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 ration...
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BMJ Publishing Group
2021-09-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/11/9/e049822.full |
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| author | Kristian Reich Kilian Eyerich Knut Schäkel Peter Weisenseel Andreas Pinter Khusru Asadullah Sven Wegner Ernesto J Muñoz-Elias Holger Bartz Friedmann J H Taut |
| author_facet | Kristian Reich Kilian Eyerich Knut Schäkel Peter Weisenseel Andreas Pinter Khusru Asadullah Sven Wegner Ernesto J Muñoz-Elias Holger Bartz Friedmann J H Taut |
| author_sort | Kristian Reich |
| collection | DOAJ |
| description | 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3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks.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. |
| format | Article |
| id | doaj-art-673be33cf2a54e4aba93d38bcb985891 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2021-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-673be33cf2a54e4aba93d38bcb9858912025-08-20T02:18:32ZengBMJ Publishing GroupBMJ Open2044-60552021-09-0111910.1136/bmjopen-2021-049822IL-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)Kristian Reich0Kilian Eyerich1Knut Schäkel2Peter Weisenseel3Andreas Pinter4Khusru Asadullah5Sven Wegner6Ernesto J Muñoz-Elias7Holger Bartz8Friedmann J H Taut94University Medical Center Hamburg-Eppendorf, Skin Inflammation Center, Hamburg, and Dermatologikum, Berlin, GermanyDepartment of Medicine, Division of Dermatology and Venereology, Karolinska Institute, Stockholm, SwedenDepartment of Dermatology, and Interdisciplinary Center for Chronic Inflammatory Diseases, University Hospital Heidelberg, Heidelberg, GermanyDermatologikum Hamburg GmbH, Hamburg, GermanyHospital of the Goethe University Frankfurt, Frankfurt am Main, GermanyDermatological Practice, Potsdam, GermanyJanssen-Cilag GmbH, Neuss, GermanyJanssen Research & Development, LLC, San Diego, California, USAJanssen-Cilag, Vienna, AustriaTautScience and Service Ltd, Konstanz, GermanyBackground 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.https://bmjopen.bmj.com/content/11/9/e049822.full |
| spellingShingle | Kristian Reich Kilian Eyerich Knut Schäkel Peter Weisenseel Andreas Pinter Khusru Asadullah Sven Wegner Ernesto J Muñoz-Elias Holger Bartz Friedmann J H Taut 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) BMJ Open |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/11/9/e049822.full |
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