317 Anti-drug antibody formation against biological agents in psoriasis

Abstract

Biological agents are used in psoriasis with great efficacy but antidrug antibody(ADA)formation may occur and stand behind the lack of clinical efficacy. These can be neutralizing or non-neutralizing antibodies-may bind to the active cytokine binding place, can change the pharmacokinetics, can form immunocomplexes with biologicals. In our cross-sectional study we measured ADA formation and drug concentration in samples of 160 patients. Bridging ELISA was used to evaluate ADA-s in sera, the serum drug concentration at the time of sample collection, PASI (Psoriasis Area and Severity Index)was calculated and drug switch(when PASI50 answer lost) was registered. In case of adalimumab (n=65) 18.4% of patients had ADA formation, the serum drug concentration was significantly higher in ADA-s (p=0.001). In patients on infliximab (n=49) 33% had ADA, the serum drug concentration was significantly higher in ADA-s (p<0.05). We can not identify any ADA in patients on etanercept (n=46), 83% had measurable drug concentration. The loss of efficacy and therapy switch was39%in ADA+patients and 15%(n=20) in ADA-s, (p=0,003). Among patients on infliximab loss of efficacy and a need for drug switch was required in 50% of ADA+ patients, and in 18% of ADA- patients. In case of adalimumab 25% of ADA+ patients lost efficacy and switched the therapy, it was 7,5% of ADA- subjects. There was no detectable ADA formation under etanercept while there was therapy switch in 22%. In the background of lost efficacy after a good therapeutical response we should properly search for ADA formation beside other causative factors. In case of adalimumab and infliximab there was a significant correlation between ADA formation, serum drug concentration, loss of PASI50 answer and consequential therapy switch. Monitorizing ADA formation and serum drug concentration can be a great tool for optimizing therapy and maintaining cost-effectivity.