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Safety and efficacy of guselkumab in Japanese patients with moderate‐to‐severe plaque psoriasis: a randomized, placebo‐controlled, ascending‐dose study
Author(s) -
Nemoto O.,
Hirose K.,
Shibata S.,
Li K.,
Kubo H.
Publication year - 2018
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.16236
Subject(s) - medicine , psoriasis area and severity index , placebo , adverse effect , discontinuation , psoriasis , body surface area , randomized controlled trial , pharmacokinetics , gastroenterology , randomization , placebo controlled study , surgery , dermatology , double blind , pathology , alternative medicine
Summary Background The interleukin ( IL )‐23/ IL ‐17 pathway is central in the pathogenesis of psoriasis. The favourable efficacy and safety of guselkumab, an IL ‐23‐specific monoclonal antibody, has been demonstrated in global phase III studies of plaque psoriasis. Objectives To evaluate the safety, efficacy and pharmacokinetics of single‐dose subcutaneous guselkumab in Japanese patients with moderate‐to‐severe plaque psoriasis. Methods Patients with ≥ 10% of total body surface area involvement and a Psoriasis Area and Severity Index ( PASI ) ≥ 12 were randomized (5 : 1) to receive guselkumab or placebo in four cohorts of this double‐blind, placebo‐controlled, single ascending‐dose, single‐centre study. Safety, pharmacokinetics and clinical response were monitored at baseline and specific time points over a 24‐week follow‐up period. Results To week 24, 55% (11/20) of patients in the guselkumab group and 50% (2/4) in the placebo group experienced ≥1 adverse event ( AE ). No deaths, serious AE s or AE s leading to treatment discontinuation were reported. Maximum clinical response was seen at week 16 with PASI 75 (≥ 75% improvement from baseline PASI ) response in two of five (10 mg), four of five (30 mg and 300 mg) and three of five (100 mg) patients; and PASI 90 (≥ 90% improvement from baseline PASI ) in zero of five (10 mg), three of five (30 mg), two of five (100 mg) and three of five (300 mg) patients. Mean maximum serum concentration (C max ) and area under the curve from time zero to infinity values increased in a dose‐proportional manner with a mean terminal half‐life of 15·6–17·6 days and median time to reach C max of 4–6 days. Conclusions Guselkumab was generally well‐tolerated and exhibited sustained high levels of clinical response in Japanese patients with moderate‐to‐severe psoriasis.