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.

Does the effectiveness of biological medications in the treatment for psoriasis depend on the moment of starting therapy? A preliminary study.

Introduction: It is well known that biological medications acting on selected elements of the immune response are highly effective in psoriasis treatment. It is a common perception that psoriasis is a seasonal disorder with improvement in warmer months, however it has not been unequivocally confirmed. It is not known whether the time of year of starting systematic therapy for psoriasis influences treatment outcomes. Material and methods: Changes in psoriasis severity scores during treatment with biologics were investigated. The scores were recorded for 62 patients with moderate to severe psoriasis at the beginning, after 1, 4 and 7 months of the therapy. Patients were divided into two groups: those beginning the treatment in the cold period of the year (November-March) and in the warm period (May-September). The seasonal groups were also divided into subgroups according to the type of biologics used: interleukin inhibitors and tumor necrosis factor α (TNF-α) inhibitors. Results of the treatment were analysed using standard statistical tests of differences between samples. Results: After 1 and 4 months of the therapy, better efficacy of interleukin inhibitors was found in patients starting treatment in summer. The course of psoriasis improvement in patients taking TNF-α inhibitors resulted in consistent improvement regardless of the season. The outcome of the treatment after 7 months was similar for both seasonal groups and types of biologics used. Conclusions: Our understanding of the effectiveness of the treatments depending on the time of the year combined with the type of biologics used, may further improve results of the therapy.

Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis.

BACKGROUND: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis. METHODS: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18. RESULTS: A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms. CONCLUSIONS: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).

Secukinumab demonstrates superiority over narrow-band ultraviolet B phototherapy in new-onset moderate to severe plaque psoriasis patients: Week 52 results from the STEPIn study.

BACKGROUND: Biologic treatments have been studied mainly in patients with a long-term history of psoriasis and previous treatment failures. OBJECTIVES: The purpose of this primary analysis of the STEPIn study is to determine whether early intervention with secukinumab in patients with new-onset moderate to severe plaque psoriasis is superior to standard of care treatment with narrow band ultraviolet B (nb-UVB) phototherapy. METHODS: The STEPIn study is a randomized, open-label, multicentre study to investigate early intervention with 52 weeks of secukinumab 300 mg administered subcutaneously versus standard treatment with nb-UVB phototherapy in patients with new-onset (≤12 months) moderate to severe plaque psoriasis (NCT03020199). The primary and additional secondary endpoints were ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at Week 52 and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 52, respectively. RESULTS: In the secukinumab and nb-UVB study arms, 77/80 and 76/80 randomized patients received at least one dose of study treatment, respectively. The primary endpoint was achieved: 91.1% (70/77) of patients achieved a PASI 90 response at Week 52 in the secukinumab arm versus 42.3% (32/76) in the nb-UVB arm (p < 0.0001, odds ratio [OR] estimate [95% confidence intervals, CI] = 16.3 [5.6, 46.9]). The additional secondary endpoint was also achieved: 85.7% of patients achieved an IGA 0/1 response at Week 52 in the secukinumab arm versus 36.8% in the nb-UVB arm (p < 0.0001). The safety data were consistent with the safety profiles of secukinumab and nb-UVB with no new or unexpected safety signals. CONCLUSIONS: Secukinumab was superior to nb-UVB in treating patients with new-onset moderate to severe plaque psoriasis. The high and sustained skin clearance observed indicates that biologic treatment for psoriasis may be more effective if used early in the disease course.

Characteristics of pruritus in various clinical variants of psoriasis: Final report of the binational, multicentre, cross-sectional study.

BACKGROUND: Pruritus, which is the most frequent subjective symptom of psoriasis, may cause significant discomfort, embarrassment and even interfere with patients normal daily activities. However, the perception of itch in various psoriasis subtypes remains unknown. OBJECTIVES: The aim of this study was to investigate and to characterize pruritus in different clinical variants of psoriasis. METHODS: This cross-sectional, binational, multicentre study included 295 subjects suffering from nine different clinical subtypes of psoriasis: large-plaque psoriasis (n = 45), nummular psoriasis (n = 32), guttate psoriasis (n = 31), scalp psoriasis (n = 32), inverse psoriasis (n = 23), erythrodermic psoriasis (n = 33), palmoplantar psoriasis vulgaris (n = 33), palmoplantar pustular psoriasis (n = 42) and generalized pustular psoriasis (n = 23). Measures included sociodemographic and anthropometric data, detailed pruritus characteristics including but not limited to pruritus intensity, frequency and extend, as well as psoriasis severity. RESULTS: The lifetime prevalence of pruritus in each clinical variant of psoriasis was similar and quite high, reaching up to 100% in some disease subtypes (i.e., nummular psoriasis, scalp psoriasis and generalized pustular psoriasis). Psoriasis severity correlated with pruritus intensity in scalp psoriasis, palmoplantar pustular psoriasis and generalized pustular psoriasis. The age, duration of psoriasis and BMI did not interfere with the intensity of itch. CONCLUSIONS: Pruritus is highly prevalent in each clinical variant of psoriasis. However, the sensation of itch is very individual, difficult to universally describe even in the same subtype.

Off-label medications in the treatment of hospitalized children with atopic dermatitis.

Introduction: Off-label prescribing is defined as using medications outside conditions of the marketing authorisation including their licensed indications, dosage, age and route. Atopic dermatitis (AD) is the most common chronic skin condition in children which can be related to a high level of off-label prescribing. Aim: To investigate the frequency of off-label prescribing and the medications involved in relation to indications and age in paediatric patients hospitalized for atopic dermatitis in a paediatric dermatology ward in 2019. Material and methods: One hundred and seventy-five consecutive discharge letters of patients were analysed regarding gender, age and medications used during hospital stay and prescribed on discharge. Each medication was checked against the licensed age and indications. Results: Altogether 564 medications were prescribed, including 289 topical and 275 systemic ones with 278 prescribed off-label (49.1%). Out of 289 topical medications, 113 (39.1%) were prescribed off-label regarding indications and 34 (11.76%) regarding the age of the patients. In the systemic medications group, 96 (34.53%) were prescribed off-label as AD was not a registered indication and 35 (12.73%) as the age of the patients was outside the marketing authorization. The most frequent medications prescribed off-label were antihistamines, antibiotics and corticosteroids. Conclusions: Prescribing off-label in paediatric population is a common practice. Both topical and systemic medications are frequently used in AD patients off-label, therefore doctors should be familiar with the pitfalls of prescribing beyond the licensed indications and age.

Concentrations of selected acute phase proteins in patients with chronic venous insufficiency treated with Sulodexide. Part 1.

Introduction: Chronic venous insufficiency (CVI) is a widespread and serious social problem. The pathogenesis of the disease is multifactorial and one of the important factors in its development is inflammation. Aim: Assessment of the concentration of selected acute phase proteins: C-reactive protein (CRP) and α1 antitrypsin (AAT) in the blood serum of patients with CVI before and after treatment with Sulodexide. Material and methods: The study was carried out in 88 people, including 39 clinically healthy subjects as the reference group and 49 patients with CVI at various stages of the disease. The concentrations of CRP and AAT were determined. Results: The concentration of CRP in patients before the use of Sulodexide, compared to the results in the reference group, was statistically significantly higher. The concentration decreased significantly after the applied treatment. AAT concentration was significantly (p < 0.05) higher in the group of patients compared to the reference group. After treatment with Sulodexide, AAT concentration decreased in all study groups, which was statistically significant compared to the reference group. Conclusions: Elevated levels of acute phase proteins: CRP and AAT in patients indicate the participation of the inflammatory component in the pathogenesis of CVI. Monitoring levels of acute phase protein, especially AAT, may be useful in tracking the course of the disease, the body's response to treatment, and in making prognosis. Sulodexide, which acts mainly as an anticoagulant and profibrinolytic, also has an anti-inflammatory effect, which may contribute to the inhibition of the development of subsequent stages of CVI.

Does molecular scarring in psoriasis exist? A review of the literature.

Plaque psoriasis is a chronic inflammatory dermatosis characterized by a tendency to recur in the same locations after discontinuation of treatment. The implementation of therapy with drugs targeting cytokines like interleukin (IL) 17A (IL-17A) and IL-23 has revolutionized the treatment of psoriasis and enabled the achievement of skin without lesions. However, despite the clinical resolution of psoriatic eruptions, cells that maintain the local memory of the disease remain in the dermis and epidermis, constituting a kind of molecular scar. The cells responsible for maintaining memory in the skin of patients and influencing the rapid relapse of the disease after the triggering factor are primarily tissue resident memory T cells (TRM), but it seems that regulatory T lymphocytes (Treg), dendritic cells (DC), and Langerhans cells (LC) may also play an important role in this process. We reviewed the literature to explain the concept of molecular scarring in psoriasis, and to assess the effect of various therapies on immune memory.

Shift in skin microbiota of children with atopic dermatitis after topical gentian violet application.

Introduction: Increasing usage of antimicrobial agents may contribute to bacterial resistance in atopic dermatitis (AD). In this case an alternative topical treatment might be gentian violet (GV), suggested for its antibacterial and antifungal properties. Aim: To assess the microbial composition of lesional skin in children with AD and a control group aged 2-12 years, before and after 3 days of 2% aqueous GV application. Material and methods: Skin samples were taken from 30 AD patients and 30 healthy controls aged 2-12 years. The procedure was done two times - before and after 3 days of 2% aqueous GV application. The material was collected from skin lesions in the cubital fossa using 25 cm2 impression plates, containing CHROMagar Staph aureus and CHROMagar Malassezia. After the incubation period, the grown colonies were counted and identified by the Phoenix BD testing system. Results: The results revealed a statistically significant reduction in total counts of bacteria in both groups of children after GV application (p < 0.05). The significant decrease in the number was seen in Staphylococcus spp. (S. aureus, S. capitis, S. haemolyticus, S. cohnii) in AD patients. The number of Staphylococcus spp. was comparable in patients with AD after GV treatment and healthy patients before GV exposure (p = 1.000). Conclusions: Our study results show that GV does not damage the skin surface ecosystem and allows the reduction of excessive bacterial counts on eczematous lesions to a 'safe' level, similar to that of healthy children.

Comparative effectiveness of adalimumab versus ustekinumab in the treatment of severe chronic plaque psoriasis: The results based on data from the program "treatment of moderate and severe forms of plaque psoriasis (B.47)" of the National Health Fund in Poland.

Biological agents: TNF-α inhibitors, IL-12, and IL-23 blockers, IL-17 inhibitors are used in the treatment of plaque psoriasis. Adalimumab (ADA) is an antibody that binds to TNF-α. Ustekinumab (UST) blocks IL-12 and IL-23. The data obtained from medical records is of exceptional value. The aim of the study was to evaluate the efficacy of ADA and UST during a single 40-week period of biological treatment of patients under the drug program "Treatment of moderate and severe form of plaque psoriasis." The group of 620 adult patients with moderate to severe form of plaque psoriasis, who were unresponsive or had contraindications to the standard treatment were qualified to the drug program. In the evaluated group, 50.64% patients were treated with UST, 49.36% with ADA. The efficacy of treatment was assessed during weeks 0, 4, 16, 28, and 40. At week 16th, PASI75 reached 80.72% patients in ADA treated group, PASI ≥90 54.88%, PASI100 19.6% of patients. In the UST group (week 16th) PASI75 reached 70.38%, PASI90 44.26%, PASI100 15.6% of patients. At week 28th PASI90 and PASI100 were more pronounced in the ADA group than in UST. In addition, the total percentage of PASI improvement was significantly higher in the ADA group (p = 0.0006). The percentage of PASI improvement in week 40 was statistically higher in ADA group compared to UST (p = 0.015). Compared to UST, ADA was clinically more effective during a 40-week observation. Patients receiving ADA achieved PASI75, PASI90, and PASI100 more frequently and faster than those treated with UST. Additionally, ADA improved the quality of life of psoriatic patients more substantially compared to UST.

The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis.

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Pros and cons of using systemic acitretin in the paediatric population.

Acitretin, a synthetic analogue of vitamin A is widely used in dermatology. It has an important role in the treatment of psoriasis and keratinization disorders. In adults its safety and efficacy has been proven in many studies, but there are some concerns regarding the use of acitretin in paediatric population, especially in high doses and as a long-term therapy. In this article we present the main indications of acitretin in children as well as the positive and negative aspects of acitretin treatment in this age population.

The role of inflammasomes in cutaneous pathology.

Inflammasomes are large intracellular multiprotein complexes, which constitute a novel part of the innate immune system. In response to danger signals from pathogens or other harmful agents, inflammasomes assemble resulting in production of the inflammatory cytokines. We discuss recent knowledge of the role of deregulated inflammasome activity in skin pathologies such as autoinflammatory diseases as well as common skin diseases such as psoriasis and atopic dermatitis. We also present an insight into the activation and effector mechanisms of inflammasomes in skin carcinogenesis. The complex influence of inflammasome on cutaneous disorders raises new challenges and opportunities for the treatment of skin diseases.

Increased serum levels of interleukin-17 in patients with alopecia areata and non-segmental vitiligo.

Introduction: Alopecia areata (AA) and vitiligo are both skin diseases of autoimmune origin. AA is characterized by patchy hair loss primarily on the scalp but may involve other areas as well, while vitiligo is caused by the destruction of melanocytes and results in the appearance of white patches on any part of the body. Many facts indicate similar pathogenesis of these diseases. Both dermatoses are associated with frequent coexistence of other autoimmune diseases and share common genetic risk factors. Recent data support the theory of the involvement of IL-17 in the pathogenesis of both AA and vitiligo. Aim: To evaluate and compare the serum levels of interleukin (IL)-17 in patients with AA and non-segmental vitiligo (NSV). To assess whether the pattern of serum cytokine concentration can be associated with clinical details and activity of the disease. Material and methods: A cross-sectional study was conducted on 33 patients with AA, 30 patients with NSV, and 30 healthy controls. Serum levels of IL-17 were determined quantitatively by ELISA method. Results: Our analysis identified a systemic inflammatory signature associated with AA and NSV, characterized by elevated levels of IL-17. The levels of IL-17 did not differ significantly between AA patients and NSV patients. Conclusions: Our results show that AA and vitiligo may share common etiopathogenetic pathways, which suggests the potential of developing targeted therapies for both AA and vitiligo treatment. Imbalance of T cell subpopulations and complex systemic cytokine profiles may contribute to the pathogenesis of AA and vitiligo.

Gut microbiota in alopecia areata.

Introduction: In the past few years, the advancement of 16S rRNA metagenomic analysis sequencing has enabled assessing the impact of gut microbiota on the development of skin disease. Alopecia areata (AA) is a nonscarring hair loss disorder with an unknown etiopathogenesis, however, it is hypothesised that a combination of genetic and environmental factors might be involved. Although numerous studies have shown that the microbiome plays a key role at the beginning of skin diseases, the link between AA and gut dysbiosis remains unclear. Aim: To analyse the intestinal microbiome in patients suffering from AA. Material and methods: The study describes the conceivable involvement of gut microbiota in the unclear pathogenesis of AA. We enrolled 25 patients, over 18 years of age with an active state of AA who donated their stool samples. The samples were examined at the human gut microbial community at the species level by metataxonomic analysis of the full-length 16S V3-V4 sequencing. Results: The four major genera that constitute the microbiome's core are Lachnoclostridium, Bifidobacterium, Streptococcus, and Eubacterium, as well as three major phyla: Firmicutes, Proteobacteria, and Actinobacteria. Firmicutes and Proteobacteria are overrepresented in the microflora, which might suggest a disturbed microflora. Furthermore, the composition of bacterial communities suggests a loss of overall richness and a decrease in taxonomic diversity across all samples. Conclusions: This study describes, for the first time, the characteristics of the gut microbiome in AA patients and may provide new insight into the gut microbiome that may play a role in the development of AA.

The role of heterodimer IL-17-A/F in atopic dermatitis.

Introduction: The importance of multifactorial dysregulation in immune response is well recognised in atopic dermatitis (AD). Th17 family cytokine IL-17 (IL-17A-F) is of significance in both acute and chronic phase of AD. Aim: We analysed the differences between serum levels of IL-17A/F and IL-17A, IL-17-F, IL-13, IL-4, association of rs2275913 IL-17A and rs763780 IL-17F gene polymorphisms in paediatric AD patients and control subjects. Material and methods: We assessed 30 children with AD and 30 healthy patients aged 2-12 years. Eczema Area and Severity Index, Investigator Global Assessment and Scoring Atopic Dermatitis scales were used to analyse the severity of skin lesions in AD patients. Genotyping was performed using PCR and the serum concentrations of IL-17A/F, IL-17A, IL-17F, while IL-13 and IL-4 interleukins were determined by enzyme-linked immuno-sorbent assays (ELISA). Results: The revised median assessment scoring in disease severity showed that the studied AD population had a moderate course of the disease. The obtained results indicated elevated plasma levels of IL-17A/F and IL-17-13 in AD patients with no statistically significance of IL-17A, IL-17F and IL-4 compared to controls. AD duration was positively correlated with IL-13 levels and negatively with IL-17A/F (p < 0.05). Moreover, there was no significant difference between case and control groups in the frequency of genotypes and alleles at rs2275913 IL-17A and rs763780 IL-17F polymorphisms (p > 0.05). Conclusions: This study demonstrates increased levels of IL-17A/F in atopic patients, which is positively correlated with severity of the disease and the early phase of the disease. These results highlight a functional role of this cytokine in the pathogenesis of AD in paediatric patients.

Effectiveness of infliximab biosimilars in the treatment of moderate to severe chronic plaque psoriasis: experience of real-world data from the register of the program "Treatment of moderate and severe forms of plaque psoriasis (B.47)" of the National Health Fund in Poland.

Introduction: Infliximab (IFX) is a monoclonal antibody that binds to and neutralizes TNF-α. IFX (Remicade) was approved by the U.S. Food and Drug Administration in 2006 for the treatment of severe plaque psoriasis. In 2013 two infliximab biosimilars: Remsima and Inflectra were also registered. The introduction of biosimilar drugs is associated with a significant reduction in treatment costs. Aim: To evaluate the efficacy of treatment with biosimilar IFX with non-medical switch option in patients with plaque psoriasis under the drug program "Treatment of moderate and severe plaque psoriasis" of the Ministry of Health in Poland. Material and methods: The group of 91 adult patients with moderate to severe plaque psoriasis, unresponsive or with contraindications to the standard treatment were qualified to the drug program (in 2016-2018). Efficacy of treatment with biosimilar IFX was evaluated using the Psoriasis Area and Severity Index, body surface area and Dermatology Life Quality Index scoring performed at week 0, 14, 46 and 94. Results: The mean change in PASI, DLQI, and BSA scores at week 14 was 89.92%, 93.75% and 90.91%, respectively. By week 14, 83.52% of patients achieved PASI75, 49.45% PASI ≥ 90 and 26.37% PASI100. At week 46, 84.62% of patients achieved PASI75, 54.95% PASI ≥ 90, and 21.98% PASI100. At week 94 of therapy, 80.22% of patients achieved PASI75, 48.35% PASI ≥ 90, and 18.68% PASI100. At week 94 of therapy, PASI100 was maintained by 37.5% of patients who achieved PASI100 at week 14. Conclusions: 94-week therapy with biosimilar infliximab results in high and sustained clinical efficacy in patients with moderate to severe psoriasis.

Real-world evidence on time to relapse of plaque psoriasis after discontinuation of biologic treatment in Poland.

The aim of this study is analysis of time to relapse after discontinuation of biologic treatment and identification of factors associated with risk of relapse. The analysis used real-world data of 705 patients treated with biologic drugs (adalimumab [ADA], ustekinumab, infliximab, and etanercept) in Poland in 2013-2019. Time to relapse was analyzed by Kaplan-Meier estimator. Data was stratified by the number of prior relapses. Determinants of risk to relapse were analyzed with Prentice-Williams-Peterson model. Kaplan-Meier estimate of time to the first relapse was 276 days, to the second relapse was 246 days, to the third relapse was 218 days, and to the fourth relapse was 178 days. In multidimensional analysis statistically significant variables affecting risk of relapse were the following: biologic naivety (hazard ratio [HR] 0.707), ADA (HR 0.787), psoriasis area and severity index at the last follow-up visit (HR 1.049), abnormal hemoglobin level (HR 0.794), and abnormal lymphocyte counts (HR 1.278). The findings of this study suggest that periods to relapse after discontinuation of biologic drugs become shorter with the number of prior relapses experienced by the patient. Ninety-five percentage of observed relapses occurred within 613 days of the end of the first treatment cycle, within 478 of the second cycle and within 351 days of the third cycle.

Psoriasis and Atherosclerosis-Skin, Joints, and Cardiovascular Story of Two Plaques in Relation to the Treatment with Biologics.

It is known that both psoriasis (PSO) limited to the skin and psoriatic arthritis (PSA) increase the risk of cardiovascular complications and atherosclerosis progression by inducing systemic inflammatory response. In recent decades, the introduction of biological medications directed initially against TNF-α and, later, different targets in the inflammatory cascade brought a significant breakthrough in the efficacy of PSO/PSA treatment. In this review, we present and discuss the most recent findings related to the interplay between the genetics and immunology mechanisms involved in PSO and PSA, atherosclerosis and the development of cardiac dysfunction, as well as the current PSO/PSA treatment in view of cardiovascular safety and prognosis.

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review.

Inflammasomes are high-molecular-weight protein complexes that may cleave the two main proinflammatory cytokines, pro-interleukin-1ß and pro-interleukin-18, into active forms, and contribute to psoriasis. Despite recent advances made in the pathogenesis of psoriasis, mainly studied as an autoimmune condition, activation of immune response triggers of psoriasis is still not completely understood. Recently, focus was placed on the role of inflammasomes in the pathogenesis of psoriasis. Multiple types of inhibitors and activators of various inflammasomes, inflammasome-related genes, and genetic susceptibility loci were recognized in psoriasis. In this systemic review, we collect recent and comprehensive evidence from the inflammasomes, NLRP1, NLRP3, and AIM2, in pathogenesis of psoriasis.