By Anne Harding
NEW YORK (Reuters Health) - 25/6/2019
Proactive therapeutic-drug monitoring (TDM) in children with Crohn's disease on adalimumab reduces clinical exacerbations compared to reactive TDM, a randomized controlled trial shows.
Nearly three-quarters of the patients in the study required adalimumab intensification during treatment, suggesting that standard dosing is likely inadequate, Dr. Amit Assa of Schneider Children's Hospital in Petach-Tikva, Israel, the study's first author, told Reuters Health by email.
Monitoring drug trough concentrations and anti-drug antibodies proactively, rather than reactively after a patient stops responding to the drug, could improve treatment efficacy, Dr. Assa and his colleagues note in Gastroenterology, online June 10.
They randomly assigned 78 CD patients aged 6 to 18 who had responded to adalimumab induction therapy to proactive or reactive monitoring, with a threshold of 5 ug/mL.
In the proactive-TDM group, adalimumab trough concentrations, C-reactive protein and fecal calprotectin were measured at week four, week eight and every eight weeks until week 72. For patients in the reactive-monitoring group, physicians were informed of trough drug concentrations after patients stopped responding.
Thirty-one children (82%) in the proactive-monitoring group achieved the study's primary endpoint of sustained corticosteroid-free clinical remission at all visits from week 8 to week 72, versus 19 (48%) of the reactive-monitoring group (P=0.002).
Sixteen (42%) achieved the composite outcome of sustained remission, C-reactive protein of 0.5 mg/dL or lower and fecal calprotectin of 150 ug/g, compared to five patients (12%) in the reactive-monitoring group (P=0.003).
By week 72, 33 patients (87%) in the proactive-monitoring group and 24 patients in the reactive-monitoring group (60%) had adalimumab intensification (P=0.001).
Dr. Assa noted that current literature suggests a trough adalimumab target of 10 ug/ml, which means that almost all of their patients "would have been intensified."
"Another way to say that is that according to the standard label of adalimumab ( 40 mg every other week) we underdose most of our patients," he said.
He added, "There are two possible approaches which should be adopted in order to tackle this problem: early proactive TDM measurement and subsequent optimization or changing our practice to a more intensified regimen upfront."
Proactive monitoring is likely to be cost effective, because it prevents flares, reduces lost work days and hospitalization, and prevents patients from needing to be switched to more expensive drugs, Dr. Assa said.
"More importantly, this is better medicine," he added. "I think that TDM measurement during remission should become a standard of care as it is doesn't make sense to administer a medication 'blindly' when TDM is available, particularly now that this approach was shown to increase treatment efficacy. In general, the first TDM measurement should happen early, immediately following induction, to allow early optimization of treatment for reducing the risk of disease flare."
The study was supported by AbbVie, which sells adalimumab. Dr. Assa and several of his coauthors reported financial ties to the company.