IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE)
- Background: Guselkumab 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 analysis Here 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3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks.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 dissemination: Approval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki. Trial registration number: Registered 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.
Author: | Kilian EyerichORCiDGND, Peter WeisenseelGND, Andreas PinterORCiDGND, Knut SchäkelGND, Khusru Asadullah, Sven Wegner, Ernesto J. Muñoz-Elias, Holger Bartz, Friedmann J. H. Taut, Kristian ReichORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-630182 |
DOI: | https://doi.org/10.1136/bmjopen-2021-049822 |
ISSN: | 2044-6055 |
Parent Title (English): | BMJ open |
Publisher: | BMJ Publishing Group |
Place of publication: | London |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/09/13 |
Date of first Publication: | 2021/09/13 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2022/03/03 |
Volume: | 11 |
Issue: | 9, art. e049822 |
Page Number: | 10 |
First Page: | 1 |
Last Page: | 10 |
Note: | The GUIDE study is funded by Janssen-Cilag, Germany and Janssen, France. Editorial support was provided by Cello Health MedErgy and funded by Janssen-Cilag, Germany and Janssen, France. |
HeBIS-PPN: | 491730330 |
Institutes: | Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (English): | Creative Commons - Namensnennung-Nicht kommerziell 4.0 |