{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:43:44Z","timestamp":1790775824017,"version":"4.1.0"},"reference-count":65,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"unspecified","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Janssen, France","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Janssen-Cilag GmbH, Germany","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,8,3]]},"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>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 (\u22642 years) or longer (&gt;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 (\u2018super-responders\u2019 (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 &lt;3 at week 68. Participants with PASI &lt;3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks.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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Approval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      Registered at ClinicalTrials.gov (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT03818035\">NCT03818035<\/jats:ext-link>\n                      ). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-049822","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T11:38:41Z","timestamp":1631533121000},"page":"e049822","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"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)"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct03818035","registry":"10.18810\/clinical-trials-gov","type":"preResults"},{"clinical-trial-number":"nct03818035","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Kilian","family":"Eyerich","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Dermatology and Venereology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Weisenseel","sequence":"additional","affiliation":[{"name":"Dermatologikum Hamburg GmbH, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Pinter","sequence":"additional","affiliation":[{"name":"University Hospital Frankfurt am Main, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Sch\u00e4kel","sequence":"additional","affiliation":[{"name":"Department of Dermatology, and Interdisciplinary Center for Chronic Inflammatory Diseases, University Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khusru","family":"Asadullah","sequence":"additional","affiliation":[{"name":"Dermatological Practice, Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Wegner","sequence":"additional","affiliation":[{"name":"Janssen-Cilag GmbH, Neuss, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto J","family":"Mu\u00f1oz-Elias","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Bartz","sequence":"additional","affiliation":[{"name":"Janssen-Cilag, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedmann J H","family":"Taut","sequence":"additional","affiliation":[{"name":"TautScience and Service Ltd, Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-4332","authenticated-orcid":false,"given":"Kristian","family":"Reich","sequence":"additional","affiliation":[{"name":"Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"2025121512074995000_11.9.e049822.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2016.07.064"},{"key":"2025121512074995000_11.9.e049822.2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800013"},{"key":"2025121512074995000_11.9.e049822.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042915-103905"},{"key":"2025121512074995000_11.9.e049822.4","unstructured":"World Health Organization . 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