Crohn Disease: When Infliximab Fails, a Customized Algorithm May Succeed

August 20, 2013

In Crohn disease patients, the algorithm evaluates infliximab bioavailability (serum levels) and immunogenicity (antibody testing)to guide further treatment.

Loss of clinical effect for infliximab (IFX) is common in patients with Crohn disease-current 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 study-a randomized, single-blind trial of 69 patients with secondary IFX failure-compared 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 the December 2012 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 such as IFX and other immunomodulators (our coverage, here and here). Last month, we reviewed an adalimumab study suggesting that careful follow-up with serial C-reactive protein levels could predict which patients needed more aggressive therapy with adalimumab. The current study joins the chorus-treatment guided by this Danish algorithm, based on 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 use 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 tested-algorithms tend to be fluid in academic health science centers and it’s rare to see one become standardized and widely tested. That’s probably a loss, but despite that, expect to see more algorithm-driven medication use in inflammatory bowel disease, all of it fueled by aggressive 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 Crohn’s disease who lose response to anti-TNF treatment: a randomized, controlled trial. Gut. July 2013, published online. (Abstract