Adverse events do not outweigh benefits of combination therapy for Crohn's disease in a decision analytic model.

Abstract

BACKGROUND & AIMS:

The Study of Biologic and Immunomodulator-Naïve Patients With Crohn's Disease (SONIC) showed that combination therapy with infliximab and azathioprine (IFX/AZA) is more effective than treatment with IFX alone. Numbers and types of adverse events were roughly equivalent among groups, although enrollment was limited, so it was not clear how rare adverse events might affect overall outcomes in practice. We sought to define the frequency at which a rare adverse event would have to occur for the risks of combination therapy to outweigh the benefits of treatment.

METHODS:

We constructed a decision model to compare the risks and benefits of IFX/AZA with IFX monotherapy. Model parameters were taken from SONIC and other published literature. The base-case analysis was patients with active Crohn's disease who are naïve to both medications (similar to those in SONIC) who were treated for 1 year. We used sensitivity analyses to determine the thresholds at which the risks of side effects from IFX/AZA outweigh its benefits.

RESULTS:

During 1 year, the benefits of IFX/AZA would outweigh the risks, unless serious infections occurred in 20% or more of the population or lymphoma in 3.9% or more. These thresholds are 5-fold and 65-fold higher than base-case estimates, respectively.

CONCLUSIONS:

On the basis of data from 1 year of SONIC, the combination of IFX/AZA was more effective than IFX alone in patients with Crohn's disease who are naïve to either drug. For the risks of combination therapy to outweigh the benefits in this time frame, the incidence of serious adverse events would have to be higher than seems clinically realistic.

• Authors: Corey A Siegel, Samuel R G Finlayson, Bruce E Sands, Anna N A Tosteson
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 10 Issue 1 Pg. 46-51 (Jan 2012) ISSN: 1542-7714 [Electronic] United States
• PMID: 21963958 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Immunologic Factors
• Infliximab
• Azathioprine

Topics

• Adult
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Azathioprine (administration & dosage, adverse effects)
• Crohn Disease (drug therapy)
• Decision Support Techniques
• Drug Therapy, Combination (adverse effects, methods)
• Humans
• Immunologic Factors (administration & dosage, adverse effects)
• Infliximab
• Treatment Outcome