Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study

Laura E. Targownik; Eric I. Benchimol; Charles N. Bernstein; Harminder Singh; Lisa Lix; A. Tennakoon; Stella Leung; Antonio Aviña; Stephanie Coward; Jennifer Jones; Gil Kaplan; Sanjay K. Murthy; Geoffrey C. Nguyen; Juan Nicolás Peña-Sánchez

doi:10.1016/j.cgh.2018.11.003

Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study

Laura E. Targownik, Eric I. Benchimol, Charles N. Bernstein, Harminder Singh, Lisa Lix, A. Tennakoon, Stella Leung, Antonio Aviña, Stephanie Coward, Jennifer Jones, Gil Kaplan, Sanjay K. Murthy, Geoffrey C. Nguyen, Juan Nicolás Peña-Sánchez

Medicine

Medicine

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29 Citations (Scopus)

Abstract

Background & Aims: Although guidelines recommend inclusion of immune modulators in anti-tumor necrosis factor (TNF) initiation therapy for Crohn's disease (CD) or ulcerative colitis (UC), there are limited data on the incremental effectiveness of this treatment strategy from the real world. Methods: We collected data from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database on persons with CD (n=852) or UC (n=303), from 2001 through 2016, who began treatment with a TNF antagonist. New and/or continuing users of immunomodulators at the time anti-TNF therapy began were considered recipients of combination therapy. The main outcome was treatment ineffectiveness (IBD-related hospitalization, intestinal resection, corticosteroid use, or change of anti-TNF agent) during TNF antagonist-based therapy or within 90 days after the anti-TNF agent was discontinued. We used Cox proportional hazards models to assess the association between concomitant use of immunomodulators and treatment ineffectiveness. Results: In patients with CD, combination therapy was associated with a significant decrease in likelihood of treatment ineffectiveness (adjusted hazard ratio [aHR] for ineffectiveness, 0.62; 95% CI, 0.49–0.79). However, this association was not significant in patients with UC (aHR, 0.82; 95% CI, 0.56–1.20). In patients with CD, combination therapy was also associated with increased time to first IBD-related hospitalization (aHR 0.53; 95% CI, 0.36–0.80) and switching anti-TNF agents (aHR, 0.63; 95% CI, 0.41–0.97), but not associated with IBD-related surgery (aHR, 0.76; 95% CI, 0.51–1.12) or new or recurrent use of corticosteroids (aHR, 0.75; 95% CI, 0.55–1.04). Conclusion: In an analysis of a database of real-world patients with IBD, we associated initiation therapy with a combination immune modulators and anti-TNF agents with a decreased likelihood of treatment ineffectiveness for patients with CD but not UC.

Original language	English
Pages (from-to)	1788-1798.e2
Journal	Clinical Gastroenterology and Hepatology
Volume	17
Issue number	9
DOIs	https://doi.org/10.1016/j.cgh.2018.11.003
Publication status	Published - Aug 2019

Bibliographical note

Funding Information:
Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation. Conflicts of interest These authors disclose the following: Laura Targownik has received investigator initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, and Mallinckrodt USA. Charles Bernstein has served on advisory Boards for AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, and Pfizer Canada; has been a Consultant for Mylan Pharmaceuticals; has received educational grants from AbbVie Canada, Shire Canada, Takeda Canada, and Janssen Canada; has been on Speaker's panel for AbbVie Canada, Ferring Canada, and Shire Canada; and has received research funding from AbbVie Canada. Harminder Singh has been on advisory board of Pendopharm, Ferring, and Merck Canada and has received research funding from Merck Canada. Jennifer Jones has been on advisory boards, acted as a consultant, and has been a speaker for Advisory, and received consultant, speaker fees for Janssen and AbbVie. Gil Kaplan has received speaking or consultancy honoraria from AbbVie, Janssen, Pfizer, and Shire and has received a grant from AbbVie, Janssen, Merck, and Shire. Sanjay Murthy has served on advisory boards for AbbVie, Ferring, Shire, Takeda, and Pfizer. The remaining authors disclose no conflicts. Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation. The authors thank the Canadian Gastrointestinal Epidemiologic Consortium for their technical support. Conflicts of interest These authors disclose the following: Laura Targownik has received investigator initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, and Mallinckrodt USA. Charles Bernstein has served on advisory Boards for AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, and Pfizer Canada; has been a Consultant for Mylan Pharmaceuticals; has received educational grants from AbbVie Canada, Shire Canada, Takeda Canada, and Janssen Canada; has been on Speaker's panel for AbbVie Canada, Ferring Canada, and Shire Canada; and has received research funding from AbbVie Canada. Harminder Singh has been on advisory board of Pendopharm, Ferring, and Merck Canada and has received research funding from Merck Canada. Jennifer Jones has been on advisory boards, acted as a consultant, and has been a speaker for Advisory, and received consultant, speaker fees for Janssen and AbbVie. Gil Kaplan has received speaking or consultancy honoraria from AbbVie, Janssen, Pfizer, and Shire and has received a grant from AbbVie, Janssen, Merck, and Shire. Sanjay Murthy has served on advisory boards for AbbVie, Ferring, Shire, Takeda, and Pfizer. The remaining authors disclose no conflicts. Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation.

Publisher Copyright:
© 2019 AGA Institute

ASJC Scopus Subject Areas

Hepatology
Gastroenterology

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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Targownik, L. E., Benchimol, E. I., Bernstein, C. N., Singh, H., Lix, L., Tennakoon, A., Leung, S., Aviña, A., Coward, S., Jones, J., Kaplan, G., Murthy, S. K., Nguyen, G. C., & Peña-Sánchez, J. N. (2019). Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study. Clinical Gastroenterology and Hepatology, 17(9), 1788-1798.e2. https://doi.org/10.1016/j.cgh.2018.11.003

Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study. / Targownik, Laura E.; Benchimol, Eric I.; Bernstein, Charles N. et al.
In: Clinical Gastroenterology and Hepatology, Vol. 17, No. 9, 08.2019, p. 1788-1798.e2.

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

Targownik, LE, Benchimol, EI, Bernstein, CN, Singh, H, Lix, L, Tennakoon, A, Leung, S, Aviña, A, Coward, S, Jones, J, Kaplan, G, Murthy, SK, Nguyen, GC & Peña-Sánchez, JN 2019, 'Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study', Clinical Gastroenterology and Hepatology, vol. 17, no. 9, pp. 1788-1798.e2. https://doi.org/10.1016/j.cgh.2018.11.003

Targownik LE, Benchimol EI, Bernstein CN, Singh H, Lix L, Tennakoon A et al. Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study. Clinical Gastroenterology and Hepatology. 2019 Aug;17(9):1788-1798.e2. doi: 10.1016/j.cgh.2018.11.003

Targownik, Laura E. ; Benchimol, Eric I. ; Bernstein, Charles N. et al. / Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study. In: Clinical Gastroenterology and Hepatology. 2019 ; Vol. 17, No. 9. pp. 1788-1798.e2.

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title = "Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study",

abstract = "Background & Aims: Although guidelines recommend inclusion of immune modulators in anti-tumor necrosis factor (TNF) initiation therapy for Crohn's disease (CD) or ulcerative colitis (UC), there are limited data on the incremental effectiveness of this treatment strategy from the real world. Methods: We collected data from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database on persons with CD (n=852) or UC (n=303), from 2001 through 2016, who began treatment with a TNF antagonist. New and/or continuing users of immunomodulators at the time anti-TNF therapy began were considered recipients of combination therapy. The main outcome was treatment ineffectiveness (IBD-related hospitalization, intestinal resection, corticosteroid use, or change of anti-TNF agent) during TNF antagonist-based therapy or within 90 days after the anti-TNF agent was discontinued. We used Cox proportional hazards models to assess the association between concomitant use of immunomodulators and treatment ineffectiveness. Results: In patients with CD, combination therapy was associated with a significant decrease in likelihood of treatment ineffectiveness (adjusted hazard ratio [aHR] for ineffectiveness, 0.62; 95% CI, 0.49–0.79). However, this association was not significant in patients with UC (aHR, 0.82; 95% CI, 0.56–1.20). In patients with CD, combination therapy was also associated with increased time to first IBD-related hospitalization (aHR 0.53; 95% CI, 0.36–0.80) and switching anti-TNF agents (aHR, 0.63; 95% CI, 0.41–0.97), but not associated with IBD-related surgery (aHR, 0.76; 95% CI, 0.51–1.12) or new or recurrent use of corticosteroids (aHR, 0.75; 95% CI, 0.55–1.04). Conclusion: In an analysis of a database of real-world patients with IBD, we associated initiation therapy with a combination immune modulators and anti-TNF agents with a decreased likelihood of treatment ineffectiveness for patients with CD but not UC.",

author = "Targownik, {Laura E.} and Benchimol, {Eric I.} and Bernstein, {Charles N.} and Harminder Singh and Lisa Lix and A. Tennakoon and Stella Leung and Antonio Avi{\~n}a and Stephanie Coward and Jennifer Jones and Gil Kaplan and Murthy, {Sanjay K.} and Nguyen, {Geoffrey C.} and Pe{\~n}a-S{\'a}nchez, {Juan Nicol{\'a}s}",

note = "Funding Information: Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation. Conflicts of interest These authors disclose the following: Laura Targownik has received investigator initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, and Mallinckrodt USA. Charles Bernstein has served on advisory Boards for AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, and Pfizer Canada; has been a Consultant for Mylan Pharmaceuticals; has received educational grants from AbbVie Canada, Shire Canada, Takeda Canada, and Janssen Canada; has been on Speaker's panel for AbbVie Canada, Ferring Canada, and Shire Canada; and has received research funding from AbbVie Canada. Harminder Singh has been on advisory board of Pendopharm, Ferring, and Merck Canada and has received research funding from Merck Canada. Jennifer Jones has been on advisory boards, acted as a consultant, and has been a speaker for Advisory, and received consultant, speaker fees for Janssen and AbbVie. Gil Kaplan has received speaking or consultancy honoraria from AbbVie, Janssen, Pfizer, and Shire and has received a grant from AbbVie, Janssen, Merck, and Shire. Sanjay Murthy has served on advisory boards for AbbVie, Ferring, Shire, Takeda, and Pfizer. The remaining authors disclose no conflicts. Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation. The authors thank the Canadian Gastrointestinal Epidemiologic Consortium for their technical support. Conflicts of interest These authors disclose the following: Laura Targownik has received investigator initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, and Mallinckrodt USA. Charles Bernstein has served on advisory Boards for AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, and Pfizer Canada; has been a Consultant for Mylan Pharmaceuticals; has received educational grants from AbbVie Canada, Shire Canada, Takeda Canada, and Janssen Canada; has been on Speaker's panel for AbbVie Canada, Ferring Canada, and Shire Canada; and has received research funding from AbbVie Canada. Harminder Singh has been on advisory board of Pendopharm, Ferring, and Merck Canada and has received research funding from Merck Canada. Jennifer Jones has been on advisory boards, acted as a consultant, and has been a speaker for Advisory, and received consultant, speaker fees for Janssen and AbbVie. Gil Kaplan has received speaking or consultancy honoraria from AbbVie, Janssen, Pfizer, and Shire and has received a grant from AbbVie, Janssen, Merck, and Shire. Sanjay Murthy has served on advisory boards for AbbVie, Ferring, Shire, Takeda, and Pfizer. The remaining authors disclose no conflicts. Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation. Publisher Copyright: {\textcopyright} 2019 AGA Institute",

year = "2019",

month = aug,

doi = "10.1016/j.cgh.2018.11.003",

language = "English",

volume = "17",

pages = "1788--1798.e2",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

publisher = "W.B. Saunders Ltd",

number = "9",

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TY - JOUR

T1 - Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study

AU - Targownik, Laura E.

AU - Benchimol, Eric I.

AU - Bernstein, Charles N.

AU - Singh, Harminder

AU - Lix, Lisa

AU - Tennakoon, A.

AU - Leung, Stella

AU - Aviña, Antonio

AU - Coward, Stephanie

AU - Jones, Jennifer

AU - Kaplan, Gil

AU - Murthy, Sanjay K.

AU - Nguyen, Geoffrey C.

AU - Peña-Sánchez, Juan Nicolás

N1 - Funding Information: Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation. Conflicts of interest These authors disclose the following: Laura Targownik has received investigator initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, and Mallinckrodt USA. Charles Bernstein has served on advisory Boards for AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, and Pfizer Canada; has been a Consultant for Mylan Pharmaceuticals; has received educational grants from AbbVie Canada, Shire Canada, Takeda Canada, and Janssen Canada; has been on Speaker's panel for AbbVie Canada, Ferring Canada, and Shire Canada; and has received research funding from AbbVie Canada. Harminder Singh has been on advisory board of Pendopharm, Ferring, and Merck Canada and has received research funding from Merck Canada. Jennifer Jones has been on advisory boards, acted as a consultant, and has been a speaker for Advisory, and received consultant, speaker fees for Janssen and AbbVie. Gil Kaplan has received speaking or consultancy honoraria from AbbVie, Janssen, Pfizer, and Shire and has received a grant from AbbVie, Janssen, Merck, and Shire. Sanjay Murthy has served on advisory boards for AbbVie, Ferring, Shire, Takeda, and Pfizer. The remaining authors disclose no conflicts. Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation. The authors thank the Canadian Gastrointestinal Epidemiologic Consortium for their technical support. Conflicts of interest These authors disclose the following: Laura Targownik has received investigator initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada, and Mallinckrodt USA. Charles Bernstein has served on advisory Boards for AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, and Pfizer Canada; has been a Consultant for Mylan Pharmaceuticals; has received educational grants from AbbVie Canada, Shire Canada, Takeda Canada, and Janssen Canada; has been on Speaker's panel for AbbVie Canada, Ferring Canada, and Shire Canada; and has received research funding from AbbVie Canada. Harminder Singh has been on advisory board of Pendopharm, Ferring, and Merck Canada and has received research funding from Merck Canada. Jennifer Jones has been on advisory boards, acted as a consultant, and has been a speaker for Advisory, and received consultant, speaker fees for Janssen and AbbVie. Gil Kaplan has received speaking or consultancy honoraria from AbbVie, Janssen, Pfizer, and Shire and has received a grant from AbbVie, Janssen, Merck, and Shire. Sanjay Murthy has served on advisory boards for AbbVie, Ferring, Shire, Takeda, and Pfizer. The remaining authors disclose no conflicts. Funding Supported through a grant from the Crohn's and Colitis Canada Grants in Aid of Research and the Helmsley Foundation. Publisher Copyright: © 2019 AGA Institute

PY - 2019/8

Y1 - 2019/8

N2 - Background & Aims: Although guidelines recommend inclusion of immune modulators in anti-tumor necrosis factor (TNF) initiation therapy for Crohn's disease (CD) or ulcerative colitis (UC), there are limited data on the incremental effectiveness of this treatment strategy from the real world. Methods: We collected data from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database on persons with CD (n=852) or UC (n=303), from 2001 through 2016, who began treatment with a TNF antagonist. New and/or continuing users of immunomodulators at the time anti-TNF therapy began were considered recipients of combination therapy. The main outcome was treatment ineffectiveness (IBD-related hospitalization, intestinal resection, corticosteroid use, or change of anti-TNF agent) during TNF antagonist-based therapy or within 90 days after the anti-TNF agent was discontinued. We used Cox proportional hazards models to assess the association between concomitant use of immunomodulators and treatment ineffectiveness. Results: In patients with CD, combination therapy was associated with a significant decrease in likelihood of treatment ineffectiveness (adjusted hazard ratio [aHR] for ineffectiveness, 0.62; 95% CI, 0.49–0.79). However, this association was not significant in patients with UC (aHR, 0.82; 95% CI, 0.56–1.20). In patients with CD, combination therapy was also associated with increased time to first IBD-related hospitalization (aHR 0.53; 95% CI, 0.36–0.80) and switching anti-TNF agents (aHR, 0.63; 95% CI, 0.41–0.97), but not associated with IBD-related surgery (aHR, 0.76; 95% CI, 0.51–1.12) or new or recurrent use of corticosteroids (aHR, 0.75; 95% CI, 0.55–1.04). Conclusion: In an analysis of a database of real-world patients with IBD, we associated initiation therapy with a combination immune modulators and anti-TNF agents with a decreased likelihood of treatment ineffectiveness for patients with CD but not UC.

AB - Background & Aims: Although guidelines recommend inclusion of immune modulators in anti-tumor necrosis factor (TNF) initiation therapy for Crohn's disease (CD) or ulcerative colitis (UC), there are limited data on the incremental effectiveness of this treatment strategy from the real world. Methods: We collected data from the Manitoba Inflammatory Bowel Disease (IBD) Epidemiology database on persons with CD (n=852) or UC (n=303), from 2001 through 2016, who began treatment with a TNF antagonist. New and/or continuing users of immunomodulators at the time anti-TNF therapy began were considered recipients of combination therapy. The main outcome was treatment ineffectiveness (IBD-related hospitalization, intestinal resection, corticosteroid use, or change of anti-TNF agent) during TNF antagonist-based therapy or within 90 days after the anti-TNF agent was discontinued. We used Cox proportional hazards models to assess the association between concomitant use of immunomodulators and treatment ineffectiveness. Results: In patients with CD, combination therapy was associated with a significant decrease in likelihood of treatment ineffectiveness (adjusted hazard ratio [aHR] for ineffectiveness, 0.62; 95% CI, 0.49–0.79). However, this association was not significant in patients with UC (aHR, 0.82; 95% CI, 0.56–1.20). In patients with CD, combination therapy was also associated with increased time to first IBD-related hospitalization (aHR 0.53; 95% CI, 0.36–0.80) and switching anti-TNF agents (aHR, 0.63; 95% CI, 0.41–0.97), but not associated with IBD-related surgery (aHR, 0.76; 95% CI, 0.51–1.12) or new or recurrent use of corticosteroids (aHR, 0.75; 95% CI, 0.55–1.04). Conclusion: In an analysis of a database of real-world patients with IBD, we associated initiation therapy with a combination immune modulators and anti-TNF agents with a decreased likelihood of treatment ineffectiveness for patients with CD but not UC.

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Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study

Abstract

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PubMed: MeSH publication types

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