TY  - JOUR
A1  - Eyerich, Kilian
A1  - Weisenseel, Peter
A1  - Pinter, Andreas
A1  - Schäkel, Knut
A1  - Asadullah, Khusru
A1  - Wegner, Sven
A1  - Muñoz-Elias, Ernesto J.
A1  - Bartz, Holger
A1  - Taut, Friedmann J. H.
A1  - Reich, Kristian
T1  - 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)
T2  - BMJ open
N2  - 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3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks.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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63018
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-630182
SN  - 2044-6055
N1  - 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.
VL  - 11
IS  - 9, art. e049822
SP  - 1
EP  - 10
PB  - BMJ Publishing Group
CY  - London
ER  -