Guselkumab (GUS) is a human therapeutic antibody targeting IL-23, a key driver of pathogenic T cells in chronic plaque psoriasis (PSO).  VOYAGE 2 is a Phase 3 study that evaluated the efficacy of GUS in moderate-to-severe PSO and included a randomized withdrawal experiment. We explored the potential association of serum biomarkers and clinical parameters with response following treatment withdrawal. 
Subjects initially randomized to GUS who achieved ≥90% improvement vs baseline in the PSO Area and Severity Index (PASI 90 response) at WK 28 were re-randomized to either continue GUS (n = 193) or withdraw from GUS (n = 182). Serum biomarkers were evaluated at baseline, WK 28 and then every 4 WK through WK 48. Clinical parameters evaluated included disease duration, body mass index (BMI), baseline body surface area and PASI score, WK 28 PASI score, and GUS pharmacokinetic parameters. 
PASI 90 response was better maintained at WK 48 in the continuous maintenance group compared to the withdrawal group (p < 0.001). However, sustained efficacy through 28 weeks after the last dose of GUS was observed in a proportion of patients (36.8%). Maintenance of PASI 90 response after drug withdrawal was associated with continued suppression of serum IL-17A, IL-17F and IL-22, while loss of response (<PASI75) was associated with increased serum levels of these cytokines (P≤0.05 IL-17F WK 40, 44 and 48, IL-17A WK 44 and 48, and IL-22 WK 48). 
These data support the hypothesis that IL-23 plays a regulatory role in the expansion and maintenance of Th17, Th22 and related T cell subsets that produce IL-17A, IL-17F and IL-22. These observations provide rationale for further exploration of the effect of IL-23 blockade on the fate of pathogenic T cell subsets associated with PSO and sustained response after withdrawal of therapy in some patients.

Sustained Response Following Withdrawal of Guselkumab Treatment Correlates With Reduced Th17 and Th22 Effector Cytokine Levels