Cytokine Levels of Skin Lesions in Moderate and Severe Psoriasis as Predictors for the Type 4 Fosphodiesterase Inhibitor (Apremilast) Therapy Effectivness

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Abstract


Background. Psoriasis is a widespread skin disorder characterized by cytokines as the main modulators of skin inflammation. A promising psoriasis therapy approach is targeted on cytokine networks by inhibiting the phosphodiesterase 4 (PDE-4). The efficacy and safety of the PDE-4 inhibitor apremilast in psoriasis confirmed in multicenter controlled studies, which, however, are accompanied by reports of unsuccessful therapy cases. Aims — to determine early immunological predictors for PDE-4 inhibitor (apremilast) therapy efficacy based on skin lesions cytokines analyzes in patients with moderate to severe psoriasis. Methods. An open, uncontrolled prospective clinical study was performed. Efficacy of apremilast was analyzed by PASI, BSA, sPGA and DLQI. The outcomes at 26 therapy week were compared with the cytokine levels in skin biopsies selected before starting therapy and analyzed using xMAP technology. The multiparameter prognostic model for apremilast therapy effectiveness was developed based on a heterogeneous sequential recognition procedure. Results. The 34 patients with moderate to severe psoriasis were included in the study. According to the clinical outcomes, two comparison groups were formed: high (75% reduction in PASI score or more; n = 14) and insufficient (50% reduction in PASI score or less; n = 20) apremilast efficiency. Cytokines analyses showed an inverse relationship between the initial anti-inflammatory IL-10 level and the PASI reduction (r = –0.37; p < 0.025). On the other hand, the relationships between pro-inflammatory cytokines IL-1β and IL-6 levels and PASI score at the 26th week of therapy were characterized by positive correlation: r = 0.31 (p < 0.05) and r = 0.37 (p < 0.025), respectively. Based on the data obtained, a predictive model for the apremilast therapy efficiency was developed. The expected predictive values of this model were 86% for a high therapy effectiveness and 60% for an insufficient effectiveness, respectively. Conclusions. The study results for the first time describe the cytokine profiles in the skin lesions in patients, who responded differently to PDE-4 inhibitor therapy. These dada allows to predict the treatment efficacy and give a chance to personalize apremilast usage for the moderate and severe psoriasis treatment.


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About the authors

Alexey A. Kubanov

State Research Centre of Dermatovenerology and Cosmetology

Email: alex@cnikvi.ru
ORCID iD: 0000-0002-7625-0503
SPIN-code: 8771-4990

Russian Federation, Moscow

MD, PhD, Professor, Corresponding Member of the RAS 

Olga G. Artamonova

State Research Centre of Dermatovenerology and Cosmetology

Author for correspondence.
Email: artamonova_olga@list.ru
ORCID iD: 0000-0003-3778-4745
SPIN-code: 3308-3330

Russian Federation, Moscow

Arfenya E. Karamova

State Research Centre of Dermatovenerology and Cosmetology

Email: karamova@cnikvi.ru
ORCID iD: 0000-0003-3805-8489
SPIN-code: 3604-6491

Russian Federation, Moscow

MD, PhD

Elena L. Vasileva

State Research Centre of Dermatovenerology and Cosmetology

Email: elvasileva@cnikvi.ru
ORCID iD: 0000-0002-3580-8398
SPIN-code: 9694-2253

Russian Federation, Moscow

Dmitry G. Deryabin

State Research Centre of Dermatovenerology and Cosmetology

Email: dgderyabin@yandex.ru
ORCID iD: 0000-0002-2495-6694
SPIN-code: 8243-2537

Russian Federation, Moscow

MD, PhD, Professor

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Supplementary files

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1.
Figure: 1. Design of a study aimed at finding early immunological predictors of the effectiveness of therapy with a PDE-4 inhibitor (apremilast)

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2.
Figure: 2. Clinical efficacy of targeted therapy for moderate and severe psoriasis using a phosphodiesterase 4 inhibitor (apremilast): on the abscissa - weeks from the start of therapy; ordinate - the proportion of patients (%) with a change in PASI of 90% (PASI90), 75% (PASI75), 50% (PASI50) or less than 50% (<PASI50) of the initial value of this clinical index

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