By Reuters Staff
NEW YORK (Reuters Health) - The American Gastroenterological Association (AGA) conditionally recommends reactive therapeutic drug monitoring (TDM) to guide treatment changes in adults with active inflammatory bowel disease (IBD) treated with anti-TNF agents, in a new clinical guideline.
Dr. Joseph Feuerstein of Beth Israel Deaconess Medical Center in Boston and the guideline committee note, however, that this recommendation is based on “very low quality of evidence.” There were three observational studies and one randomized controlled trial of patients with IBD on maintenance anti-TNF therapy, they report in Gastroenterology, online August 3.
Several issues remain unresolved. “The best-available evidence did not address the optimal timing for measuring trough concentrations. In most cases, the panel recommends that a trough level for infliximab or adalimumab be drawn as close to the next dose as possible (i.e., within 24 hours). Additionally, while the drug trough concentration is consistent across different commercial assays, assays for anti-drug antibodies are not readily comparable with each other,” the committee points out.
Optimal trough concentrations for induction therapy are also uncertain, and when anti-drug antibodies are detected, it's unclear what antibody level is clinically meaningful, they note.
The AGA made no recommendation regarding the use of routine proactive TDM in adults with quiescent IBD treated with anti-TNF agents due to a “knowledge gap.”
In adults with IBD being started on thiopurines, the AGA suggests routine thiopurine methyltransferase (TPMT) testing (enzymatic activity or genotype) to guide thiopurine dosing. They say routine laboratory monitoring, including complete blood count, should be performed, regardless of TPMT testing results. This is a conditional recommendation based on “low-quality” evidence.
In adult patients treated with thiopurines with active IBD or adverse effects thought to be due to thiopurine toxicity, the AGA suggests reactive thiopurine metabolite monitoring to guide treatment changes. This is a conditional recommendation based on “very-low-quality” evidence. When measuring thiopurine metabolite monitoring in patients with active IBD-related symptoms, AGA suggests a target 6-thioguanine (6-TGN) cutoff between 230 and 450 pmol per 800 million red blood cells when used as monotherapy. They say an optimal 6-TGN cutoff when thiopurines are used in combination with anti-TNF agents is uncertain.
In adults with quiescent IBD treated with thiopurines, the AGA suggests against routine thiopurine metabolite monitoring. This conditional recommendation also is based on very-low-quality evidence.
The AGA says several knowledge gaps in TDM have been identified for which prospective observational and randomized controlled trials are warranted. They are highlighted in a Technical Review paper published with the guidelines.
SOURCES: http://bit.ly/2vTmY3t and http://bit.ly/2wxSXnP