Letter: dry blood spots for anti-TNF treatment monitoring in IBD



As nicely reviewed by Chaparro et al.,[1] therapeutic drug monitoring (TDM) of anti-tumour necrosis factor (TNF)-alpha monoclonal antibodies with drug level determinations at regular intervals holds the potential for predicting treatment failure and sustained response in inflammatory bowel disease patients. The currently ongoing TAXIT trial will show whether the long-term adjustment of the treatment based on infliximab levels is superior to the empiric approach.[2]

An easy system of blood sampling, combined with an accessible analysis method, would allow peak and intermediate drug level determinations. Using population pharmacometric analyses, an ideal trough level (window) could be predicted which would allow for dose-to-target adaptations to increase the efficacy and safety of anti-TNF treatment. We propose here an easy method via capillary puncture and dry blood spot (DBS) that avoids impracticalities associated with conventional venous sampling (e.g. extra hospital visits, processing of blood, shipment of serum, etc.) and which costs less.[3]

The advantages of DBS have already been recognised for use in preclinical and clinical pharmacokinetic studies with many small molecules.[4] Ideally, an extraction method should be developed to elute the biopharmaceutical from the sampling paper after which the eluent can be analysed using an established method (e.g. ELISA) (Figure 1).[5] To exploit the full potential of DBS, stability at different conditions should be tested and the extraction and detection method should be insensitive to the volume spotted (above a certain threshold). It is not required to have 100% recovery of the analyte for TDM (if a recalculation factor is used) as long as the extent of recovery is consistent, precise and reproducible within a concentration range (e.g. a range from 0.3 to 100 μg/mL would seem appropriate for infliximab).[3]

Figure 1.

Optimisation and validation of a dry blood spot method for therapeutic drug monitoring of anti-tumour necrosis factor-alpha biopharmaceuticals.

Within this range, the accuracy should lie within the predefined limits of 80–120% and the precision should not exceed 15%, except for the lower limit of quantification where it should not exceed more than 20%. In addition, blood from patients with different haematocrit levels should be investigated, as well as the impact of anti-drug antibodies on the detection of drug. To rule out errors associated with this new technique, a thorough validation is needed but we believe that it constitutes a major advantage of intermediate sampling (in between scheduled hospital visits) which is patient-friendly and would allow immediate intervention at the next dosing.


Declaration of personal interests: N.V.C., S.B. and P.D. have no conflict of interests. M.F. has served as a speaker for Abbott, Janssen, MSD, Ferring, Chiesi and Tillots and as a consultant for Abbott, Janssen and MSD. P.R. has served as a speaker and a consultant for Centocor, Merck and Abbott and has received research funding from UCB, Centocor, Merck and Abbott. S.V. has served as a speaker for UCB, Abbott, MSD, Ferring, Centocor and Chiesi and has received research funding from Abbott, Centocor, MSD and UCB. A.G. has served as a speaker for Pfizer and MSD and has received research funding from Pfizer.

Declaration of funding interests: This study was funded in part by the Fund for Scientific Research-Flanders, grant number G.0617.12.