The association between clinical response to ustekinumab and immunogenicity to ustekinumab and prior adalimumab

Background Immunogenicity due to antidrug antibodies (ADA) to tumor necrosis factor (TNF)-? antagonists is known to decrease treatment response. However, few studies have investigated ADA in ustekinumab, an interleukin-12 and -23 antagonist, in a clinical setting. This study aimed to investigate the immunogenicity of ustekinumab and its clinical consequences in psoriasis. Methods This prospective observational study enrolled 76 patients with plaque psoriasis who were treated with ustekinumab for a minimum of 7 months. Blood samples were drawn just prior to scheduled ustekinumab injection during clinic visits. Levels of anti-ustekinumab antibody (AUA) and serum ustekinumab concentration were measured respectively by radioimmunoassays and enzyme-linked immunoassays respectively, and correlated to clinical data and Psoriasis Area and Severity Index (PASI). Results AUA was detected in 6.5% of patients after a mean of 13 months of treatment. Patients with positive AUA had significantly lower serum ustekinumab concentrations (0.01 vs. 0.2 mg/L, p<0.001) and lower PASI 50 response than patients without AUA (0% vs. 69%, p = 0.004). The percentage of AUA formation was comparable between patients who had failed previous adalimumab with or without anti-adalimumab antibodies (AAA) (14.3% vs. 12.5%, p = 1.00). However, a higher proportion of switchers without AAA obtaining PASI50 (71.4% vs. 37.5%) and PASI75 response (42.9% vs.12.5%) within 7 months of ustekinumab treatment than with AAA though this difference did not reach statistical significance. Conclusions Our results suggest that presence of AUA was significantly associated with treatment failure for ustekinumab, though limited by a small sample size. Also, determining the presence of ADA to antecedent TNF-α antagonists may assist in choosing an optimized subsequent treatment modality achieving treatment success. ? 2015 Chiu et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.