Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Sep 1;160(9):953-963.
doi: 10.1001/jamadermatol.2024.2463.

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial

Kilian Eyerich  1 , Khusru Asadullah  2   3 , Andreas Pinter  4 , Peter Weisenseel  5 , Kristian Reich  6 , Carle Paul  7 , Robert Sabat  8 , Kerstin Wolk  8 , Stefanie Eyerich  9 , Felix Lauffer  9 , Julianty Angsana  10 , Friedemann J H Taut  11 , Kristen Kohler  10 , Yanqing Chen  10 , Jocelyn Sendecki  10 , Monica W L Leung  10 , Sven Wegner  12 , Yvonne Personke  12 , Mario Gomez  13 , Nenja Krüger  12 , Sarah Tabori  12 , Knut Schäkel  14
Affiliations
Clinical Trial

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial

Kilian Eyerich et al. JAMA Dermatol. .

Erratum in

  • Errors in Figures 1 and 3.
    [No authors listed] [No authors listed] JAMA Dermatol. 2024 Nov 1;160(11):1257. doi: 10.1001/jamadermatol.2024.4370. JAMA Dermatol. 2024. PMID: 39382861 Free PMC article. No abstract available.

Abstract

Importance: Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies.

Objective: To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis.

Design, setting, and participants: The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis. In study part 2, reported herein, first and last patient visits were September 2019 and March 2022, respectively.

Interventions: In GUIDE part 1 (week [W]0-W28), patients received guselkumab, 100 mg, at W0, W4, W12, and W20. Those achieving a Psoriasis Area and Severity Index (PASI) of 0 at both W20 and W28 were termed super responders (SRes). In part 2 (W28-W68), SRes were randomized to guselkumab, 100 mg, every 8 weeks or every 16 weeks; non-SRes continued open-label guselkumab every 8 weeks.

Main outcomes and measures: Primary objective was to demonstrate noninferiority (with a 10% margin) of guselkumab every 16 weeks vs every 8 weeks dosing among SRes for maintenance of disease control (PASI <3 at W68). Biomarker substudies assessed immunologic effects in skin and blood.

Results: Overall, 822 patients received guselkumab in part 2 (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). Among SRes, mean (SD) age was 39.4 (14.1) years, 95 (32.0%) were female, and 202 (68.0%) were male. The primary end point of noninferiority for guselkumab every 16 weeks vs every 8 weeks in SRes was met (P = .001), with 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes receiving every 16 weeks and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes receiving dosing every 8 weeks having PASI lower than 3 at W68. Clinical effects corresponded with immunologic changes; skin CD8-positive tissue-resident memory T (TRM)-cell count decreased quickly from baseline, remaining low in both dosing groups. Similarly, serum IL-17A, IL-17F, IL-22, and β defensin (BD)-2 levels decreased significantly from baseline, remaining low in both dosing groups to W68. Guselkumab was well-tolerated; no new safety signals were identified.

Conclusions and relevance: Psoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation. We present the first randomized trial providing evidence that, in patients with early complete skin clearance at 2 consecutive visits (W20 and W28), extending the guselkumab dosing interval may control disease activity.

Trial registration: ClinicalTrials.gov Identifier: NCT03818035.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Prof K. Eyerich reported personal fees from Janssen during the conduct of the study; personal fees from AbbVie, Almirall, Boehringer Ingelheim, LEO Pharma, Lilly, Novartis, and Sanofi outside the submitted work. Prof Asadullah reported personal fees from Janssen during the conduct of the study; personal fees from AbbVie, Celltrion, Bristol-Myers Squibb, Galderma, La Roche-Posay, LEO Pharma, L’Oréal, Novartis, Parexel International, Pierre Fabre, Roxall, Sanofi Genzyme, TFS Trial Form Support, UCB, ICON, and Janssen outside the submitted work. Dr Weisenseel reported honoraria for speaker services and advisory boards from Janssen, employer-received honoraria for clinical trials with Janssen during the conduct of the study. Prof Reich reported personal fees from AbbVie, grants from Almirall, Amgen, Boehringer Ingelheim, personal fees from Forward Pharma, Gilead, Galderma, Janssen-Cilag, and Kyowa Kirin, personal fees from LEO Pharma, grants from LEO Pharma, Lilly, personal fees from Lilly, grants from Medac, grants from Novartis, personal fees from Ocean Pharma, grants from Cesra, grants from Pfizer, personal fees from Sanofi, and grants from UCB outside the submitted work; in addition, Prof Reich is cofounder of MoonLake Immunotherapeutics. Prof Paul reported grants from Janssen during the conduct of the study; personal fees from AbbVie, Bristol-Myres Squibb, Boehringer Ingelheim, Lilly, Iqvia, Janssen, Mylan, Pfizer, Pierre Fabre, Sanofi, and UCB outside the submitted work. Prof Sabat reported payment to institution from Janssen-Cilag GmbH (Charité–Universitätsmedizin Berlin) during the conduct of the study; contract with and payment to institution from AbbVie Deutschland GmbH & Co. KG, Boehringer Ingelheim Pharma GmbH & Co. KG, Celgene/Amgen, Celgene/Bristol Myers Squibb, Charité Research Organisation GmbH, CSL Behring GmbH, ICON plc, IQVIA RDS GmbH, Incyte Corporation, MoonLake Immunotherapeutics AG, Novartis Pharma GmbH, Parexel International GmbH, Sanofi–Aventis Deutschland GmbH, TFS Trial Form Support, UCB Biopharma SPRL, and Janssen Research & Development, LLC outside the submitted work; and Prof Sabat had received scientific awards or honoraria for consulting, participation in advisory boards or as speaker for 1 or more of the following: AbbVie Deutschland GmbH & Co. KG, Almirall Hermal GmbH, Amgen GmbH, Bayer Schering Pharma AG, Bruno Bloch Stiftung, Janssen-Cilag GmbH, Novartis Pharma GmbH, UCB Biopharma SPRL, Universitätsmedizin Greifswald, Wundnetz Berlin-Brandenburg e. V. Dr Wolk reported expense allowance for laboratory work from Janssen-Cilag GmbH during the conduct of the study; study expense allowance, payed to institution from Celgene/Amgen, Celgene/Bristol Myers Squibb, Charité Research Organization GmbH, Flexopharm GmbH & Co. KG, and Janssen-Cilag GmbH, grants to institution from Novartis Pharma GmbH, Sanofi–Aventis Deutschland GmbH, and TFS Trial Form Support GmbH outside the submitted work; and Consulting fees/fees for advisory board participaton from Janssen-Cilag, consulting fees/fees for advisory board participaton from Novartis Pharma GmbH, payment for lectures from Novartis Pharma GmbH, Sanofi–Aventis Deutschland GmbH, University Hospital Magdeburg, reimbursement of travel expenses and congress fees in connection with lecture invitation on EHSF congress from the European HS foundation (EHSF,nonfinantial relationship (founder and head, no payment) to the Task force Acne inversa at Arbeitsgemeinschaft Dermatologische Forschung/Consortium for Dermatological Research (Germany). Prof S. Eyerich reported grants from Janssen-Cilag during the conduct of the study; personal fees from Almirall outside the submitted work. Dr Lauffer reported personal fees from Janssen-Cilag and grants from Janssen-Cilag during the conduct of the study; personal fees from Novartis, Eli Lilly, LEO Pharma, AbbVie, and Almirall, grants from Almirall, personal fees from Sanofi, grants from Sanofi, grants from Brystol-Myers Squibb, personal fees from Brystol-Myers Squibb, Amgen, UCB, Hexal, and Janssen-Cilag outside the submitted work. Dr Angsana reported personal fees from Janssen R&D, LLC employment at Janssen R&D, LLC, San Diego, and stockholder of Johnson & Johnson during the conduct of the study; personal fees from Janssen R&D, LLC employment at Janssen R&D, LLC, San Diego, and stockholder of Johnson & Johnson outside the submitted work; in addition, Dr Angsana had a patent for JBI6896USPSP1 pending Janssen. Dr Taut reported personal fees from Janssen-Cilag GmbH during the conduct of the study. Dr Kohler reported personal fees from Janssen R&D, LLC employment at Janssen R&D, LLC, San Diego, during the conduct of the study; personal fees from Janssen R&D, LLC and employment at Janssen R&D, LLC, San Diego outside the submitted work. Dr Chen reported employment Janssen Research and Development of J&J during the conduct of the study; in addition, Dr Chen had a patent for JBI6896USPSP1 pending under Johnson and Johnson. Dr Sendecki reported employment and stockholding from Johnson & Johnson during the conduct of the study. Dr Leung reported personal fees from Johnson & Johnson during the conduct of the study; personal fees from Johnson & Johnson outside the submitted work; in addition, Dr Leung had a patent for provisional pending. Dr Wegner reported to be an employee and shareholder of Janssen. Dr Personke reported employment from Janssen-Cilag during the conduct of the study; and from Janssen-Cilag outside the submitted work. Dr Gomez reported employment from Johnson & Johnson during the conduct of the studyand outside the submitted work. Dr Krüger reported employment at Janssen-Cilag GmbH. Dr Tabori reported employment at Janssen-Cilag GmbH. Prof Schäkel reported study fees from Janssen Cilag, personal fees from Janssen-Cilag, study fees from Bristol-Myers Squibb, Smerud, Lilly, Almirall, Alumis, AbbVie, Sanofi, Galderma, Amgen, Incyte, Pharm-Olam, Moonlake, and Boehringer-Ingelheim, personal fees from Lilly, Bristol-Myers Squibb, Almirall, AbbVie, Sanofi, and Amgen during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) Response Rates at Week 68 (W68) or Over Time Among Super Responders (SRes)
The proportion of patients achieving (A and B) PASI lower than 3 at W68 and over time (primary end point), (C and D) PASI of 1 or lower at W68 and over time, (E and F) PASI of 0 at W68 and over time, (G) mean PASI over time, and (H) DLQI 0/1 response over time, among SRes randomized to guselkumab every 8 weeks vs every 16 weeks dosing (intention-to-treat population). In panels B, D, and F, the percentages at W20 and W28 are less than 100.0 because some patients who had a PASI of 0 had their assessment outside of the predefined visit window; these patients were imputed as nonresponders in this analysis but still considered SRes. Black arrowheads represent open-label guselkumab injections (W0 to W28), gray arrowheads represent blinded guselkumab injections in the every 8 weeks and every 16 weeks groups (W28 to W60), and white arrowheads represent placebo injections. Patients in the every 16 weeks dosing group received placebo injections at W28, W44, and W60. Nonresponder imputation was used for missing data with the exception of mean PASI assessment, for which as-observed data are shown. GUS indicates guselkumab. Panels A to H previously presented at the European Academy of Dermatology & Venereology Congress 2022 and used with permission from Prof Knut Schäkel, MD.
Figure 2.
Figure 2.. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) Response Rates in Non–Super Responders (SRes) Over Time to Week 68 (W68)
The proportion of non-SRe patients achieving (A) PASI lower than 3, PASI of 1 or lower, and PASI of 0, and (B) DLQI lower than 5 and DLQI 0/1 responses from baseline to W68 (intent to treat population). Nonresponder imputation was used for missing data. GUS indicates guselkumab. This Figure was previously presented at the European Academy of Dermatology & Venereology Congress 2022 and used with permission from Prof Knut Schäkel, MD.
Figure 3.
Figure 3.. Interleukin (IL)–17A, IL-17F, IL-22, and β Defensin-2 (BD-2) Serum Levels and Skin CD8-Positive Tissue-Resident Memory (TRM) Cell Count From Baseline to Week 68 (W68)
Mean serum concentration (pg/mL; 95% CI) for (A) IL-17A, (B) IL-17F, and (C) IL-22, and averaged log2 concentration for (D) BD-2, from baseline to W68, among SRes randomized to guselkumab every 8 weeks vs every 16 weeks dosing; (E), CD8-positive TRM cell count (loge, 95% CI) by SRe status. Normalization was defined as a cell count that was not statistically significantly different compared with W0 nonlesional skin. Variation in the number of patients analyzed across visits is the result of patient withdrawals, and (E) the availability of obtaining bead counts. Log cell count represents natural log (cell count of plus 1). BD-2 indicates β defensin-2; GUS, guselkumab; HC, healthy control; IL, interleukin; SRe, super responder. Panel E was previously presented at the International Societies for Investigative Dermatology Congress 2023 and used with permission from Dr Julianty Angsana, PhD. avs W0, P < .001. bQ8W vs Q16W, P < .05. cvs W0 nonlesional skin, P < .001. dvs W0 nonlesional skin, P < .01.
See this image and copyright information in PMC

Comment on

References

    1. Greb JE, Goldminz AM, Elder JT, et al. . Psoriasis. Nat Rev Dis Primers. 2016;2:16082. doi:10.1038/nrdp.2016.82 - DOI - PubMed
    1. Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker JNWN. Psoriasis. Lancet. 2021;397(10281):1301-1315. doi:10.1016/S0140-6736(20)32549-6 - DOI - PubMed
    1. Blauvelt A. Resident memory T cells in psoriasis: key to a cure? J Psoriasis Psoriatic Arthritis. 2022;7(4):157-159. doi:10.1177/24755303221127338 - DOI - PMC - PubMed
    1. Eyerich K, Weisenseel P, Pinter A, et al. . 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. 2021;11(9):e049822. doi:10.1136/bmjopen-2021-049822 - DOI - PMC - PubMed
    1. van der Schoot LS, Baerveldt EM, van Enst WA, et al. . National consensus on biologic dose reduction in psoriasis: a modified eDelphi procedure. J Dermatolog Treat. 2022;2154570:2154570. doi:10.1080/09546634.2022.2154570 - DOI - PubMed

Substances

Associated data