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; Aruni 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

Clin Gastroenterol Hepatol. 2019 Aug;17(9):1788-1798.e2. doi: 10.1016/j.cgh.2018.11.003. Epub 2018 Nov 15.

Authors

Affiliations

¹ Section of Gastroenterology, Division of Internal Medicine, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: laura.targownik@med.umanitoba.ca.
² Children's Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
³ Section of Gastroenterology, Division of Internal Medicine, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
⁴ Section of Gastroenterology, Division of Internal Medicine, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Community Health Sciences, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
⁵ Department of Community Health Sciences, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
⁶ Arthritis Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
⁷ Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
⁸ Department of Internal Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
⁹ The Ottawa Hospital IBD Centre, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹⁰ Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
¹¹ Department of Community Health and Epidemiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

PMID: 30448599
DOI: 10.1016/j.cgh.2018.11.003

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.

Keywords: Combined; Management; Thiopurines; Treatment Comparison.

Publication types

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

MeSH terms

Adalimumab / therapeutic use
Adult
Azathioprine / therapeutic use
Cohort Studies
Colitis, Ulcerative / drug therapy*
Colitis, Ulcerative / surgery
Crohn Disease / drug therapy*
Crohn Disease / surgery
Digestive System Surgical Procedures / statistics & numerical data
Drug Substitution
Drug Therapy, Combination
Female
Glucocorticoids / therapeutic use
Hospitalization / statistics & numerical data
Humans
Immunologic Factors / therapeutic use*
Inflammatory Bowel Diseases / drug therapy
Infliximab / therapeutic use
Male
Manitoba
Methotrexate / therapeutic use
Prednisone / therapeutic use
Proportional Hazards Models
Retrospective Studies
Tumor Necrosis Factor Inhibitors / therapeutic use*

Substances

Glucocorticoids
Immunologic Factors
Tumor Necrosis Factor Inhibitors
Infliximab
Adalimumab
Azathioprine
Prednisone
Methotrexate