A randomized, double-blind, phase III study assessing clinical similarity of SB17 (proposed ustekinumab biosimilar) to reference ustekinumab in subjects with moderate-to-severe plaque psoriasis.

BACKGROUND: Ustekinumab (UST) is a safe and effective treatment for moderate-to-severe psoriasis. OBJECTIVES: To compare efficacy, safety, pharmacokinetics (PK), and immunogenicity of the proposed UST biosimilar SB17 with reference UST in subjects with moderate-to-severe plaque psoriasis. METHODS: In this randomized double-blind study, subjects were randomized to receive 45 mg of SB17 or UST subcutaneously at week 0, 4, and every 12 weeks. The primary endpoint was the percent change from baseline in Psoriasis Area and Severity Index at week 12 with an equivalence margin of [-15%, 15%]. Other secondary efficacy, safety, PK, and immunogenicity endpoints were measured through week 28. RESULTS: Two hundred forty-nine subjects were randomized to SB17, 254 to UST. Adjusted difference of Psoriasis Area and Severity Index change from baseline at week 12 of -0.6% (95% confidence interval; -3.780, 2.579) was within the equivalence margin. Physician's Global Assessment and Dermatology Life Quality Index were also comparable. Overall treatment-emergent adverse events were comparable (SB17: 48.2%, UST: 48.8%). The overall incidence of antidrug antibodies up to Week 28 was 13.3% with SB17 and 39.4% with UST. LIMITATIONS: Data were only through week 28. CONCLUSION: SB17 was clinically biosimilar to UST up to week 28.

[The role of cytokines released by keratinocytes in psoriasis pathogenesis]. / Rola cytokin uwalnianych przez keratynocyty w patogenezie luszczycy.

The paper presents epidemiology, pathogenesis, environmental triggers and types of psoriasis depending on the first psoriatic lesions. The immunological system by cytokines which source are keratinocytes, plays the important role in psoriatic course. The core feature of the disease is increased number of mitotic figures in the basal lamina of the epidermis and accelerated abnormal maturation of keratinocytes. Keratinocyte is the main cell in psoriasis and source of many cytokines. Proinflammatory cytokines and cytokines with inhibitory effect for psoriasis have been described. The authors show results with use of method of blocking cytokines operation (against interleukin TNF alpha) and using of interleukin 4 and interleukin 10 in therapy of psoriasis.

[The latest diagnostical methods and therapy in melanoma]. / Najnowsze metody diagnostyczne i leczenie w czerniaku.

Molecular biology, immunology, diagnostic and treatment of cutaneous melanoma have been analyzed on the basis of current literature due to the increasing frequency of this cancer. Due to the increasing frequency of melanoma it is crucial to detect early the malignant lesions on the basis of physical examination and noninvasive diagnostic methods (dermatoscopy, videodermatoscopy with total body photography). Histopathological examination is conclusive. In diagnostic imaging of early stage melanoma it is very important to evaluate the regional lymph node. In clinical practice, the cross-sectional imaging modalities including computed tomography (CT), ultrasound and magnetic resonance (MR) are widely used to assess lymph nodes. Sentinel lymph node (SLN) biopsy is currenly a valuable and reliable diagnostic procedure for precise staging of patients with clinically no cutaneous melanoma. The presence of SLN metastases is the most important negative factor for clinical outcome in melanoma patients. Introduction of RT-PCR allowed to detect individual cancer cells in tested sample of blood or tissue. Surgical treatment is an essential therapeutic modality in patients with melanoma. Treatment of a primary melanoma involves local excision of the tumour with a margin of skin and subcutaneous tissue. The role of systemic therapy is still a matter of clinical trials. Today's systemic therapy modalities include the use of biological agents (e.g. interferon alfa and interleukin 2) and cytotoxic agents. The efficacy of different types of melanoma vaccines (antigenic, cellular, DNA, GMTV) has been analyzed in numerous clinical trials. Results of these trials are still unsatisfactory. Dendritic cells in melanoma therapy will be very important in the future. Dendritic cells are the most efficient stimulators of T lymphocyte response among professional antygen presenting cells (APC) and the only APC capable to prime naive T lymphocytes with the antygen. A response to weakly immunogenic and tolerogenic tumor antigens can be achived with the use of DC as APC. This review represents an attempt to discuss current evidence on the place of adjuvant and palliative systemic therapy in melanoma.

[Psoriasis and cardio-vascular disorders]. / Luszczyca, a choroby sercowo-naczyniowe.

Psoriasis is one of the most frequent skin diseases. It occurs in adult people with a frequency 2-3%. Psoriasis is a systemic disease with immunologic and genetic determinants. Micro and macro vascular disorders are important for pathogenesis of psoriasis. Authors attempt to show a current scientific statement of pathogenetic mechanisms in psoriasis with special consideration of factors involving cardiovascular abnormalities. In consecutive steps described are associations between psoriasis and arterial hypertension from etiological, pathological and epidemiological point of view. In the same order are reviewed the junctions of psoriasis and lipid and carbohydrate metabolism disorders, as well as coagulative and heart valves abnormalities.