PracticeUpdate Conference Series: IID 2018

Response to IL-23 Blockade With Guselkumab Associated With HLA-Cw6 Status in Patients With Psoriasis

A distinct, but modest, positive association has been identified between response to interleukin (IL) 23 blockade using guselkumab and HLA-Cw6-positive status among patients with psoriasis, reports a post hoc subanalysis of data from the phase III VOYAGE 1 and 2 trials. X uejun Liu, PhD, of Janssen Research & Development, LLC in San Diego, California, explained that modestly better responses to Both trials assessed responses at week 16 vs pla- cebo for the two coprimary endpoints:

ƒ ƒ The proportion of subjects who achieved an investigator’s global assessment score of 0 (cleared) or 1 (minimal) ƒ ƒ The proportion of subjects who achieved at least a 90% reduction from baseline in Psoriasis Area and Severity Index (PASI 90) composite score Comparisons between guselkumab and adali- mumab were secondary endpoints at the following time points: ƒ ƒ Week 16 (VOYAGE 1 and VOYAGE 2), the propor- tions of subjects who achieved an investigator’s global assessment score of 0 or 1, PASI 90, and PASI 75 response ƒ ƒ Week 24 (VOYAGE 1 and VOYAGE 2) ƒ ƒ Week 48 (VOYAGE 1), the proportions of subjects who achieved an investigator’s global assess- ment score of 0, 0 or 1, and a PASI 90 response Other evaluated outcomes included improvement in psoriasis symptoms assessed on the Psoriasis Symptoms and Signs Diary and improvements in psoriasis of the scalp at week 16. In both trials, subjects were predominantly men and white, mean age 44 years, and mean weight of 90 kg.

ustekinumab, a fully human monoclonal antibody that targets the common p40 subunit of IL-12 and -23, have been reported among patients with pso- riasis who carried the human leukocyte antigen (HLA) Cw6 (C*06.01) allele. Guselkumab is a fully human monoclonal antibody that binds the p19 subunit of IL-23 and blocks IL-23-mediated signaling. IL-23 is a naturally occurring cytokine involved in normal inflamma- tory and immune responses. Guselkumab inhibits the release of proinflammatory cytokines and chemokines. Dr. Liu and colleagues set out to determine whether better responses to guselkumab would be similarly observed among patients carrying the HLA-Cw6 allele in large cohorts of patients from the phase III VOYAGE 1 and 2 trials that evaluated guselkumab in patients with moderate to severe plaque psoriasis. In VOYAGE 1 and 2, 1443 subjects were randomized to either guselkumab (100 mg at weeks 0 and 4 and every 8 weeks thereafter); placebo; or adal- imumab (80 mg at week 0 and 40 mg at week 1, followed by 40 mg every other week thereafter).

Dr. Xuejun Liu

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