Vol 93, No 5 (2017)

Recent studies on psoriasis confirmed that interleukin-17 (IL-17) plays a crucial role in the progression of the disease. Inhibition of this cytokine leads to significant improvement in the course of the disease. Russian biotechnology company BIOCAD have developed an innovative drug, a monoclonal antibody against IL-17, BCD-085. The main objective of the phase II study was to determine the optimal therapeutic dose of BCD-085 in patients with moderate-tosevere plaque psoriasis. The efficacy, safety, and pharmacokinetics of the drug have also been investigated.

Materials and methods

The study was an international multicenter, comparative, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of multiple subcutaneous administration of various doses of BCD-085 to patients with moderate to severe plaque psoriasis. Patients were randomized into 4 groups in 1:1:1:1 ratio: group 1 received BCD-085 at a dose of 40 mg, group 2 – 80 mg, group 3 – 120 mg, and group 4 received placebo. Administration of BCD-085/placebo was performed subcutaneously on day 1 at weeks 0, 1, 2, and then on day 1 at weeks 4, 6, 8, 10.

Results

All studied doses of BCD-085 demonstrated significant superiority over placebo and high efficacy in the treatment of plaque psoriasis. PASI 75 at week 12 was reached by 92.68% of patients in group 3 (120 mg of BCD-085), 83.33% in group 2 (80 mg of BCD-085), 80.0% in group 1 (40 mg of BCD-085), and 23.08% in group 4 (placebo) (p < 0.0001). In the course of the study, the dose-dependent effect of the drug was demonstrated. The drug showed favorable safety profile (no cases of serious adverse events or early withdrawal due to adverse events, no cases of adverse events with 4 grade of severity according to CTCAE 4.03). According to the results of pharmacokinetics study, the drug is characterized by a linear increase in serum BCD-085 concentration, reaching its maximum by the end of the first week of observation, and by slow elimination.

Conclusion

BCD-085 showed high efficiency, more than 90% of patients reached PASI 75 by the 12th week of treatment, and a favorable safety profile. Based on the results of the phase II study, the optimal therapeutic dose was 120 mg.

Aetiology, pathogenesis, clinical and patomorphological criteria for diagnosis of tuberous sclerosis diagnosis are described in this paper. Clinical case of long undiagnosed tuberous sclerosis is presented. 

The psychopathological features of patients with excoriated acne are analysed. An integrative anx-iety test among 43 patients (mean age 24.7±7.1 years) demonstrated borderline values and a high level of personal anxiety in 46.5% of cases; assessment according to the Beck Depression Inventory revealed subdepression among 25.6% and depression among 13.9% of patients; the Global Severity Index (GSI) of the Symptom Checklist-90-R (SCL-90-R) was in the zone of elevated and high val-ues among 31.1% of patients. The greatest deviations from the norm were observed in the areas of interpersonal sensitivity among 34.9% of patients; dev phobic anxiety – 30.2%; paranoia – 30.2%; while somatisation of complaints was observed among 27.9% of patients. The obsessive-compulsive subscale exceeded normative values among 21% of patients. 

Atopic dermatitis is a chronic recurrent inflammatory disease caused, inter alia, by violations of the barrier function of the skin and pathological immune response in the form of an imbalance of Th1 and Th2 lymphocytes with increased production of IL-4, IL-5, IL-13, IL-31. Treatment of severe forms of atopic dermatitis is not an easy task due to the variability of the individual response to treatment, the short duration of the therapeutic effect and the frequent development of undesirable phenomena associated with the use of existing methods of systemic immunosuppressive therapy. The study of the pathogenesis of atopic dermatitis made it possible to identify the spectrum of molecular targets, providing the basis for researching alternative variants to the previously used systemic therapy methods – genetic engineering biological preparations. Contemporary data on the pathogenesis of atopic dermatitis as well as potential molecular targets for innovative biological preparations, the efficacy of which has been evaluated through clinical trials, are presented in the review. 

In the literature review, contemporary data on immune pathogenesis of psoriasis and the emergence of comorbid states against the background of systemic chronic inflammation among patients is discussed. On the example of the apremilast medical preparation, the information on a new class of therapeutic agents for the treatment of psoriasis and psoriatic arthritis – “small molecules” is given, including their physicochemical properties and action mechanism, as well as on the key differences from immune-suppressive and genetically engineered biological preparations. Data on large-scale international randomised clinical trials of the efficacy and safety of the PDE4 inhibitor of apremilast among patients with moderate to severe psoriasis and psoriatic arthritis is presented. The published international clinical recommendations on the use of apremilast among patients with psoriasis and psoriatic arthritis, the criteria for evaluating the response to therapy, as well as the potential profile of patients for the use of apremilast in real clinical practice are discussed.

In the article, issues associated with the study of syphilis propagation among different age groups in the Russian Federation are elucidated along with the incidence dynamics of the clinical forms of syphilis in Russia over the period 2006-2016. The influence of gender factors on the transmission of syphilis in Russia was assessed.