Immunogenicity and pharmacokinetics of guselkumab among patients with moderate‐to‐severe psoriasis in VOYAGE‐1 and VOYAGE‐2

Immunogenicity and pharmacokinetics of guselkumab among patients with moderate-to-severe psoriasis in VOYAGE-1 and VOYAGE-2Dear Editor, Development of anti-drug antibodies (ADA) to biologic agents may impact the effectiveness and/or safety of psoriasis treatment. [1][2]2][3] As several factors can influence development (e.g.molecular structure, dosing regimen) or clinical impact (e.g.neutralising antibodies [NAb]) of ADA, 4-8 the ability to predict the immunogenicity of any particular biologic is limited.Thus, evaluating the clinical significance of ADA over time is informative.Here, 5-year data from two large Phase 3, randomized studies (VOYAGE-1 and VOYAGE-2) were assessed for long-term presence and clinical impact of ADA to guselkumab, a fully human IgG1 monoclonal antibody that binds the p19 subunit of interleukin-23.In VOYAGE-1 and VOYAGE-2, guselkumab demonstrated superior efficacy to placebo and adalimumab with a favourable safety profile in adults with moderate-to-severe plaque psoriasis. 9,10In both studies, patients randomized to placebo or adalimumab switched to guselkumab by Week (W)76, at the latest, and continued receiving guselkumab through W252.Overall, 774/837 patients in VOYAGE-1 and 947/992 in VOYAGE-2 received guselkumab.Guselkumab ADA were detected using a validated, drug-tolerant electrochemiluminescence immunoassay (ECLIA) method (Meso Scale Discovery).Among guselkumab-treated patients with evaluable ADA samples, 111/770 (14.4%) and 146/943 (15.5%) patients in VOYAGE-1 and VOYAGE-2, respectively, were ADA-positive at some point through W264; 82.0% had peak titres 1:160.In VOYAGE-1, among guselkumab-treated patients with evaluable ADA samples, 16.1% of patients who continued guselkumab through W252 were ADA-positive versus 7.4% of those who discontinued/withdrew before W252; corresponding values for VOYAGE-2 were 15.8% and 14.4%.Higher ADA titres were not observed among patients who discontinued guselkumab.Only 5 (4.5%) and 8 (5.5%) ADA-positive patients in VOYAGE-1 and VOYAGE-2, respectively, had NAb to guselkumab (defined as 22.46% inhibition of ECLIA signal versus controls), equivalent to 0.76% of guselkumab-treated patients with ADA-evaluable samples across studies.Through W264, serum guselkumab concentrations were comparable between ADA-positive and ADA-negative