Yazarlar : The Benefit to Risk Balance of Combining Infliximab with Azathioprine Varies With Age: A Markov Model

Yayın : Scott F, Vajravelu R, Bewtra M et al

Yayın Yılı : 2014

Pubmed Linki : http://www.docguide.com/benefit-risk-balance-combining-infliximab-azathioprine-varies-age-markov-model?tsid=5

Konu : Lenfoma

Literatür İçeriği :  BACKGROUND & AIMS Combination therapy with infliximab and azathioprine has demonstrated benefit over monotherapy for moderate-to-severe Crohn's Disease. Clinical trials and models have not accounted for age-specific risks associated with these therapies, including the risk of immunosuppression-related cancer and infection. After accounting for these risks, the strategy yielding the greatest benefit may vary with age.

METHODS We assessed age-specific risks and benefits of combination therapy compared to infliximab monotherapy using Markov modeling. The base case was a 35 year-old male patient with a 1-year time horizon. We assumed the incidence of lymphoma to be 5.28-fold higher with combination therapy. Secondary analyses accounted for life expectancy, therapy beyond 1 year, and age-specific surgical and infection risks. Quality-adjusted life years (QALYs) were calculated for 25-75-years old individuals.

RESULTS Combination therapy was found to be of greater benefit in the base case (0.7522 QALYs for combination therapy vs 0.7426 QALYs for monotherapy). Accounting for life years lost, monotherapy was the best approach if the hazard ratio for lymphoma with combination therapy was>8.1 patients 75 years old. Monotherapy provided greater net benefit to patients 55, 65, or 75 years old if therapy was extended for 9, 7, or 5 years, respectively. For 25 year-old men, monotherapy resulted in fewer deaths but only yielded greater QALYs if the annual incidence of hepatosplenic T-cell lymphoma exceeded 36/100,000 persons.

CONCLUSION After accounting for age-specific risks of lymphoma, infection, and surgical complications, benefits of combination therapy outweighed the risks as a short-term and intermediate-term strategy for most patients with moderate-to-severe Crohn's Disease younger than 65 years. For young male patients, combination therapy yields greater QALYs, but at cost of an increased risk of death from lymphoma.

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