The benefit of combination therapy depends on disease phenotype and duration in Crohn's disease

A. N. Ananthakrishnan, A. Sakuraba, E. L. Barnes, J. Pekow, Laura E. H. Raffals, M. D. Long, R. S. Sandler

Research output: Contribution to journalArticle

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Abstract

Background: The impact of combination therapy on disease-related morbidity in patients with established Crohn's disease (CD) or ulcerative colitis (UC) remains to be well-defined. Aim: To examine the effect of combination therapy on disease outcomes in CD and UC. Methods: Using a multicenter prospective cohort, we classified CD and UC patients as being on monotherapy with anti-TNF or on combination with an immunomodulator. The primary outcome was a composite of new IBD-related surgery, hospitalisations, penetrating complications, need for corticosteroids or new biological at 1 year. Multivariable regression models adjusted for potential confounders. Results: We included 707 patients with CD (45% combination therapy) and 164 with UC (38% combination therapy). Combination therapy was not associated with reduction in the composite outcome in either CD (OR: 0.87, 95% CI: 0.63-1.22) or UC (OR: 1.45, 95% CI: 0.63-3.38). However, while no difference was noted in those with nonstricturing, nonpenetrating CD, a significant reduction in the likelihood of the outcome was seen in those with stricturing or penetrating CD (30% vs 39%, OR: 0.58, 95% CI: 0.37-0.90). A stronger effect was also observed in those with disease duration <5 years (OR: 0.35, 95% CI: 0.14-0.87) compared to those with a longer duration (OR: 0.75, 95% CI: 0.45-1.27). A similar reduction in occurrence of composite outcome was noted with infliximab and with other anti-TNF biologics. Conclusion: The benefit of combination immunomodulator-biological therapy is stronger in those with complicated Crohn's disease, particularly early on in their disease course.

Original languageEnglish (US)
Pages (from-to)162-168
Number of pages7
JournalAlimentary Pharmacology and Therapeutics
Volume46
Issue number2
DOIs
StatePublished - Jul 1 2017

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Crohn Disease
Phenotype
Ulcerative Colitis
Immunologic Factors
Therapeutics
Biological Therapy
Biological Products
Adrenal Cortex Hormones
Hospitalization
Morbidity

ASJC Scopus subject areas

  • Pharmacology (medical)

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The benefit of combination therapy depends on disease phenotype and duration in Crohn's disease. / Ananthakrishnan, A. N.; Sakuraba, A.; Barnes, E. L.; Pekow, J.; Raffals, Laura E. H.; Long, M. D.; Sandler, R. S.

In: Alimentary Pharmacology and Therapeutics, Vol. 46, No. 2, 01.07.2017, p. 162-168.

Research output: Contribution to journalArticle

Ananthakrishnan, A. N. ; Sakuraba, A. ; Barnes, E. L. ; Pekow, J. ; Raffals, Laura E. H. ; Long, M. D. ; Sandler, R. S. / The benefit of combination therapy depends on disease phenotype and duration in Crohn's disease. In: Alimentary Pharmacology and Therapeutics. 2017 ; Vol. 46, No. 2. pp. 162-168.
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abstract = "Background: The impact of combination therapy on disease-related morbidity in patients with established Crohn's disease (CD) or ulcerative colitis (UC) remains to be well-defined. Aim: To examine the effect of combination therapy on disease outcomes in CD and UC. Methods: Using a multicenter prospective cohort, we classified CD and UC patients as being on monotherapy with anti-TNF or on combination with an immunomodulator. The primary outcome was a composite of new IBD-related surgery, hospitalisations, penetrating complications, need for corticosteroids or new biological at 1 year. Multivariable regression models adjusted for potential confounders. Results: We included 707 patients with CD (45{\%} combination therapy) and 164 with UC (38{\%} combination therapy). Combination therapy was not associated with reduction in the composite outcome in either CD (OR: 0.87, 95{\%} CI: 0.63-1.22) or UC (OR: 1.45, 95{\%} CI: 0.63-3.38). However, while no difference was noted in those with nonstricturing, nonpenetrating CD, a significant reduction in the likelihood of the outcome was seen in those with stricturing or penetrating CD (30{\%} vs 39{\%}, OR: 0.58, 95{\%} CI: 0.37-0.90). A stronger effect was also observed in those with disease duration <5 years (OR: 0.35, 95{\%} CI: 0.14-0.87) compared to those with a longer duration (OR: 0.75, 95{\%} CI: 0.45-1.27). A similar reduction in occurrence of composite outcome was noted with infliximab and with other anti-TNF biologics. Conclusion: The benefit of combination immunomodulator-biological therapy is stronger in those with complicated Crohn's disease, particularly early on in their disease course.",
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AU - Ananthakrishnan, A. N.

AU - Sakuraba, A.

AU - Barnes, E. L.

AU - Pekow, J.

AU - Raffals, Laura E. H.

AU - Long, M. D.

AU - Sandler, R. S.

PY - 2017/7/1

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N2 - Background: The impact of combination therapy on disease-related morbidity in patients with established Crohn's disease (CD) or ulcerative colitis (UC) remains to be well-defined. Aim: To examine the effect of combination therapy on disease outcomes in CD and UC. Methods: Using a multicenter prospective cohort, we classified CD and UC patients as being on monotherapy with anti-TNF or on combination with an immunomodulator. The primary outcome was a composite of new IBD-related surgery, hospitalisations, penetrating complications, need for corticosteroids or new biological at 1 year. Multivariable regression models adjusted for potential confounders. Results: We included 707 patients with CD (45% combination therapy) and 164 with UC (38% combination therapy). Combination therapy was not associated with reduction in the composite outcome in either CD (OR: 0.87, 95% CI: 0.63-1.22) or UC (OR: 1.45, 95% CI: 0.63-3.38). However, while no difference was noted in those with nonstricturing, nonpenetrating CD, a significant reduction in the likelihood of the outcome was seen in those with stricturing or penetrating CD (30% vs 39%, OR: 0.58, 95% CI: 0.37-0.90). A stronger effect was also observed in those with disease duration <5 years (OR: 0.35, 95% CI: 0.14-0.87) compared to those with a longer duration (OR: 0.75, 95% CI: 0.45-1.27). A similar reduction in occurrence of composite outcome was noted with infliximab and with other anti-TNF biologics. Conclusion: The benefit of combination immunomodulator-biological therapy is stronger in those with complicated Crohn's disease, particularly early on in their disease course.

AB - Background: The impact of combination therapy on disease-related morbidity in patients with established Crohn's disease (CD) or ulcerative colitis (UC) remains to be well-defined. Aim: To examine the effect of combination therapy on disease outcomes in CD and UC. Methods: Using a multicenter prospective cohort, we classified CD and UC patients as being on monotherapy with anti-TNF or on combination with an immunomodulator. The primary outcome was a composite of new IBD-related surgery, hospitalisations, penetrating complications, need for corticosteroids or new biological at 1 year. Multivariable regression models adjusted for potential confounders. Results: We included 707 patients with CD (45% combination therapy) and 164 with UC (38% combination therapy). Combination therapy was not associated with reduction in the composite outcome in either CD (OR: 0.87, 95% CI: 0.63-1.22) or UC (OR: 1.45, 95% CI: 0.63-3.38). However, while no difference was noted in those with nonstricturing, nonpenetrating CD, a significant reduction in the likelihood of the outcome was seen in those with stricturing or penetrating CD (30% vs 39%, OR: 0.58, 95% CI: 0.37-0.90). A stronger effect was also observed in those with disease duration <5 years (OR: 0.35, 95% CI: 0.14-0.87) compared to those with a longer duration (OR: 0.75, 95% CI: 0.45-1.27). A similar reduction in occurrence of composite outcome was noted with infliximab and with other anti-TNF biologics. Conclusion: The benefit of combination immunomodulator-biological therapy is stronger in those with complicated Crohn's disease, particularly early on in their disease course.

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