 ± 7.4 weeks standard dosing, 24 patients (22 “partial responders” and 2 “non-responders”) were dose-escalated. Of the 22 “partial responders” dose-escalated, 10 (45%) achieved remission, 10 (45%) achieved further improvement. Neither “non-responder” demonstrated further clinical benefit. Prior anti-tumor necrosis factor (anti-TNF) biologic exposure predicted dose escalation requirement (p = 0.008). Patients requiring dose escalation had more severe disease at baseline as measured by both full Mayo (p = 0.009) and partial Mayo scores (p = 0.01).

Conclusions

We show dose escalation benefited patients with UC who exhibit a “partial response” to standard dosing. Early vedolizumab dose escalation should be considered in both patients with severe disease and those with prior anti-TNF experience.

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Acknowledgments

The project described was supported by the NIH National Center for Advancing Translational Sciences through Grant Number UL1TR001998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We would also like to thank Nancy Mannon RPh, for her assistance with compiling patients meeting eligibility criteria for study analysis.

Funding

CP is supported by the National Institutes of Health, Grant TL1TR001997 of CCTS funding. The authors’ work is also supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R21DK118954. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported in part by Merit Review Award# I01CX001353 to TAB from the United States (U.S.) Department of Veterans Affairs Laboratory Research and Development Program.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, University of Kentucky College of Medicine, 800 Rose Street, MN649, Lexington, KY, 40536, USA

    Courtney Perry, Ahmed Elmoursi, Deborah Flomenhoft & Terrence A. Barrett

  2. Dr. Bing Zhang Department of Statistics, University of Kentucky College of Arts and Sciences, Lexington, KY, USA

    Leon Su & Arnold Stromberg

  3. Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY, USA

    Kyle Fischer, Cody Kern, Alden Currier, Praneeth Kudaravalli, Olalekan Akanbi, Nishant Tripathi & Pradeep Yarra

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  1. Courtney Perry
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  2. Kyle Fischer
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Correspondence to Courtney Perry.

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Conflict of interest

Dr. Barrett has consulted and received honoraria for speaker’s bureau activities for Takeda and AbbVie pharmaceutical companies.

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Perry, C., Fischer, K., Elmoursi, A. et al. Vedolizumab Dose Escalation Improves Therapeutic Response in a Subset of Patients with Ulcerative Colitis. Dig Dis Sci 66, 2051–2058 (2021). https://doi.org/10.1007/s10620-020-06486-x

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