Background: Preventing loss of response to golimumab, an anti-tumour necrosis factor (TNF) biologic, is a challenge for clinicians treating patients with ulcerative colitis (UC). Although drug serum concentrations and anti-drug antibody serum concentrations have suggested an association between golimumab exposure and clinical outcome, detailed information on absorption, distribution and elimination of the drug in a real-life cohort of patients is lacking. Dry blood spot (DBS) sampling involves a finger prick to apply whole blood to a sampling paper after which drug is extracted. We wanted to study if golimumab efficacy can be increased by exploring its full pharmacokinetic (PK) profile in UC patients by intensive sampling via DBS.
Methods: First, DBS were obtained through spotting of 45 μL of golimumab (0.2–20 μg/mL) or anti-golimumab antibody (20–200 ng/mL) spiked in whole citrated blood, to a filter paper. After punching, DBS were extracted and DBS extracts were analysed on both the MA-GOM171D8/MA-GOM159B8-HRP ELISA and the MA-GOM159B8 bridging ELISA. Extraction efficacy, accuracy, imprecision, sensitivity and robustness were determined as well as the impact of anti-golimumab antibodies on the detection of golimumab (and vice versa). Second, DBS were obtained by spotting blood obtained through a finger prick of eight golimumab-treated patients with UC of whom serum was taken simultaneously by venepuncture, allowing the calculation of a real-life conversion factor between golimumab serum concentration and DBS extract.
Results: The selected extraction condition yielded an average extraction efficiency of 54% and 53% for golimumab and anti-golimumab determination, respectively. Overall-assay accuracy and imprecision were between 80–120% and <15%, respectively, for each concentration analysed. Storing the sampling papers at room temperature for one month or the extracts at −20°C for three months did not impair DBS recovery. The presence of golimumab hampered the detection of anti-golimumab and vice versa. A real-life conversion factor of 3.8±0.3 (n=6) from DBS to serum was calculated. The blood volume per spot did not influence the results if it had at least a diameter of six mm, which was not the case in two out of eight patients and is the main drawback of this method.
Conclusions: The described DBS method is robust and can be used as a patient friendly and inexpensive method to perform rich sampling in patients treated with biologic agents. Proper patient education on how to sample is essential and will result in an accurate determination of exposure to golimumab in patients with UC. The method will be applied in a prospective cohort of ten patients with UC by collecting 20–40 DBS per patient over time.