Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease

Syedreza A. Haider; Abhijeet Yadav; Courtney Perry; Leon Su; Olalekan Akanbi; Praneeth Kudaravalli; Nishant Tripathi; Mahmoud A. Hashim; Mohammed Abdelsalam; Mohamed Hussein; Ahmed Elkheshen; Vihang Patel; Saad Emhmed Ali; Latoya Lamb; Karen Ingram; Casie Mayne; Amy B. Stuffelbeam; Deborah Flomenhoft; Arnold Stromberg; Terrence A. Barrett

doi:10.1177/1756284820959245

Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease

Syedreza A. Haider, Abhijeet Yadav, Courtney Perry, Leon Su, Olalekan Akanbi, Praneeth Kudaravalli, Nishant Tripathi, Mahmoud A. Hashim, Mohammed Abdelsalam, Mohamed Hussein, Ahmed Elkheshen, Vihang Patel, Saad Emhmed Ali, Latoya Lamb, Karen Ingram, Casie Mayne, Amy B. Stuffelbeam, Deborah Flomenhoft, Arnold Stromberg, Terrence A. Barrett

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn’s disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as “failing” standard dosing at 42 weeks who were not dose escalated. Results: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 (p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL (p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. Conclusion: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

Original language	English
Journal	Therapeutic Advances in Gastroenterology
Volume	13
DOIs	https://doi.org/10.1177/1756284820959245
State	Published - 2020

Bibliographical note

Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. 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.

Funding Information:
We thank Nancy Mannon, PharmD (College of Pharmacy) for assistance in patient identification and Brandi Waskul (Division of Digestive Disease and Nutrition, University of Kentucky College of Medicine) for administrative assistance. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. 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.

Publisher Copyright:
© The Author(s), 2020.

Keywords

Crohn’s disease
dose escalation
remission
ustekinumab

ASJC Scopus subject areas

Gastroenterology

Access to Document

10.1177/1756284820959245

Cite this

Haider, S. A., Yadav, A., Perry, C., Su, L., Akanbi, O., Kudaravalli, P., Tripathi, N., Hashim, M. A., Abdelsalam, M., Hussein, M., Elkheshen, A., Patel, V., Ali, S. E., Lamb, L., Ingram, K., Mayne, C., Stuffelbeam, A. B., Flomenhoft, D., Stromberg, A., & Barrett, T. A. (2020). Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease. Therapeutic Advances in Gastroenterology, 13. https://doi.org/10.1177/1756284820959245

@article{e4e2d66dea4f48e48fcd6290b4500e11,

title = "Ustekinumab dose escalation improves clinical responses in refractory Crohn{\textquoteright}s disease",

abstract = "Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn{\textquoteright}s disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as “failing” standard dosing at 42 weeks who were not dose escalated. Results: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 (p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL (p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. Conclusion: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.",

keywords = "Crohn{\textquoteright}s disease, dose escalation, remission, ustekinumab",

author = "Haider, {Syedreza A.} and Abhijeet Yadav and Courtney Perry and Leon Su and Olalekan Akanbi and Praneeth Kudaravalli and Nishant Tripathi and Hashim, {Mahmoud A.} and Mohammed Abdelsalam and Mohamed Hussein and Ahmed Elkheshen and Vihang Patel and Ali, {Saad Emhmed} and Latoya Lamb and Karen Ingram and Casie Mayne and Stuffelbeam, {Amy B.} and Deborah Flomenhoft and Arnold Stromberg and Barrett, {Terrence A.}",

note = "Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. CP is supported by the National Institutes of Health, Grant TL1TR001997 of CCTS funding. The authors{\textquoteright} 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. Funding Information: We thank Nancy Mannon, PharmD (College of Pharmacy) for assistance in patient identification and Brandi Waskul (Division of Digestive Disease and Nutrition, University of Kentucky College of Medicine) for administrative assistance. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. 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. Publisher Copyright: {\textcopyright} The Author(s), 2020.",

year = "2020",

doi = "10.1177/1756284820959245",

language = "English",

volume = "13",

}

Haider, SA, Yadav, A, Perry, C, Su, L, Akanbi, O, Kudaravalli, P, Tripathi, N, Hashim, MA, Abdelsalam, M, Hussein, M, Elkheshen, A, Patel, V, Ali, SE, Lamb, L, Ingram, K, Mayne, C, Stuffelbeam, AB, Flomenhoft, D, Stromberg, A & Barrett, TA 2020, 'Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease', Therapeutic Advances in Gastroenterology, vol. 13. https://doi.org/10.1177/1756284820959245

TY - JOUR

T1 - Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease

AU - Haider, Syedreza A.

AU - Yadav, Abhijeet

AU - Perry, Courtney

AU - Su, Leon

AU - Akanbi, Olalekan

AU - Kudaravalli, Praneeth

AU - Tripathi, Nishant

AU - Hashim, Mahmoud A.

AU - Abdelsalam, Mohammed

AU - Hussein, Mohamed

AU - Elkheshen, Ahmed

AU - Patel, Vihang

AU - Ali, Saad Emhmed

AU - Lamb, Latoya

AU - Ingram, Karen

AU - Mayne, Casie

AU - Stuffelbeam, Amy B.

AU - Flomenhoft, Deborah

AU - Stromberg, Arnold

AU - Barrett, Terrence A.

N1 - Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. 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. Funding Information: We thank Nancy Mannon, PharmD (College of Pharmacy) for assistance in patient identification and Brandi Waskul (Division of Digestive Disease and Nutrition, University of Kentucky College of Medicine) for administrative assistance. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. 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. Publisher Copyright: © The Author(s), 2020.

PY - 2020

Y1 - 2020

N2 - Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn’s disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as “failing” standard dosing at 42 weeks who were not dose escalated. Results: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 (p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL (p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. Conclusion: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

AB - Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn’s disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as “failing” standard dosing at 42 weeks who were not dose escalated. Results: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 (p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL (p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. Conclusion: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

KW - Crohn’s disease

KW - dose escalation

KW - remission

KW - ustekinumab

UR - http://www.scopus.com/inward/record.url?scp=85092553379&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85092553379&partnerID=8YFLogxK

U2 - 10.1177/1756284820959245

DO - 10.1177/1756284820959245

M3 - Article

AN - SCOPUS:85092553379

VL - 13

ER -

Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this