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Evaluating guselkumab: an anti-IL-23 antibody for the treatment of plaque psoriasis.

ABSTRACT: The approval of guselkumab marks the entry of the IL-23 inhibitor class into the therapeutic armamentarium for patients with moderate-to-severe plaque psoriasis. This class specifically targets the upstream portion of the type 17 helper T (Th17) axis, which has been implicated as a key driver of the abnormal inflammatory state observed in psoriasis. Guselkumab is highly efficacious, with over 85% of the patients achieving ?75% reduction in Psoriasis Area and Severity Index from baseline (PASI 75) and over 70% of the patients achieving PASI 90 response in its Phase III clinical trials. Additionally, this medication is well-tolerated, with non-serious infections such as nasopharyngitis and upper respiratory infections (URIs) being the most common adverse events (AEs) reported in its clinical trials. Guselkumab offers yet another effective treatment option in the rapidly growing list of available biological therapies for moderate-to-severe plaque psoriasis.

SUBMITTER: Yang EJ

PROVIDER: S-EPMC6587972 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Evaluating guselkumab: an anti-IL-23 antibody for the treatment of plaque psoriasis.

Yang Eric J EJ Smith Mary Patricia MP Ly Karen K Bhutani Tina T

Drug design, development and therapy 20190618

The approval of guselkumab marks the entry of the IL-23 inhibitor class into the therapeutic armamentarium for patients with moderate-to-severe plaque psoriasis. This class specifically targets the upstream portion of the type 17 helper T (Th17) axis, which has been implicated as a key driver of the abnormal inflammatory state observed in psoriasis. Guselkumab is highly efficacious, with over 85% of the patients achieving ≥75% reduction in Psoriasis Area and Severity Index from baseline (PASI 75 ...[more]

PMID: 31354244

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Project description:BackgroundThe role of interleukin-12 (IL-12), interleukin-23 (IL-23), and interleukin-17 (IL-17) has been recognized in psoriasis pathogenesis, and new drugs targeting this axis have already been developed which may provide a new therapeutic approach for patients with moderate to severe psoriasis.ObjectiveTo compare the direct and indirect evidences of the efficacy and safety of brodalumab, secukinumab, ixekizumab, ustekinumab, guselkumab, tildrakizumab, and risankizumab in the short-term treatment of moderate to severe plaque psoriasis using network meta-analysis (NMA).MethodsA comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for the available relevant studies. NMA was conducted by Stata 15.0 software using relative risks (RR) with 95% confidence interval to assess the clinical effectiveness and safety. Ranked the efficacy and safety for each drug accordance with the surface under the cumulative ranking curve (SUCRA).ResultsThis meta-analysis included 28 studies. All the interventions performed better than placebo in short-term achievement. Based on the result of SUCRA, ixekizumab 80 mg every 2 weeks ranked the highest in short-term achievement of PASI 75 (SUCRA = 93.0%). Brodalumab 210 mg ranked the highest in short-term achievement of PASI 100 (SUCRA = 85.0%). Secukinumab 300 mg ranked the highest in short-term achievement of sPGA 0/1 or IGA 0/1 or PGA 0/1 (SUCRA = 98.1%). In terms of having a risk of adverse events, the rates were higher in brodalumab, secukinumab, ixekizumab, and ustekinumab 45 mg compared with placebo. Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of adverse events during short-term treatment (SUCRA = 4.5%). Guselkumab 50 mg ranked the highest in the risk of serious adverse events during short-term treatment (SUCRA = 25.9%). Ixekizumab 80 mg every 4 weeks ranked the highest in the risk of discontinuations due to adverse events during short-ter treatment (SUCRA = 10.7%).ConclusionsIL-17, IL-12/23, and IL-23 inhibitors had high efficacy in the achievement of PASI 75, PASI 100, and sPGA 0/1 or IGA 0/1 or PGA 0/1 in moderate to severe plaque psoriasis after 12 or 16 weeks of treatment. IL-17 inhibitors showed superior efficacy. However, its clinical safety was poor. Risankizumab appeared to have relatively high efficacy and low risk. The clinical tolerance of other biological agents needs to be further observed.

Project description:BackgroundGuselkumab is an interleukin (IL)-23 pathway blocker with proven efficacy in patients with moderate-to-severe plaque psoriasis. Early intervention with guselkumab may result in changes to the clinical disease course versus later intervention.Methods and analysisHere we present the rationale and design of a phase 3b, randomised, double-blind, multicentre study (GUIDE), comparing treatment effects of guselkumab in patients with short (≤2 years) or longer (>2 years) duration of plaque-type psoriasis, measured from first appearance of psoriatic plaques. Participants achieving skin clearance (Psoriasis Area and Severity Index (PASI)=0) by week 20 and maintaining complete clearance at week 28 visit ('super-responders' (SRe)) will be randomised to continue approved maintenance dosing every 8 weeks (q8w) versus an investigational maintenance dosing interval of 16 weeks (q16w) until week 68. Primary endpoint: proportion of participants in the q8w vs q16w arms with absolute PASI <3 at week 68. Participants with PASI <3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks. Participants not achieving SRe criteria (non-SRe) will remain in the study with q8w guselkumab dosing through week 68. Additional to serum samples obtained from all patients, skin biopsies and whole-blood samples will be taken from SRe and non-SRe participants at various time points in optional substudies. Analyses include: genetics; immunophenotyping (fluorescence-activated cell sorting); gene and protein expression profiling; immunohistology. By merging clinical endpoints with mechanistic findings, this study aims to elucidate how IL-23 blockade with guselkumab can modify the disease course by altering molecular and cellular drivers that cause relapse after treatment withdrawal, particularly among SRe.Ethics and disseminationApproval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki.Trial registration numberRegistered at ClinicalTrials.gov (NCT03818035). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.

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Evaluating guselkumab: an anti-IL-23 antibody for the treatment of plaque psoriasis.

Publications

Evaluating guselkumab: an anti-IL-23 antibody for the treatment of plaque psoriasis.

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