Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb Study

The occurrence of pruritus in psoriasis was previously underestimated but is a significant burden. Secukinumab (SEC), a monoclonal anti-interleukin-17A antibody, efficiently controls signs of psoriasis, but the effect on pruritus and cutaneous neuroanatomy remained unknown. The primary objective of...

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Main Authors: Lina Renkhold, Manuel P. Pereira, Karin Loser, Dieter Metze, Daniel Baeumer, Nima Melzer, Maximilian Reinhardt, Athanasios Tsianakas, Thomas Luger, Christian Mess, Ruth Becker, Clara Hambüchen, Konstantin Agelopoulos, Sonja Ständer
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Language:English
Published: Medical Journals Sweden 2024-11-01
Series:Acta Dermato-Venereologica
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Online Access:https://medicaljournalssweden.se/actadv/article/view/40737
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author Lina Renkhold
Manuel P. Pereira
Karin Loser
Dieter Metze
Daniel Baeumer
Nima Melzer
Maximilian Reinhardt
Athanasios Tsianakas
Thomas Luger
Christian Mess
Ruth Becker
Clara Hambüchen
Konstantin Agelopoulos
Sonja Ständer
author_facet Lina Renkhold
Manuel P. Pereira
Karin Loser
Dieter Metze
Daniel Baeumer
Nima Melzer
Maximilian Reinhardt
Athanasios Tsianakas
Thomas Luger
Christian Mess
Ruth Becker
Clara Hambüchen
Konstantin Agelopoulos
Sonja Ständer
author_sort Lina Renkhold
collection DOAJ
description The occurrence of pruritus in psoriasis was previously underestimated but is a significant burden. Secukinumab (SEC), a monoclonal anti-interleukin-17A antibody, efficiently controls signs of psoriasis, but the effect on pruritus and cutaneous neuroanatomy remained unknown. The primary objective of this study (NCT02362789) was to evaluate the superiority of SEC treatment vs placebo on pruritus intensity (visual analogue scale; VAS). Furthermore, the treatment-dependent course of pruritus in association with absolute Psoriasis Area Severity Index (PASI) score, as well as cutaneous histopathology and neuroanatomy, was assessed. Open-label SEC 300 mg s.c. was administered regularly until week 16. Patients who reached a ≥ 98% PASI reduction (PASI ≥ 98) were randomized to receive either placebo or SEC up to week 32. Punch biopsies were collected from lesional psoriatic (baseline, weeks 16 and 32) and non-lesional (baseline) skin for histopathological and neuroanatomical analyses. VAS scores improved significantly after open-label SEC treatment but relapsed upon placebo (29.92 ± 33.8) compared with SEC (12.30 ± 22.6; p = 0.036). After SEC-dependent improvement in PASI, histopathology, marker expression and neuroanatomy, relapse was observed with treatment discontinuation in all parameters except neuroanatomy. SEC was superior to placebo by efficiently controlling reduced pruritus intensity, clinically normalizing skin lesions, and reversing histopathological abnormalities. The neuroanatomy recovered upon SEC and remained stable even after withdrawal.
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spelling doaj-art-be7c76688d574b3cbb0b60bd456fa8082024-11-20T14:31:04ZengMedical Journals SwedenActa Dermato-Venereologica0001-55551651-20572024-11-0110410.2340/actadv.v104.40737Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb StudyLina Renkhold0https://orcid.org/0000-0002-3187-0602Manuel P. Pereira1https://orcid.org/0000-0001-5649-2698Karin Loser2https://orcid.org/0000-0002-0007-0936Dieter Metze3Daniel Baeumer4https://orcid.org/0000-0003-4236-4438Nima Melzer5Maximilian Reinhardt6Athanasios Tsianakas7https://orcid.org/0000-0003-1563-7402Thomas Luger8https://orcid.org/0000-0003-1397-1626Christian Mess9https://orcid.org/0000-0001-8642-5226Ruth Becker10Clara Hambüchen11Konstantin Agelopoulos12https://orcid.org/0000-0002-5601-9195Sonja Ständer13https://orcid.org/0000-0003-3612-77861Department of Dermatology, University Hospital Münster, Münster, Germany; Center for Chronic Pruritus, University Hospital Münster, Münster, GermanyInstitute of Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, GermanyInstitute of Immunology, University of Oldenburg, Oldenburg, GermanyDepartment of Dermatology, University Hospital Münster, Münster, GermanyNovartis Pharma GmbH, Nuremberg, GermanyNovartis Pharma GmbH, Nuremberg, GermanyNovartis Pharma AG, Basel, SwitzerlandFachklinik Bad Bentheim, Department of Dermatology, Bad Bentheim, GermanyDepartment of Dermatology, University Hospital Münster, Münster, GermanyDepartment of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany1Department of Dermatology, University Hospital Münster, Münster, Germany; Center for Chronic Pruritus, University Hospital Münster, Münster, Germany1Department of Dermatology, University Hospital Münster, Münster, Germany; Center for Chronic Pruritus, University Hospital Münster, Münster, Germany1Department of Dermatology, University Hospital Münster, Münster, Germany; Center for Chronic Pruritus, University Hospital Münster, Münster, Germany1Department of Dermatology, University Hospital Münster, Münster, Germany; Center for Chronic Pruritus, University Hospital Münster, Münster, GermanyThe occurrence of pruritus in psoriasis was previously underestimated but is a significant burden. Secukinumab (SEC), a monoclonal anti-interleukin-17A antibody, efficiently controls signs of psoriasis, but the effect on pruritus and cutaneous neuroanatomy remained unknown. The primary objective of this study (NCT02362789) was to evaluate the superiority of SEC treatment vs placebo on pruritus intensity (visual analogue scale; VAS). Furthermore, the treatment-dependent course of pruritus in association with absolute Psoriasis Area Severity Index (PASI) score, as well as cutaneous histopathology and neuroanatomy, was assessed. Open-label SEC 300 mg s.c. was administered regularly until week 16. Patients who reached a ≥ 98% PASI reduction (PASI ≥ 98) were randomized to receive either placebo or SEC up to week 32. Punch biopsies were collected from lesional psoriatic (baseline, weeks 16 and 32) and non-lesional (baseline) skin for histopathological and neuroanatomical analyses. VAS scores improved significantly after open-label SEC treatment but relapsed upon placebo (29.92 ± 33.8) compared with SEC (12.30 ± 22.6; p = 0.036). After SEC-dependent improvement in PASI, histopathology, marker expression and neuroanatomy, relapse was observed with treatment discontinuation in all parameters except neuroanatomy. SEC was superior to placebo by efficiently controlling reduced pruritus intensity, clinically normalizing skin lesions, and reversing histopathological abnormalities. The neuroanatomy recovered upon SEC and remained stable even after withdrawal. https://medicaljournalssweden.se/actadv/article/view/40737PruritusPsoriasisNeuroanatomyTherapy
spellingShingle Lina Renkhold
Manuel P. Pereira
Karin Loser
Dieter Metze
Daniel Baeumer
Nima Melzer
Maximilian Reinhardt
Athanasios Tsianakas
Thomas Luger
Christian Mess
Ruth Becker
Clara Hambüchen
Konstantin Agelopoulos
Sonja Ständer
Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb Study
Acta Dermato-Venereologica
Pruritus
Psoriasis
Neuroanatomy
Therapy
title Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb Study
title_full Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb Study
title_fullStr Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb Study
title_full_unstemmed Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb Study
title_short Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb Study
title_sort secukinumab reduces psoriasis associated pruritus and regenerates the cutaneous nerve architecture results from psoritus a doubleblind placebo controlled randomized withdrawal phase iiib study
topic Pruritus
Psoriasis
Neuroanatomy
Therapy
url https://medicaljournalssweden.se/actadv/article/view/40737
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