ESDR365 - Secukinumab normalizes skin transcriptomes to a never-lesional state in new-onset psoriasis patients more rapidly than in chronic patients

Iversen, Lars; Conrad, Curdin; Kärner, Jaanika; Costanzo, Antonio; Cardner, Mathias; Bier, Katharina; Lohmann, Felix; Frank, Konstantin; Jagiello, Piotr; Ferrero, E.; Eidsmo, Liv; Gaulis, Swann

doi:10.26226/m.62fa009ddcd2c8001911ead5

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“…45 STEPIn demonstrated that early biologic treatment resulted in high levels of sustained skin clearance at W52, 45 and that lesional skin transcriptomes were reverted to a non-lesional state more rapidly in patients with new-onset compared with chronic (≥5 years) psoriasis. 46 Finally, our W28 analysis of GUIDE demonstrated that guselkumab was well tolerated, and no new safety findings were identified.…”

Section: Discussionmentioning

confidence: 89%

“…For example, the STEPIn study is assessing the impact of secukinumab on clinical outcomes and the natural course of disease in patients with new‐onset (≤12 months) psoriasis 45 . STEPIn demonstrated that early biologic treatment resulted in high levels of sustained skin clearance at W52, 45 and that lesional skin transcriptomes were reverted to a non‐lesional state more rapidly in patients with new‐onset compared with chronic (≥5 years) psoriasis 46 …”

Section: Discussionmentioning

confidence: 99%

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Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance (‘clinical super response’): Week 28 results from the ongoing phase IIIb randomized, double‐blind, parallel‐group, GUIDE study

Schäkel

Reich

Asadullah

et al. 2023

Acad Dermatol Venereol

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BackgroundGuselkumab is an interleukin (IL)‐23 inhibitor with demonstrated efficacy in patients with psoriasis.ObjectivesEvaluate the impact of early disease intervention on clinical responses following 28 weeks of guselkumab treatment in patients with moderate‐to‐severe plaque psoriasis. Correlate clinical response and disease duration data with serum biomarker data.MethodsGUIDE is a phase IIIb randomized, double‐blind, parallel‐group, multicentre study of adults with moderate‐to‐severe plaque psoriasis. In study part 1, patients with a short disease duration (SDD [≤2 years]) or a long disease duration (LDD [>2 years]) received guselkumab 100 mg at Week (W) 0, 4, 12, and 20. Those achieving complete skin clearance at W20 and W28 were defined as a super responder (SRe). A multivariable logistic regression analysed the association between baseline factors and the likelihood of becoming an SRe. The relationship between clinical response, disease duration and serum biomarker data was assessed at W0 and 4.ResultsIn total, 880 patients were enrolled (SDD/LDD = 40.6%/59.4% of patients). More SDD than LDD patients achieved absolute Psoriasis Area and Severity Index (PASI) = 0 at W28 (51.8% vs. 39.4%) and were SRes (43.7% vs. 28.1% [overall 34.4%]). SDD patients also achieved PASI = 0 quicker than LDD patients (median 141 vs. 200 days). Disease duration and prior biologic use had the greatest impact on becoming an SRe, with no strong association among these independent variables. At baseline, there were no significant differences in the serum biomarker levels of IL‐17A, IL‐17F, IL‐22 and β‐defensin 2 between SDD and LDD patients, or between SRe and non‐SRe patients. Guselkumab rapidly decreased these markers of systemic inflammation across all patient groups analysed at W4. Guselkumab was well tolerated.ConclusionsGuselkumab efficacy was consistent across subpopulations, on the skin and systemically. The proportion of SRes was higher in SDD than LDD patients, indicating early treatment intervention may improve clinical outcomes.

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Section: Discussionmentioning

confidence: 89%