FromNEW YORK (Reuters Health) - In patients with inflammatory bowel disease (IBD), concentrations of infliximab and adalimumab varied depending on whether they were assessed with the Enzyme-Linked Immunosorbent Assay (ELISA) or the Homogeneous Mobility Shift Assay (HMSA), researchers found.
They suggest that for now, clinicians become familiar with a single assay and use that for monitoring patients.
"The importance of therapeutic drug monitoring (TDM), particularly proactive TDM, is becoming increasingly recognized," Dr. Adam Cheifetz of Beth Israel Deaconess Medical Center in Boston told Reuters Health by email. "Additionally, there are more commercially available assays to measure drug concentrations."
Dr. Cheifetz and colleagues prospectively collected and compared paired samples from 75 patients with IBD - 45 on infliximab and 30 on adalimumab - using ELISA (Inform Diagnostics, sponsor of the study) and HMSA (Prometheus Laboratories).
"Concentrations for both drugs were significantly higher when measured with HMSA compared to ELISA," he said. "Though there was good correlation between the assays, agreement between (them) was weak."
As reported online September 27 in Inflammatory Bowel Diseases, median infliximab concentrations were 12.6 mcg/mL when measured by HMSA versus 5.7 mcg/mL with ELISA; the pattern was similar for measurement of adalimumab concentrate ions (median 19.9 mcg/mL vs. 10.3 mcg/mL
As Dr. Cheifetz noted, there was a good correlation for infliximab (correlation coefficient = 0.861) and adalimumab (r = 0.935), although agreement between assays was weak.
Qualitative agreement in infliximab concentration status (therapeutic or subtherapeutic) was lacking between assays using >5 mcg/mL, >7 mcg/mL, or >10 mcg/mL as therapeutic drug concentrations.
By contrast, qualitative agreement in adalimumab concentration status was moderate between assays using either >5 or >7 mcg/mL as therapeutic drug concentrations; however, there was no agreement using >10 mcg/mL as the therapeutic drug concentration.
"This study raises the need for cross-validation of all TDM assays so clinicians will be able to better interpret TDM results, avoid misclassification of patients, and provide optimal patient care," the authors state. For now, "it is advised that clinicians become familiar with a single assay and repeatedly monitor their patients with the same assay."
Dr. Cheifetz said, "Based on the results of this study, presented at national meetings, Prometheus Laboratories initiated a comprehensive review of their assays and found an upward drift for their infliximab and adalimumab assays over a two-year period, including when our study was being performed. Prometheus corrected the errant values and reported the revised drug concentrations to physicians."
"According to Prometheus," he said, "12.5% of tests changed clinical thresholds as defined by the American Gastroenterological Association guidelines."
Dr. Jordan Axelrad, a gastroenterologist and assistant professor of medicine at NYU Langone's IBD Center, said in an email to Reuters Health, "Previous studies have suggested that ELISA testing may underestimate serum drug concentrations compared to HMSA testing."
Like the authors, he noted, "Good correlation exists between the assays that measure drug, but the absolute concentrations may differ across tests. As such, it is not unusual to receive different drug concentration results based on different laboratory assays."
"In my clinical practice," he said, "I tend to favor TDM testing with broader insurance coverage, which are generally ELISA tests. Using the same assay allows providers to compare absolute concentrations in a particular patient over time and apply the results to clinical changes."
The study was funded by Inform Diagnostics Inc
In patients with inflammatory bowel disease (IBD), concentrations of infliximab and adalimumab varied depending on whether they were assessed with the Enzyme-Linked Immunosorbent Assay (ELISA) or the Homogeneous Mobility Shift Assay (HMSA), researchers found.