IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis

• Verfasst von: Eyerich, Kilian [VerfasserIn]
• Verfasst von: Weisenseel, Peter [VerfasserIn]
• Verfasst von: Pinter, Andreas [VerfasserIn]
• Verfasst von: Schäkel, Knut [VerfasserIn]
• Verfasst von: Asadullah, Khusru [VerfasserIn]
• Verfasst von: Wegner, Sven [VerfasserIn]
• Verfasst von: Muñoz-Elias, Ernesto J. [VerfasserIn]
• Verfasst von: Bartz, Holger [VerfasserIn]
• Verfasst von: Taut, Friedmann J. H. [VerfasserIn]
• Verfasst von: Reich, Kristian [VerfasserIn]
• Titel: IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis
• Titelzusatz: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE)
• Verf.angabe: Kilian Eyerich, Peter Weisenseel, Andreas Pinter, Knut Schäkel, Khusru Asadullah, Sven Wegner, Ernesto J. Muñoz-Elias, Holger Bartz, Friedmann J.H. Taut, Kristian Reich
• E-Jahr: 2021
• Jahr: September 13, 2021
• Umfang: 10 S.
• Fussnoten: Gesehen am 11.11.2021
• Titel Quelle: Enthalten in: BMJ open
• Ort Quelle: London : BMJ Publishing Group, 2011
• Jahr Quelle: 2021
• Band/Heft Quelle: 11(2021), 9, Artikel-ID e049822, Seite 1-10
• ISSN Quelle: 2044-6055
• DOI: doi:10.1136/bmjopen-2021-049822
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: adult dermatology
• Sach-SW: protocols & guidelines
• Sach-SW: psoriasis
• K10plus-PPN: 1777282381

Abstract

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.