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Proactive Humira monitoring improves outcomes in pediatric Crohn’s
For pediatric patients with Crohn’s disease, proactive monitoring of Humira trough concentrations and dose adjustments improved rates of corticosteroid-free clinical remission.
Amit Assa , MD, MHA, of Schneider Children’s Medical Center of Israel, and colleagues wrote that therapeutic drug monitoring (TDM) is a common method to address loss of response during anti-TNF therapy, and treatment can be guided by either reactive or proactive strategies.
“Based on current data, it is appealing to speculate that tailored treatment, based on routine [trough concentrations (TC)] and antibodies measurements (proactive TDM), may assist in sustaining adequate drug levels, thus, improving efficacy and preventing the evolution of anti-drug antibodies,” the researchers wrote. “To date, there are no prospective studies comparing proactive vs. reactive TDM in pediatric CD, nor studies evaluating this approach among adults or children treated with [Humira (adalimumab, AbbVie)].”
Researchers performed a non-blinded, randomized controlled trial comprising 78 children with CD (mean age, 14.3±2.6 years; 29% girls) who had no previous biologic use but had responded to adalimumab induction therapy. They randomly assigned patients to receive either proactive TDM (measuring trough concentrations at week 4 and 8 and every 8 weeks until week 72; n = 38) or reactive TDM (informed physicians about trough concentrations after loss of response; n = 40). The study’s primary endpoint was sustained corticosteroid-free remission at all visits from week 8 to week 72.
Investigators found that 31 children in the proactive TDM group achieved the primary endpoint compared with 19 in the reactive group (82% vs. 48%; P = .002). A larger proportion of patients in the proactive group also achieved a composite outcome of sustained corticosteroid-free remission, C-reactive protein levels of 0.5 mg/dL or less and fecal calprotectin levels of 150 µg/g or less compared with 5 patients in the reactive group (42% vs. 12%; P = .003).
At the end of the study, 33 patients in the proactive TDM group received dose intensification compared with 24 patients in the reactive TDM group (87% vs. 60%; P = .001).
“The study, the first of its kind performed in the pediatric population, shows that proactive trough measurement is superior to reactive measurements, resulting in higher corticosteroid-free sustained remission and biologic remission rates,” Assa and colleagues concluded. – by Alex Young
Disclosures: Assa reports receiving consulting and lecture fees from AbbVie and research grants from AbbVie and Janssen. Please see the full study for all other authors’ relevant financial disclosures.
Perspective
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This is the first prospective study to demonstrate that proactive therapeutic drug monitoring (TDM) is more effective than standard dosing of anti-TNF therapies. In this long-awaited study, Assa and colleagues showed that in a group of biologic-naive pediatric patients with Crohn’s disease that proactive TDM performed early in the course of adalimumab improved steroid-free remission rates at all visits from week 8 to 72 (primary endpoint) compared with reactive TDM.
Further, secondary endpoints that included objective measures of inflammation also favored the proactive TDM group. Though the study was not blinded and did not include an endoscopic endpoint, it was a huge step forward in the field of TDM and added credence to the utility of proactive TDM compared with the standard of care. Additionally, it demonstrated that current dosing strategies under dosed most patients in both groups; 87% in the proactive group and 60% in the reactive group required dose optimization.
Previously, many association studies in IBD and other immune-mediated inflammatory disorders have shown that higher serum biologic drug concentrations are associated with better therapeutic outcomes. Proactive TDM, defined as the measurement of serum trough concentrations with and dosing to a threshold drug concentration, has been previously shown to be better than empiric drug optimization and/or reactive TDM of anti-TNF.
However earlier studies were either retrospective or secondary outcomes from prospective studies. These studies did demonstrate that proactive TDM was associated with greater drug persistence of adalimumab and infliximab as well as improved more objective outcomes, including decreased IBD-related hospitalization and surgery rates in patients on infliximab. This prospective study in patients with pediatric Crohn’s disease adds a great deal of evidence to the effectiveness of proactive TDM.
References
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- Papamichael K, et al. J Crohns Colitis. 2019;doi:10.1093/ecco-jcc/jjz018.
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