One of the target drugs for plaque psoriasis treatment is apremilast, which is a selective phosphodiesterase 4 (PDE4) inhibitor. In this study, 34 moderate-to-severe and severe plaque psoriasis patients from Russia were treated with apremilast for 26 weeks. This allowed us to observe the effectiveness of splitting patient cohorts based on clinical outcomes, which were assessed using the Psoriasis Area Severity Index (PASI). In total, 14 patients (41%) indicated having an advanced outcome with delta PASI 75 after treatment; 20 patients indicated having moderate or no effects. Genome variability was investigated using the Illumina Infinium Global Screening Array. Genome-wide analysis revealed apremilast therapy clinical outcome associations at three compact genome regions with undefined functions situated on chromosomes 2, 4, and 5, as well as on a single single-nucleotide polymorphism (SNP) on chromosome 23. Pre-selected SNP sets were associated with psoriasis vulgaris analysis, which was used to identify four SNP-associated targeted therapy efficiencies: IL1β (rs1143633), IL4 (IL13) (rs20541), IL23R (rs2201841), and TNFα (rs1800629) genes. Moreover, we showed that the use of the global polygenic risk score allowed for the prediction of onset psoriasis in Russians. Therefore, these results can serve as a starting point for creating a predictive model of apremilast therapy response in the targeted therapy of patients with psoriasis vulgaris.

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Эффективность и безопасность препарата BCD-085оригинального моноклонального антитела против интерлейкина-17 у пациентов со среднетяжелым и тяжелым вульгарным псориазом. Результаты II фазы международного многоцентрового сравнительного рандомизированного двойного слепого плацебо-контролируемого клинического исследования

Objective — Assessment of phosphodiesterase-4 inhibitor (apremilast) therapy’s influence on skin cytokine levels in patients with moderate-to-severe and severe psoriasis. Material and Methods — An open, uncontrolled study was conducted. 16 patients with plaque psoriasis (13 men, 3 women; mean ± standard deviation (SD) age 35.1±9.7 years, range 21-60) were enrolled. The mean Psoriasis Area and Severity Index (PASI) was 20.7±8.93 (range 10-47). All patients were prescribed apremilast 30 milligrams (mg) per os (PO) Bis In Die (BID). The efficacy of therapy was evaluated by PASI at 14 and 26 weeks of therapy. Lesional skin samples were collected at baseline and weeks 14 and 26. Levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL -33, interferon (INF)-γ, Soluble CD40-ligand (sCD40L), tumor necrosis factor (TNF)-α were measured by microsphere-based suspension array technology (Luminex® xMAP™ system). Results — Levels of cytokines (except IL-4 and IL-33) in lesional skin samples were found to have decreased at week 14 compared with those at baseline. Similar decreases were seen for IL-23, IL-25, IL-31, sCD40L at week 26. In contrast, the levels of other cytokines increased again at week 26, in comparison with baseline. Levels of IL-4 and IL-33 rose throughout the follow-up period. Cytokine levels in lesional skin samples were compared with those of healthy controls both at baseline and during therapy. Conclusion — The results of our study show that administering apremilast therapy to patients with psoriasis can bring the levels of cytokines involved in the IL-23/IL-17 axis in the lesional skin to the level of cytokine in non-lesional skin and to the levels in the skin of healthy individuals.

It is considered that pruritus might be either a predisposing factor of development of cutaneous lichen amyloidosis or its symptom. In this case report we try to elucidate this issue. Case of 27-years old patient of Asian origin with cutaneous lichen amyloidosis is presented. Sites of lesions closely matched the scratched areas. Within the affected area there was a melanocytic nevus, which the patient avoided to touch. The area around the nevus was free from amyloidosis lesions. It proves the role of pruritus followed by scratching in the development of cutaneous lichen amyloidosis patches.

Background. Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. The aim of the present study was to produce up-to-date information on different phototherapy approaches on skin cytokines in patients with MF. Methods. A total of 27 patients with mycosis fungoides were treated with phototherapy: NB-UVB (narrow‐band ultraviolet B therapy) (10 patients) and PUVA (long-wavelength ultraviolet radiation of spectrum A with the use of skin-photosensitizing furocoumarins) therapy (17 patients). Evaluation of the effectiveness of treatment was carried out using BSA (body surface area) and the modified assessment of the severity of the skin lesions scale (mSWAT) used to quantify tumor mass in cutaneous T-cell lymphomas. Average numbers of procedures were 30.2 and 27.8 in the NB-UVB and PUVA groups, respectively. The median total dose of NB-UVB irradiation was 19.9 J/cm2 and PUVA therapy was 104.0 J/cm2. The overall response to therapy including complete and partial remission was 74.9% in the total group; 70% in the NB-UVB group, and 77.7% in the PUVA therapy group. In the obtained biopsies from lesions, surrounding tissue before treatment and skin samples of four healthy volunteers, the concentration of the IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L, and TNF-α cytokines was studied. An increase in IL-4 and TNF-α levels was shown in the lesional skin of patients compared to the skin of healthy controls. After the treatment, positive correlations of mSWAT with the levels of IL22, IL33, and TNF-α in the tumor tissue were found. The levels of IL10 and IFN-γ after PUVA treatment were increased in comparison to baseline. There was no difference in cytokine levels before/after NB-UVB therapy.

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