Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study.

BACKGROUND: CT-P43 is a candidate ustekinumab biosimilar in clinical development. OBJECTIVES: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis. METHODS: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here. RESULTS: In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI -0.23, 4.32) and 0.94 (95% CI -2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43. CONCLUSIONS: CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020.

Psychologic interventions in patients with the chronic dermatologic itch in atopic dermatitis and psoriasis: A step forward with family constellations seminars.

Chronic itch is a complex psychophysiological sensation, which can severely affect the quality of life in patients with atopic dermatitis and psoriasis. Itch depends on the irritation of receptors in the skin and the processing of sensory information in the central nervous system. Severe itch leads to activation and later on to disruption of the stress response, resulting in disorders of skin repair, functional and microstructural changes in the areas of the central nervous system that are responsible for the perception of itch. Psychosocial stress can be an essential factor, activating neurohumoral mechanisms which lead to increased itch and scratch, exacerbating skin damage. Patients with chronic itch often have sleep disorders, increased irritability, and depletion of the nervous system. They are characterized by disrupting social relationships, high incidence of anxiety, depressive disorders, and suicidal tendencies. Psychological methods of intervention can effectively influence various mechanisms in the pathogenesis of itch and scratch and improve social functioning in patients with chronic dermatological itch. In this mini-review, we discuss family constellation seminars as an effective method of psychological intervention that can reduce the intensity of itch, and improve sleep and performance in patients with atopic dermatitis and psoriasis. This method is insufficiently described in previous reviews of psychological interventions in atopic dermatitis and psoriasis patients. The positive impact of family constellations seminars in patients with chronic dermatological itch may be related to reducing stress by improving understanding of the family situation, appropriate management of family secrets, and enhancing interactions with the social environment.

SPECIFICS OF THE ECZEMA PATIENTS` IMMUNE SYSTEM DEPENDING ON THE CLINICAL COURSE OF DERMATOSIS.

OBJECTIVE: The aim: Definition of the systemic immunity cellular components and autoimmune factor in eczema patients depending on the clinical manifestations of dermatosis. PATIENTS AND METHODS: Materials and methods: The study involved 95 eczema patients. 29 of them were diagnosed the true dermatosis form, while 39 and 27 subjects had infectious (microbial) and infectious (mycotic) form of the disease, accordingly. The control group consisted of 30 healthy individuals. CD3+, CD4+, CD8+, CD16 +, CD22 + and CD 95+ cells and autoantibodies to TPO and TG were counted. RESULTS: Results: The eczema patients present uniform, but somewhat labile changes in the state of the immune system. For example, cellular disorders, except for CD8+ count, do not statistically significantly depend on the clinical form of dermatosis, the severity of inflammatory process, and the duration of the disease. At the same time, the decrease of CD8+ count in infectious (mycotic) form of the disease and in acute and subacute course reflects a certain variability of changes in cellular immunity with intact values in true and infectious (microbial) genesis and chronic manifestations of eczema. CONCLUSION: Conclusions: Eczema patients should be subjected to valuation of cellular components of the systemic immunity and autoimmune profile. The CD8 + count of eczema patients can serve as one of the "conditional markers" of a degree of involvement of systemic immunity in the progression of eczema. Therapy of eczema patients should include medicines that possess a wide range of immunomodulatory effect.

Skin microbial landscape and immune-endocrine parameters in patients with psoriasis by using narrowband UVB phototherapy.

OBJECTIVE: The aim: The study of skin microbial landscape and immune-endocrine parameters as well as improvement of treatment efficiency in patients with different clinical course of psoriasis by using narrowband UVB phototherapy. PATIENTS AND METHODS: Materials and methods: We examined 89 patients with psoriasis (51 men and 38 women) aged 18-60. The comparison group consisted of 43 psoriasis patients comparable by age, sex and clinical course with those from the main group (46 patients). Cytokine levels IL-4, IL-8, IL-10, TNFα, thyroid peroxidase (TPO) and thyroglobulin (Tg) autoantibodies and microbial flora of skin were determined in patients with psoriasis. RESULTS: Results: The study finds that conventional therapy does not have sufficient corrective impact on immune-endocrine disorders and the use of narrow-band light therapy has shown that it has a focused corrective impact on cytokine production and modulating effect on the level of TPO and Tg autoantibodies and the state of skin automicroflora of lesions in patients suffering from psoriasis. CONCLUSION: Conclusions: Using UVB (311 nm) therapy in patients with psoriasis allows improving efficiency of treatment and limiting clinical signs in the form of achieving remission and significant improvement in patients' health without any negative dynamic changes.

An alternative diagnostic method of eruptive vellus hair cysts: Report of a familial case with pruritus.

Eruptive vellus hair cysts (EVHC) represent a developmental abnormality of vellus hair follicles. Up till now more than 150 cases of EVHC have been published in the literature, but it appears to be more common than recognized. The diagnostic hallmark is the presence of vellus hair shafts within the cystic space. Firstly to evaluate the potential benefit of new diagnostic method of EVHC using a dermatoscope and secondly to report a familial case of EVHC where females were only affected. Five women from the same family with a clinical diagnosis of EVHC were included in the study. The diagnosis of EVHC was confirmed by skin biopsy with histologic examination in four patients. New diagnostic approach of the cyst contents examination with using a handheld dermatoscope was performed in all patients. Numerous vellus hair shafts were detected on the images of the cysts content taken with dermatoscope and applying the above-mentioned method in all patients. We suggest that it seems possible to differentiate EVHC by using the dermatoscope, which appears to be simple, quick, and less time consuming.

Effects of family constellation seminars on itch in patients with atopic dermatitis and psoriasis: A patient preference controlled trial.

Family dynamics play a major role in itch related dermatoses. The aim of the study was to evaluate the effectiveness of family constellation seminars (FCS) in the decrease of itch in atopic dermatitis (AD) and psoriasis. Thirty-one adult patients with chronic itch (16 with AD and 15 with psoriasis) were allocated to intervention group (FCS + G) and control group (CG). Patients from FCS + G have participated in a series of four FCS for 3 months. During the study period, all patients used only emollients. Itch was evaluated by 27-item questionnaire and skin condition was evaluated by SCORAD and PASI. The severity of itch in FCS + G decreased (Median; (25%;75%)) from 8.42 (6.57;11.92) initially to 4.78 (1.36;9.14); p < .01 after 1 month and (0.61 (0;6.66); p < .001) after 9 months after the psychological intervention with no significant changes in the CG. In the patients with AD in the FCS + G, SCORAD decreased (21.5 (14.4;40); 14.1 (7.3;15.5) p < .05; 7.2 (3.6;11); p < .05). In the FCS + G, itch decreased both in patients with AD and psoriasis, with less significant visible changes of skin in patients with psoriasis. Participation in FCS in a series of four seminars has high effect (r = .53) on reduction of itch and high effect (r = .74) on improvement of AD signs with lower effect on skin condition in patients with psoriasis for 4 months. Positive effect of FCS gradually increases during at least 9 months. Further studies for understanding FCS influence on the patients with itch are needed.