Anti-drug Antibody Monitoring of TNF-α Blockers in RA

Therapeutic monitoring of drug trough levels (DLs) may be a cost-effective way to assess the efficacy of tumor necrosis factor (TNF)-α blockers in patients with rheumatoid arthritis (RA), according to a study published in the journal Biologics. 

Therapeutic drug monitoring of TNF blockers is not routine in most clinical practices.  However, obtaining DLs may help guide clinicians in situations when current regimens appear to lose clinical effectiveness. To examine the costs and benefits associated with monitoring TNF blocker DLs, Kari Puolakka, MD, Helsinki University Central Hospital, Helsinki, and colleagues analyzed a clinical database and sample registry from Finland. 

“Monitoring of anti-drug antibodies (ADAbs) or serum concentrations of [biologic disease-modifying antirheumatic drugs for the treatment] of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication,” the authors hypothesized.

Researchers collected infliximab and adalimumab DLs and ADab concentrations from a clinical database of patients with RA. Enzyme-linked immunosorbent assays were used to determine DLs, while radioimmunoassay techniques were use to quantify ADAbs.

Cut-off points to define “optimal target levels” were defined by researchers as  ≥2 μg/mL for infliximab and  ≥5 μg/mL for adalimumab.  ADab positivity for both infliximab and adalimumab was defined as ≥12 U/mL.  These values were subsequently used in a Markov model to determine optimal treatment strategies for the following 6 months. 

“Transition probabilities related to the nonoptimal treatment response (nonresponse) in the absence of knowledge of DL and ADAb values were derived from previous literature for both the first-line treatment (European League Against Rheumatism response at 6 and 12 months) and the second-line treatment”, the authors wrote. 

The economic impact of clinical decision-making was then modeled for 100 hypothetical patients over a 3-6 month period. 

Target DLs were measured in 42% of samples taken from patients treated with adalimumab, and in 50.4% of samples taken from patients treated with infliximab.ADAb positivity was found in 20% of adalimumab-treated patient samples, and in 13.5% of infliximab-treated patient samples. ADAbs were found in 52.3% and 41.3% of samples with low adalimumab or infliximab DLs, respectively. 

After running the economic impact model, combined measurements of DLs and ADAbs were cost-saving when compared with non-testing when the therapeutic drug monitoring results affected the treatment decision in 2-5 of 100 patients.

Summary and Clinical Applicability

“This study indicates that routine monitoring of drug level and ADAbs is cost-beneficial in clinical practice, thereby improving the decision-making process in using TNF-α blockers”, the authors concluded.

Limitations and Disclosures

This study was potentially limited by use of cut-off points to define treatment response and by the possibility of ADAb positivity testing variability.  These results also incorporated cost estimations based on hypothetical models. Approximations of cost savings would need to be adjusted for other countries and health insurance systems.

A large prospective study evaluating costs associated with monitoring, medication, and clinical follow-up could validate these findings. 

Several study co-authors report financial relationships with the following pharmaceutical companies: Abbvie, BMS, MSD, Pfizer, Roche, and UCB. 

Reference

Laine J, Jokiranta TS, Eklund KK, Väkeväinen M, Puolakka K. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers. Biologics. 2016;10:67-73.