Artikel
Secukinumab study in PSOriasis exploring pruRITUS intensity and lesional biomarkers [PSORITUS]: Subgroup analysis of patients with psoriatic arthritis
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Veröffentlicht: | 4. September 2017 |
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Background: Pruritus is affecting 70-90% of psoriasis (PsO) patients and considerably compromising their Quality of Life. The pathogenesis of pruritus in PsO is not fully understood: Hyper-innervation may be a possible cause for pruritus. Secukinumab (anti-IL-17A) has demonstrated superior efficacy in the treatment of moderate/severe PsO. IL-17A blockade may also promote reconstitution of skin innervation. Therefore, the purpose of this study is to explore the response regarding PsO symptoms, pruritus intensity and lesional biomarkers during Secukinumab treatment and after drug withdrawal.
Methods: PSORITUS is an exploratory clinical study including a 16-week open-label run-in phase (core study) and 16-week placebo-controlled, randomized withdrawal phase. The full analysis set (FAS) comprises 130 patients with PsO of which 18 patients suffered from psoriatic arthritis (PsA). Primary objective of the study is the superiority of Secukinumab (300 mg) vs. placebo on pruritus intensity (VAS 0-100 worst itching within 24 hours) at week 32. Exploratory objectives are the assessment of clinical efficacy of Secukinumab on itch intensity and disease-specific skin lesions as well as lesional and serum biomarkers.
Results: PSORITUS achieved its primary objective with Secukinumab being superior to placebo regarding pruritus intensity in the means of worst itching within 24 hours (FAS, p=0.0055). During the core study, pruritus intensity was reduced under Secukinumab treatment from 81.0 (baseline) to 2.0 (week 16) for all PsO patients. The subgroup of PsA patients presented with less pruritus intensity of 70.5 at baseline which was reduced to 5.0 (week 16; median) under Secukinumab treatment. PASI 90 response was achieved by 77.9% of all PsO patients during the core study whereas 68.8% of the PsA patient population achieved PASI 90 at week 16. In lesional skin samples of PsO patients disease-specific pathologic changes (e.g. Hyper-/Parakeratosis, dilated blood vessels, cellular hyperplasia) turned to normal on treatment with Secukinumab. In addition, serum concentrations of specific biomarkers (e.g. NGF, TrkA) markedly responded to therapy with Secukinumab.
Conclusion: The PSORITUS study showed superiority of Secukinumab compared to placebo in pruritus intensity for PsO patients. A subgroup of PsA patients also clearly improved in pruritus intensity as well as in the PASI 90 response.