The American Gastroenterological Association (AGA) has issued official recommendations on therapeutic drug monitoring (TDM) for inflammatory bowel disease (IBD). The full document also contains a Technical Review, which includes clinical data that helped form the recommendations.
Immunomodulators and/or biologics are commonly used to treat IBD. To optimize drug concentration and improve outcomes, TDM is used to check the trough concentration and evaluate for the presence of anti-drug antibodies. The Committee developed these guidelines to “inform appropriate utilization of TDM with anti-tumor necrosis factor (TNF)-α agents and thiopurines.” The recommendations also help establish the role of testing the genetic or enzymatic activity of thiopurine methyltransferase (TPMT) prior to starting thiopurine therapy.
The guidelines, however, do not include TDM recommendations for patients treated with vedolizumab or ustekinumab due to insufficient data.
The AGA has developed the following five major recommendations for TDM in IBD including the strength of recommendation and quality of evidence.
In adults with active IBD treated with anti-TNF agents, the AGA suggests reactive therapeutic drug monitoring to guide treatment changes. (Conditional recommendation; very low quality of evidence). For patients on maintenance therapy for active IBD, the suggest target trough concentrations for the anti-TNF agents are as follows:
- Infliximab: ≥5μg/mL
- Adalimumab: ≥7.5μg/mL
- Certolizumab pegol: ≥20μg/mL
- Golimumab: unknown
The optimal trough concentrations for induction therapy are uncertain.
In adult patients with quiescent IBD treated with anti-TNF agents, the AGA makes no recommendation regarding the use of routine proactive therapeutic drug monitoring. (No recommendation; knowledge gap). Selective TDM among these patients may produce a benefit but there is concern for harm with switching from index therapy too early. The current data supporting proactive and routine TDM is lacking and the benefits of this strategy remain uncertain.
In adult patients with IBD being started on thiopurines, the AGA suggests routine TPMT testing (enzymatic activity or genotype) to guide thiopurine dosing. (Conditional recommendation; low quality). Moreover, the panel recommends routine lab testing, including complete blood count (CBC), no matter the TMPT testing results. Although existing evidence suggests there may not be much benefit with this method vs. empiric weight-based dosing, a small patient subgroup who are homozygous for TPMT “are at risk for considerable harm due to severe neutropenia and infections, if treated with empiric weight-based dosing.”
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. (Conditional recommendation; very low quality). In patients with active IBD-related symptoms, the panel suggests a target 6-thioguanine (6-TGN) cutoff between 230 and 450pmol/8×10^8 red blood cells (RBCs) when used as monotherapy; these levels were tied to 40% higher rates of remission vs. levels <230pmol/8×10^8 RBCs. When used in combination with anti-TNF therapies however, the optimal 6-TGN cutoff is unclear.
In adult patients with quiescent IBD treated with thiopurines, the AGA suggests against routine thiopurine metabolite monitoring. (Conditional recommendation; very low quality). In two studies (n=107) evaluating routine thiopurine metabolite monitoring to achieve 6-TGN levels of 250 to 450pmol/8×10^8 RBCs vs. weight-based dosing by TPMT testing, the authors found no significant difference in the rate of achieving clinical remission or serious adverse events.
The expert panel concluded that more studies are needed to charaterize clinically meaningful versus insignificant anti-drug antibodies, and at which levels can these antibodies be suppressed before there is a need for treatment change. The use of TDM to help optimize newer biologic agents will also need to be investigated.
For more information visit gastrojournal.org.