Crohn's Disease Treatment Dose-Escalation Rates Below Estimates, Prompts Further Examination

Examining infliximab dose escalation rates could help maximize cost-benefit treatment algorithms.

Infliximab dose escalation rates in patients with Crohn’s disease are at the lower range of published estimates, according to the results of a study published in the April 2014 edition of American Health and Drug Benefits.

The findings may support a reexamination of dose escalation in cases where it makes treatment more effective, the researchers noted. Additional studies with larger sample sizes are needed, however.

“It may also be worth reexamining the concept of dose escalation, because many patients who require higher doses of infliximab during the course of treatment may be better described as ‘dose optimized’ if treatment effectiveness is achieved and maintained at the higher dose,” the researchers wrote. “This may also serve to remove the negative connotations associated with dose escalation.”

Janssen Scientific Affairs provided funding for the study, although it did not participate in the data management or analysis.

The FDA’s approved dosing for infliximab inductions is 5mg per kilogram of weight at weeks 0, 2, and 6, followed by maintenance infusions at that dose every 8 weeks. Clinicians have the option of increasing the dose up to 10 mg per kilogram of weight on the same schedule, however. Dose escalation can involve either increases in infusion frequency or larger doses of the treatment.

Researchers collected managed care organization participant data retrospectively from administrative claims and medical charts from 2006 to 2011. Physicians received $500 for agreeing to participate in the study, and an additional $50 for every medical chart that met eligibility criteria.

The data revealed 110 participants who received at least 4 therapy infusions, although 4 participants were subsequently excluded due to missing dose and interval data, for a total cohort of 106 participants. Participants received an average of 6.7 infusions.

Only 18 participants (17%) showed evidence of dose escalation. Nine showed shorter intervals between therapy doses, and 12 showed increases in the dosage received. Three additional patients showed both an increase in dosage and a more frequent treatment interval.

Participants whose infliximab dose was escalated tended to have a shorter length of therapy, receiving 257 days of therapy to the 333 days of therapy seen in participants receiving stable infliximab doses.

Most of the participants examined were in the maintenance phase of treatment, regardless of whether their infliximab dose changed or remained stable.

“This type of evidence can facilitate the development of management algorithms that maximize the cost-benefit of therapies for the treatment of Crohn’s disease,” the researchers wrote. “In an attempt to further reduce waste, managed care organizations may seek to reduce the number of failed trials of expensive therapeutics and begin modeling algorithms that better match patients to a therapy and reduce the probability of treatment failure.”