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Crohn Disease: When Infliximab Fails, a

Customized Algorithm May Succeed
By Jeffrey Hertzberg, MD, MS | August 20, 2013
Jeffrey Hertzberg, MD, MS is Assistant Professor at the University of Minnesotas Medical Industry
Leadership Institute, and President of Medformatics, Inc., a consultancy specializing in the design and
implementation of health care information systems and the interpretation of large medical data sets.
Loss of clinical effect for (IFX) is common in patients with infliximab(Drug information on infliximab)
Crohn diseasecurrent guidelines recommend an increase in IFX dose in response. This has been identified
as an expensive and often suboptimal strategy because individual patient pharmacodynamics make response
to dose intensification unpredictable. Dose intensification also risks a long delay before therapeutic effect is
regained. A new Danish studya randomized, single-blind trial of 69 patients with secondary IFX
failurecompared the efficacy and cost of dose intensification versus an algorithm-driven individualized
treatment strategy based on IFX bioavailability and pharmacodynamics. The results were published online
ahead of print on July 22, 2013 in the journal . Gut
At December 2012s Advances in Inflammatory Bowel Disease conference, speakers stressed the need to
individualize therapy based on treatment response and aggressive drug monitoring when using anti-tumor
necrosis factor (anti-TNF) drugs like IFX and other immunomodulators (our coverage, and . Last here here)
month, we reviewed an suggesting that careful follow-up with serial C-reactive protein adalimumab study
levels could predict which patients needed more aggressive therapy with adalimumab(Drug information on
. The current study joins the chorustreatment guided by this Danish algorithm, based on adalimumab)
careful evaluation of IFX bioavailability (by serum levels) and immunogenicity (by antibiody testing), was
less expensive yet equally effective when compared with unguided increases in IFX dose for Crohn disease
patients who no longer experienced therapeutic effect.
Anti-TNF biopharmaceuticals, now used in multiple chronic inflammatory diseases, have become one of the
most important drivers of pharmacy costs in the United States. This study found decreased cost of treatment
(but not superior efficacy) in the study arm managed with the algorithm. The algorithm-customized regimen
could be a safer strategy, because some subjects managed by algorithm were switched off anti-TNFs
altogether and put on conventional immunosuppressive agents, which have a better safety profile. Others
were switched to a different anti-TNF, so only a fraction of the subjects were given intensified IFX treatment
(those with insufficient IFX bioavailability due to non-immune mediated pharmacokinetics).
The study looked at all costs of inpatient and outpatient treatment, so if decreased utilization of IFX was
translating into higher hospital costs, the methodology would have detected it. The crucial limitation here is
the size of the study, with only 69 subjects, yet it may never be replicated on a larger scale, given the
specificity of the algorithm being testedalgorithms tend to be fluid in academic health science centers and
its rare to see one become standardized and widely tested. Thats probably a loss, but despite that, expect to
see more algorithm-driven medication use in inflammatory bowel disease, all of it fueled by aggressive
ConsultantLive.com. Vol. No. August 20, 2013
http://www.consultantlive.com/gastrointestinal-disorders/content/article/10162/2154673
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monitoring of serum levels and immunogenicity.
Steenholdt C, Brynskov J, Thomsen OO, et al. Individualised therapy is more cost-effective than dose
intensification in patients with Crohns disease who lose response to anti-TNF treatment: a randomized,
controlled trial. . 2013 (July), published online. ( ) Gut Abstract
ConsultantLive.com. Vol. No. August 20, 2013
http://www.consultantlive.com/gastrointestinal-disorders/content/article/10162/2154673
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