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 rat...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
September 13, 2021
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| In: |
BMJ open
Year: 2021, Volume: 11, Issue: 9, Pages: 1-10 |
| ISSN: | 2044-6055 |
| DOI: | 10.1136/bmjopen-2021-049822 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/bmjopen-2021-049822 Verlag, lizenzpflichtig, Volltext: https://bmjopen.bmj.com/content/11/9/e049822 
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| Author Notes: | Kilian Eyerich, Peter Weisenseel, Andreas Pinter, Knut Schäkel, Khusru Asadullah, Sven Wegner, Ernesto J. Muñoz-Elias, Holger Bartz, Friedmann J.H. Taut, Kristian Reich |
| Summary: | 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3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks.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. |
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| Item Description: | Gesehen am 11.11.2021 |
| Physical Description: | Online Resource |
| ISSN: | 2044-6055 |
| DOI: | 10.1136/bmjopen-2021-049822 |