First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis

Zhuang, Yanli; Calderón, César; Marciniak, Stanley J.; Bouman‐Thio, Esther; Szapary, Philippe; Yang, Tong‐Yuan; Schantz, Allen; Davis, Hugh M.; Zhou, Honghui; Xu, Zhenhua

doi:10.1007/s00228-016-2110-5

Cited by 78 publications

(65 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The safety, efficacy and pharmacokinetic profile of guselkumab observed in this phase I study is consistent with that reported in the global phase I guselkumab psoriasis study . Further, the efficacy and safety up to 1 year in over 2000 patients in a phase II and two phase III studies of guselkumab in a moderate‐to‐severe psoriasis population have been reported .…”

Section: Discussionsupporting

confidence: 88%

“…). Dose selection was based on a previously conducted non‐Japanese phase I study . Dose escalation to sequential cohorts was guided by safety and tolerability data from previous dose cohorts.…”

Section: Methodsmentioning

confidence: 99%

“…Dose selection was based on a previously conducted non-Japanese phase I study. 15 Dose escalation to sequential cohorts was guided by safety and tolerability data from previous dose cohorts. Central randomization was implemented in this study based on a computer-generated randomization schedule.…”

Section: Methodsmentioning

confidence: 99%

“…[11][12][13][14] Guselkumab, a human monoclonal antibody that specifically targets the p19 subunit of IL-23, antagonizes the IL-23/T helper (Th)17 axis and causes a reduction in the inflammatory cascade associated with psoriasis. 6 A comprehensive global development programme, including phase I-III studies, 7,8,15 has characterized the favourable efficacy and safety profile of guselkumab in addition to the pharmacokinetic parameters. Although psoriasis is known to more frequently affect Western populations, the prevalence in Asian patients is increasing.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Safety and efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: a randomized, placebo-controlled, ascending-dose study

Nemoto

Hirose²,

Shibata³

et al. 2018

Br J Dermatol

View full text Add to dashboard Cite

SummaryBackground 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 AEs or AEs 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 15Á6-17Á6 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.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Safety and efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: a randomized, placebo-controlled, ascending-dose study

Nemoto

Hirose²,

Shibata³

et al. 2018

Br J Dermatol

View full text Add to dashboard Cite

show abstract

“…Complete clearing is becoming a realistic expectation; 56·3% of patients treated with risankizumab sustained a PASI100 response at week 52 . The half‐life of tildrakizumab and risankizumab is 20–28 days; guselkumab's half‐life is 12–19 days . The far longer duration of pharmacological action supports a fundamental role for IL‐23 in psoriasis pathogenesis.…”

mentioning

confidence: 99%

The perceived promise of p19 inhibitors

Cline

Feldman

2018

Br J Dermatol

View full text Add to dashboard Cite

show abstract

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Sbidian

Chaimani

García‐Doval

et al. 2017

Cochrane Database of Systematic Reviews

266

309

View full text Add to dashboard Cite

Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.

show abstract

First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis

Abstract: Guselkumab pharmacokinetic profiles were generally comparable between healthy subjects and patients with psoriasis. Guselkumab, administered as an IV infusion or SC injection, was well tolerated in healthy subjects and patients with psoriasis.

Cited by 78 publications

References 18 publications

Safety and efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: a randomized, placebo-controlled, ascending-dose study

Safety and efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: a randomized, placebo-controlled, ascending-dose study

The perceived promise of p19 inhibitors

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Contact Info

Product

Resources

About