Symptoms sufficient to prompt infliximab-dose increases in Crohn's disease

Last Updated: 2018-01-26

By Reuters Staff

NEW YORK (Reuters Health) - Symptoms alone are as useful as a combination of symptoms, biomarkers and serum drug concentrations for determining the need for an increased dose of infliximab in patients with Crohn's disease (CD), according to results from a randomized trial.

Low serum concentrations of anti-tumor necrosis factor (TNF) agents and/or the development of anti-drug antibodies are associated with impaired clinical efficacy, reduced mucosal healing and loss of clinical response in patients with CD. How best to adjust the dosing of anti-TNF agents remains unclear.

Dr. Geert D'Haens from Academic Medical Center, in Amsterdam, and colleagues investigated whether proactive dose increases of infliximab based on symptoms, biomarkers and/or frequently measured infliximab trough level would lead to better outcomes than conventional management based on symptoms alone in their study of 122 patients with moderate to severe endoscopically active CD.

More than a quarter of patients (29%) dropped out of the trial before week 54, mainly due to lack of improvement or withdrawal of consent.

The study groups did not differ in the cumulative incidence of first infliximab intensification through the end of the one-year trial, and only a minority of patients were dose-escalated based on serum concentrations, the researchers report in Gastroenterology, online January 6.

The primary endpoint was sustained corticosteroid-free clinical remission from weeks 22 through 54 with no ulcers at week 54. This was reached by a similar fraction of patients whose dose increases (steps of 2.5 mg/kg, or an increase from 5 to 10 mg/kg) were based on clinical symptoms, biomarker analysis, and/or serum infliximab concentrations (33% and 27%, respectively) and by those whose dose increases were based on clinical symptoms alone (40%; P=0.50).

Moreover, the groups did not differ significantly in their rates of endoscopic remission or significant endoscopic improvement.

Sustained infliximab serum concentrations above 3 micrograms/mL were achieved by similar proportions of patients in the three treatment groups, and antibodies to infliximab were detected in similar proportions of patients in the three groups at the end of the trial.

Adverse event and serious adverse event rates were also similar across the groups.

"In conclusion, dose increase of infliximab for active CD based on a combination of symptoms, biomarkers, and serum concentrations was not superior to dose increase based on symptoms alone, although the study was not designed nor powered to determine superiority of therapeutic drug monitoring (TDM)," the researchers conclude. "This trial underscores the difficulty to perform 'pure TDM' trials when dose escalation of biologics is part of clinical practice."

Merck Sharp Dome and Janssen supported the trial, and Prometheus laboratories performed measurements of anti-infliximab antibodies. Nine of the 26 authors had various relationships with one or more of these companies.

Dr. D'Haens did not respond to a request for comment.

SOURCE: http://bit.ly/2rDpt9L

Gastroenterology 2018.