Plaque Psoriasis Patients Research Articles

P51 Plaque psoriasis patients with psoriatic arthritis demonstrate a reduced regulatory capacity for neutrophil elastase compared with plaque psoriasis patients without arthritis

Abstract Identifying which patients with psoriasis (PsO) may develop psoriatic arthritis (PsA) is a research priority. We have previously shown that Elafin along with IL-36g are excellent cutaneous biomarkers for PsO. The protease inhibitor Elafin and its target protease, neutrophil elastase (NE), can be detected in both serum and epidermal samples. Our aims were to assess if known PsO biomarkers are expressed differentially in patients affected by plaque PsO with and without PsA. Protein expression of NE and Elafin were analysed in matched epidermal samples and serum of PsO, PsA patients and healthy controls. Findings were validated in independent PsA and arthritis cohorts. The ratio between NE and Elafin differed significantly between PsO and PsA patients. Expression of elafin was reduced in PsA samples as compared with plaque PsO patients. The ratio of NE to secretory leukocyte protease inhibitor was also increased in PsA as compared with PsO patients with no PsA, healthy controls and other arthritis patients. PsA patients show a reduced NE inhibitor expression in both the skin and blood compartment compared with those with plaque PsO only. This may suggest differences in the ability to regulate neutrophil activity in PsA patients.

P82 Are nail, scalp and intergluteal cleft psoriasis really risk factors for psoriatic arthritis or are we just repeating previous studies?

Abstract Psoriasis is a chronic, inflammatory, immune-mediated, systemic disease that primarily affects the skin and joints. In ∼70% of cases, the skin comes before the joints, and it is believed that ∼30% of patients with psoriasis will develop psoriatic arthritis (PsA). There is an ongoing effort to identify screening tools and biomarkers that detect joint disease early. Known risk factors include early onset and severity of disease, nail, scalp and intergluteal cleft involvement, family history of PsA, HLA-B27 positive, obesity, uveitis, biomechanical stress, and trauma. Observational, cross-sectional study with severe plaque psoriasis patients, aged between 18 and 70 years, of both genders. Non-probabilistic convenience sample: All patients were evaluated by the same board-certified dermatologist. Over 3 months, during the weekly shift of the severe psoriasis clinic, PEST was applied. Clinical and epidemiological variables were collected on medical records. PsA was defined by CASPAR criteria. It underwent an ethical assessment and was approved. Hundred and fifty-eight patients were studied: average age of 50.84 years, with a predominance of females (53.2%). The average duration of the disease was 15.89 years. Mean psoriasis area and severity index and body surface area were, respectively, 16.65 and 20.88%. Fifty patients (31.6%) with PsA were identified. Regarding PEST, a sensitivity of 84.61%, a specificity of 75.47%, with a negative predictive value of 90.90% were identified. Having a positive PEST made the presence of PsA almost seven times more frequent [PR: 6.914, P < 0.0001, 95% confidence interval (CI) = 3.486–13.714]. Scalp (80.9%) and intertriginous/intergluteal cleft psoriasis (55.1%) was frequent in the sample, but did not correlate with the presence of PsA (PR: 1.113, P = 0.794, 95% CI = 0.523–2.454; and PR: 0.881, P = 0.612, 95% CI = 0.565–1.375, respectively). However, nail involvement was significantly related to PsA (PR: 1.669, P = 0.026, 95% CI = 1.071–2.601). PEST performance was consistent with the literature and was especially valuable in ruling out PsA due to its high negative predictive value. A classic study that correlates the involvement of specific sites with joint disease may present a selection bias, since it was conducted within the scope of rheumatology, focusing on patients with seronegative chronic inflammatory arthritis, where the diagnosis of psoriasis was not obvious, being sought in ‘hidden’ areas. After all, apart from the involvement of the nail matrix as an extension of distal interphalangeal enthesitis, what would be the biological relationship between the involvement of the scalp or even the intergluteal cleft and the presence of arthritis? Small sample, cross-sectional design and the fact that only 66% of patients with PsA had the opportunity to confirm their diagnosis with a rheumatologist are recognized limitations.

A large-scale retrospective study in China explores risk factors for disease severity in plaque psoriasis

Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 – May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 – January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848–0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836–0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868–0.953) and 0.951 (95% CI: 0.924–0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the “DELPHI” consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI ≥ 10). “Nomogram-10” provides clinicians with a practical tool to develop personalized intervention strategies based on an individual’s risk profile.Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852.

Real-World Data on Brodalumab Treatment in Patients with Moderate-to-Severe Plaque Psoriasis: An Observational Study from the Czech Republic BIOREP Registry.

The aim of this observational, multicenter study was to assess the real-world use of brodalumab for the treatment of moderate-to-severe plaque psoriasis in patients in the Czech Republic, using data from the BIOREP registry. The study included 273 patients aged≥18years with moderate-to-severe psoriasis who received brodalumab. Endpoints were drug survival (time from treatment initiation to discontinuation), effectiveness [Psoriasis Area and Severity Index (PASI)], and health-related quality-of-life [Dermatology Life Quality Index (DLQI)]. Predicted drug survival probability was 92.4% [95% confidence interval (CI): 89.1, 95.7%] at 6months and 84.2% (95% CI 79.5, 89.1%) at 12months; this was maintained at 24months [80.4% (95% CI 74.5, 86.8%)]. Younger age, higher body mass index, and no previous biologic treatment were significantly associated with longer drug survival. Absolute PASI≤3 after 3months was achieved by 89.8% of patients; 92.4%, 77.8%, and 59.1% reached PASI 75, PASI 90, and PASI 100, respectively. After 12months, 96.5% of 141 patients had an absolute PASI≤3. The proportion of patients achieving DLQI 0/1 was 87.3% at 12months. This study demonstrated high and sustained drug survival with high rates of skin clearance and improved quality of life in patients with relatively severe disease treated with brodalumab. Improvements were observed as early as 3months post-treatment initiation and were sustained for up to 24months in a real-life setting.

High-frequency ultrasonography for the detection of subclinical arthritis in chronic plaque psoriasis patients - A cross-sectional study.

Background Psoriatic arthritis (PsA) is seen in almost 30-40% cases of psoriasis. Psoriasis precedes the onset of PsA in 85% of cases. Delay in the diagnosis of PsA may lead to poor functional outcomes and morbidity. Screening psoriasis patients with high-frequency ultrasound helps to diagnose arthritis at an early stage leading to prompt intervention and possible reduction in the morbidity associated with the disease. Objectives To determine the role of high frequency ultrasonography (USG) in the detection of subclinical PsA. Methods A cross-sectional study was conducted in a dermatology and radiology department of Armed Forces Medical College, Pune between July 2021 and December 2022. Patients of chronic plaque psoriasis with no clinical evidence of arthritis were assessed using high-frequency USG. Various parameters such as bony erosions, synovial thickening, tendon thickening, tendon hypo-echogenicity, calcifications and power doppler signals were assessed. Results A total of 117 patients were included in the study. The distal interphalangeal joint (DIP) and Achilles tendon were the most commonly affected sites. Synovial thickening in DIP was observed in 67 (57%) patients and Achilles tendon thickening was observed in 39 (33%) patients. Limitations of the study The cross-sectional nature of the study is the major limitation. A longitudinal study will be required to understand the clinical relevance of ultrasonographic changes in these patients. Another limitation of the study is the lack of age and gender-matched controls. Future research should include such controls to ensure more accurate results. Conclusion Subclinical arthritis is common in patients with chronic plaque psoriasis. High-frequency ultrasound is a useful tool for detecting subclinical synovitis and enthesitis in asymptomatic patients. The DIP joint and Achilles tendon ultrasound can be used for screening for early detection of PsA.

Comparative effectiveness of combined biologic agents versus standard therapies in the treatment of plaque psoriasis: a retrospective analysis.

Plaque psoriasis is a persistent skin disorder that necessitates efficient management. This study investigates the therapeutic effectiveness and timeline for skin lesion resolution in plaque psoriasis patients treated with combined biologic agents compared to standard therapies. Conducted retrospectively between March 2020 and March 2023, the study included 162 patients with moderate to severe plaque psoriasis. Participants were divided into two groups: the Control Group, which received standard treatments, and the Combined Biologic Agent Group, which received additional biologic therapy with secukinumab. Participants in the Control Group received standard treatments, while those in the Combined Biologic Agent Group received standard treatments plus secukinumab. The results showed that the Combined Biologic Agent Group experienced a significantly faster onset of therapeutic effects, with an average time of 3.04 ± 2.25 days compared to 6.12 ± 2.06 days in the Control Group. Additionally, skin lesion resolution occurred more rapidly in the biologic agent group (7.04 ± 2.13 days) than in the control group (14.56 ± 4.73 days). By week 24, the Psoriasis Area and Severity Index (PASI) scores demonstrated a more substantial reduction in the biologic agent group, decreasing from 26.98 ± 11.28 to 2.48 ± 3.01, whereas the control group showed a reduction from 25.82 ± 10.47 to 10.40 ± 7.63. The overall effectiveness rate was higher in the biologic agent group, with no cases of ineffectiveness, compared to a 20.99% ineffectiveness rate in the control group. Furthermore, there was no recurrence of the disease in the biologic agent group, while the control group experienced an 11.11% recurrence rate. Both groups had a similar incidence of adverse reactions, indicating that the addition of biologic agents does not significantly increase the risk of adverse events. These findings suggest that combined biologic agent therapy offers a more effective and faster treatment option for plaque psoriasis without compromising safety. However, larger-scale clinical trials are necessary to validate these results and establish the long-term benefits and safety of this treatment approach in diverse patient populations.

Oral microbiota diversity in moderate to severe plaque psoriasis, nail psoriasis and psoriatic arthritis

Gaining a comprehensive understanding of the role played by the oral microbiome in moderate to severe plaque psoriasis and its potential implications for disease management and development holds significant importance. With the objective of exploring correlations between the oral microbiota and severe psoriasis, this study involved 72 severe psoriasis patients and 16 healthy individuals, whose clinical manifestations and living habits were carefully recorded. Cutting-edge techniques such as 16S rRNA gene sequencing and bioinformatics analysis were employed to compare the microbial flora, investigating dynamic changes among severe plaque psoriasis patients, psoriatic arthritis patients and healthy individuals. The findings revealed noteworthy patterns including increased levels of Aggregatibacter in the psoriatic arthritis group, accompanied by a decrease in the level of Prevotella. Moreover, the enrichment o Capnocytandophaga (P = 0.009), Campylobacter (P = 0.0022), and Acetobacter (P = 0.0292) was notably more substantial in the psoriasis group compared to the control group, whereas certain bacterial species such as Bacteroides (P = 0.0049), Muribaculaceae (P = 0.0048) demonstrated decreased enrichment. Additionally, the psoriatic arthritis group exhibited significantly higher levels of Ralstonia, Bifidobacterium and Micromonospora. Based on these findings, it can be inferred that individuals with lower levels of Prevotella and higher levels of Corynebacterium may be more susceptible to psoriasis exacerbation.

Persistence of advanced systemic pharmacological treatment of moderate-to-severe psoriasis among bio-naïve patients-A retrospective register-based cohort study in Finland and Sweden.

Plaque psoriasis (PsO) requires long-term treatment for symptom control and remission; thus, a long-term pharmacological intervention is necessary. Treatment persistence reflects long-term therapeutic effectiveness and tolerance. This study investigates drug persistence and compares treatment discontinuation rates across biologic agents and apremilast used by PsO patients in Finland and Sweden. This retrospective register-based cohort study included bio-naïve patients (≥18 years) with moderate-to-severe PsO, who initiated treatment with abatacept, adalimumab, brodalumab, certolizumab pegol, etanercept, golimumab, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab, ustekinumab or apremilast during 2008-2020 in Finland or Sweden. The main analysis evaluated persistence (based on duration of continuous treatment) and compared rates of treatment discontinuation using guselkumab as reference drug, during 2018-2020 in Finland. Treatment discontinuation was assessed by survival analysis of the time to first drug discontinuation, including switching to other study drugs. Due to limited sample size (n < 20), certain biologics (abatacept, brodalumab, certolizumab pegol, etanercept, golimumab, risankizumab and tildrakizumab) were excluded from the persistence analysis. In Finland, 709 patients fulfilled the inclusion criteria during 2018-2020 for the main analysis. The highest persistence was observed for guselkumab and ustekinumab with 90 and 85% of treated patients, respectively, continuing treatment for ≥1 year. Comparable results were observed in the expanded cohort analysis (index starting in 2008; 2745 bio-naïve patients in Finland and 10,970 in Sweden). Furthermore, patients treated with guselkumab in Finland showed lower treatment discontinuation rates compared to other study drugs. Guselkumab and ustekinumab demonstrated high persistence as measured by continued treatment for at least 1 year. Furthermore, these treatments demonstrated lower rates of discontinuation compared to other study drugs included in the analysis. Understanding the balance between efficacy and feasibility in treatment decisions is crucial, as feasibility may impact persistency outcomes and potentially increase persistency rates.

Benefits Over Five Years of Ixekizumab Treatment in Patients With Psoriasis Involving Challenging Body Areas.

Psoriasis involving challenging body areas, such as the scalp, face, palmoplantar surfaces, or nails, can be challenging to treat and negatively affects patient outcomes. To assess clear responses and cumulative clinical benefits over 5 years of ixekizumab treatment of moderate-to-severe plaque psoriasis in patients with and without baseline involvement of challenging body areas. This post hoc analysis included patients treated with ixekizumab in the UNCOVER-3 trial. We assessed PASI100 responses through the week (W) 264 and cumulative clinical benefits at W264 (calculated as least-squares mean of the percentage of maximum area under the curve for PASI100 and PASI% improvement and expressed as cumulative clearance days). Statistical differences were calculated via ANCOVA. A total of 385 patients were analyzed: 349 with scalp involvement, 152 with facial involvement, 96 with palmoplantar involvement, and 229 with nail involvement. Proportions of patients achieving PASI100 were numerically similar between patients with and without scalp and nail involvement. More patients without facial and palmoplantar involvement achieved PASI100 at W60 (only palmoplantar), W108, W156, W204, and W264 (only palmoplantar). At W264, cumulative clinical benefits for PASI100 and PASI% improvement were high and similar in both patient groups, with and without challenging body areas. A significant difference (P=0.006) was only observed for PASI% improvement between patients with and without nail involvement. For most efficacy measures, patients treated with ixekizumab over 5 years achieved similar clear responses and cumulative clinical benefits regardless of baseline involvement of challenging body areas. J Drugs Dermatol. 2024;23(8):619-625.&nbsp; doi:10.36849/JDD.8160.

Guselkumab treatment normalizes the stratum corneum ceramide profile and alleviates barrier dysfunction in psoriasis: results of a randomized controlled trial

The epidermal inflammation associated with psoriasis drives skin barrier perturbations. The skin barrier is primarily located in stratum corneum (SC). Its function depends on the SC lipid matrix of which ceramides constitute important components. Changes in the ceramide profile directly correlate to barrier function. In this study, we characterized the dynamics of the barrier function and ceramide profile of psoriatic skin during anti-Interleukin-23 therapy with guselkumab. We conducted a double-blind, randomized controlled trial in which 26 mild-to-severe plaque psoriasis patients were randomization 3:1–100 mg guselkumab or placebo for 16 weeks and barrier dynamics monitored throughout. Barrier function was measured by trans-epidermal water loss measurements. Untargeted ceramide profiling was performed using liquid chromatography-mass spectrometry after SC was harvested using tape-stripping. The barrier function and ceramide profile of lesional skin normalized to that of controls during treatment with guselkumab, but not placebo. This resulted in significant differences compared to placebo at the end of the treatment. Changes in the lesional ceramide profile during treatment correlated with barrier function and target lesion severity. Nonlesional skin remained similar throughout treatment. Guselkumab therapy restored the skin barrier in psoriasis. Concomitant correlations between skin barrier function, the ceramide profile, and disease severity demonstrate their interdependency.

Disease severity in moderate‐to‐severe plaque psoriasis: Results from the Belgian REDISCOVER study

AbstractBackgroundIn the Belgian DISCOVER study, conducted in 2011–2012 before the advent of the IL‐17 and IL‐23 Inhibitors, significant undertreatment of patients with plaque psoriasis was reported.ObjectivesThe present study aimed to re‐evaluate the real‐world clinical management and quality of care of moderate‐to‐severe plaque psoriasis patients treated with systemic treatment for at least 24 weeks in clinical practice in Belgium.MethodsThis cross‐sectional and retrospective chart review (REDISCOVER) was conducted in 2021–2022 in private practices and hospitals in Belgium. Patient data were collected during one single visit and included assessments of psoriasis severity (Psoriasis Area Severity Index [PASI], Body Surface Area [BSA], Pruritus VAS scale) and Health‐Related Quality of Life (Dermatology Life Quality Index [DLQI]) and other selected criteria of the Belgian treat‐to‐target (T2T) outcome set.ResultsOf the 306 patients included in the study, 81.4% received treatment with biologicals and 18.6% with traditional systemics, that is, methotrexate or apremilast. IL‐23 Inhibitors (33.7%) and methotrexate (10.8%) were the most prescribed biologicals and traditional systemic, respectively. Between the time of treatment initiation and enrolment, the average PASI and BSA scores decreased, indicating treatment benefits. PASI scores were lower in patients treated with biologicals versus patients treated with traditional systemics. Full achievement of the two Belgian T2T guidelines dimensions was observed in 51% of the patients. Nonetheless, patients were generally satisfied with their treatment (96.1%) and physicians evaluated the treatment as adequate for most patients (87.3%).ConclusionsCompared to 10 years ago, a demonstrable improvement in care of moderate‐to‐severe psoriasis patients was observed in Belgium. This was reflected by substantial achievement of the current treatment goals and high treatment satisfaction by both patients and physicians. While one out of five patients is not achieving targeted goals, and is not treated with a biological, it seems there is still room for improvement.

Significant Correlation Between Cutaneous Abundance of Streptococcus and Psoriasis Severity in Patients with FBXL19 Gene Variants.

Psoriasis results from both genetic predisposition and environmental triggers, such as Streptococcal infections. This study aimed to explore the correlation between the abundance of the Streptococcus genus on the skin and psoriasis severity in individuals carrying specific psoriasis-associated genetic variants. Studying 39 chronic plaque psoriasis patients, the elbow skin microbiome and 49 psoriasis-related single nucleotide polymorphisms (SNPs) were analysed using a MiSeq instrument for 16S rDNA sequencing, and CLC Genomic Workbench for processing and analysis. Through multivariate linear regression analysis, a positive correlation was found between Streptococcus genus abundance and psoriasis severity in patients with certain FBXL19 gene-related heterozygous SNPs (rs12924903, rs10782001, rs12445568). Conversely, a negative association was observed in patients with homozygous genotypes. Moreover, we identified an association between Streptococcus abundance and psoriasis severity in patients with genetic variants related to IL-22, ERAP1, NOS2, and ILF3. This is the first study highlighting a positive association between Streptococcus skin colonization and psoriasis severity in patients with heterozygous genotypes within the FBXL19 gene region. FXBL19 targets the IL-33/IL1RL1 axis, crucial in infectious diseases and innate immunity promotion. These novel results suggests an intricate interaction among host genetics, Streptococcus skin colonization, and psoriasis inflammation, offering potential avenues for novel treatment approaches.

Real-world use, perception, satisfaction, and adherence of calcipotriol and betamethasone dipropionate PAD-cream in patients with plaque psoriasis in Spain and Germany: results from a cross-sectional, online survey

Background Psoriasis significantly impacts patients’ quality of life (QoL). Dissatisfaction and non-adherence are major barriers associated with topical treatments. A cream based on the polyaphron dispersion (PAD) Technology containing a fixed-dose of calcipotriol (CAL) and betamethasone dipropionate (BDP) was designed for a patient-friendly psoriasis management. The CAL/BDP PAD-cream demonstrated efficacy, convenience, and safety/tolerability in clinical trials. Objectives This research assesses the real-world use, perception, satisfaction, and adherence of CAL/BDP PAD-cream among plaque psoriasis patients. Methods Between September–November 2023, psoriasis patients from Spain and Germany using or having used CAL/BDP PAD-cream for >2 weeks were recruited via Wefight network to complete a 30-questions online survey. Anonymized results were pooled for descriptive statistical analysis. Results The survey was completed by 129 patients (mean age: 43 years; 66% females; mean psoriasis duration: 12 years). Most patients (93%) were satisfied with CAL/BDP PAD-cream. The 66% reported high adherence (visual analogue scale 80-100) and 91% preferred CAL/BDP PAD-cream to their previous topical(s). Patients highlighted its ease/convenience of application, tolerability, and lack of itching/burning. Conclusions Psoriasis patients treated with CAL/BDP PAD-cream in a real-world setting show high satisfaction, good adherence, and a positive perception of the product, suggesting that favorable outcomes observed in clinical trials translate to real clinical practice.

Efficacy and safety of weekend cyclosporine treatment as maintenance therapy for preventing frequent disease exacerbations in moderate to severe chronic plaque psoriasis patients - A retrospective cohort study.

Background Psoriasis is a chronic, inflammatory, systemic disease with predominant manifestations in the skin and joints impairing patient's quality of life. A proportion of patients have frequent severe disease exacerbations requiring repeated systemic treatments. There is a scarcity of literature evaluating the role of systemic maintenance therapy in psoriasis patients in preventing such frequent disease flares. Objective To evaluate the efficacy and safety of weekend cyclosporine treatment (WCT) as maintenance therapy in moderate to severe chronic plaque psoriasis patients for the prevention of frequent disease exacerbations. Methods In this retrospective cohort study, 22 psoriasis patients with a history of frequent disease exacerbations (≥ 3 in the last 1 year) who were administered WCT (group A) were compared with the same number of matched patients (age and gender) not on WCT or any systemic maintenance therapy (group B). Results Four patients (18.2%) in group A had disease exacerbations which was significantly lower (p = 0.00, Fisher's exact test) as compared to 21 patients (95.5%) in group B during the study period. Also, patients in group A had significantly lower number of overall exacerbations [mean ± SD: 0.23 ± 0.53 vs 2.95 ± 1.43) p = 0.00, Mann-Whitney U test] as compared to group B. Four (9.1%) patients in group A encountered adverse effects (acneiform eruptions - two, mild gingival hyperplasia - one, myalgia - one) as compared to three (acneiform eruptions - two, headache - one) in group B (p = 1.00). Conclusion WCT significantly reduced the number of disease exacerbations and is a safe and effective mode of maintenance therapy in such subset of psoriasis patients.

Real-World Long-Term Effectiveness of Risankizumab Among Patients with Moderate-to-Severe Psoriasis: Analysis from an International Medical Chart Review (RAPID) Study.

Real-world data on the efficacy of risankizumab (RZB) in clinical moderate-to-severe plaque psoriasis (PsO) are limited. The RAPID study assessed real-world clinical and patient-reported outcomes in RZB-treated PsO patients using data collected from dermatologists in Canada, the Czech Republic, Germany, Japan, and Poland. This ongoing, retrospective chart review collected data from medical records of RZB-treated adults with moderate-to-severe PsO (09/2022-06/2023). Eligible patients received RZB, had ≥ 12months of medical records after RZB initiation (index date), and had Psoriasis Area and Severity Index (PASI), Investigator Global Assessment (IGA), or static Physician's Global Assessment (sPGA) scores ≥ 3months before and up to 18months after the index date. The proportion of patients achieving a clear/almost clear PsO (IGA/sPGA = 0/1), PASI ≤ 1, Dermatology Life Quality Index (DLQI) = 0/1, and a 90%/100% improvement from baseline in PASI as well as the mean changes in PASI, DLQI, itch, and skin pain scores at 12 and 18 months were reported for patients with non-missing assessments at baseline and 12months. Most patients (66.4%) were male, 74.0% were biologic naïve, and 73.0% had scalp PsO. Mean baseline IGA/sPGA was 3.7 ± 0.5, with a mean PASI of 23.3 ± 11.8. After 12months, 86.1% of patients reported IGA/sPGA ≤ 1, and 75.7% achieved PASI90; these further increased to 91.1% and 80.5% at 18months. DLQI, itch, and skin pain scores improved over time. These data demonstrated the durable, real-world effectiveness of RZB in patients with moderate-to-severe PsO through continued improvement in disease and symptom severity over 18months, with most of the patients reporting clear/almost clear skin.

Impact of Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, Deucravacitinib, on Psoriasis in Patients with Active Psoriatic Arthritis: Results from a Phase 2 Trial

Introduction: Deucravacitinib (DEUC), an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy. DEUC was superior to apremilast and placebo (PBO) in two phase 3 trials in patients with moderate to severe PsO. DEUC was efficacious on multiple measures of arthritis severity vs PBO in a phase 2 trial in patients with active psoriatic arthritis (PsA) who had ≥1 PsO lesion (≥2 cm). In patients with body surface area (BSA) involvement ≥3% at baseline (80% of patients in this trial), a greater proportion achieved PASI 75 with DEUC (6 mg QD: 42.4%, P=0.01; 12 mg QD: 59.6%, P&lt;0.0001) vs PBO (20.4%) at Week 16. This analysis evaluated the impact of DEUC on PsO in patients with PsA in the phase 2 trial (NCT03881059).&#x0D; Methods: The phase 2 double-blind PsA trial randomized patients (N=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or DEUC 12 mg QD. After Week 16, patients could enroll in an optional, double-blind period until Week 52. DEUC-treated patients achieving minimal disease activity at Week 16 continued DEUC to Week 52. PsO disease activity measurements were assessed.&#x0D; Results: Baseline PsO characteristics were comparable across groups. At Week 16, significant decreases from baseline in mean PASI were observed with DEUC vs PBO in patients with baseline BSA ≥3%-&lt;10% or PASI ≤12 even with very low baseline PASI scores, and also in those with baseline BSA ≥10% and PASI &gt;12. Significant decreases in PASI from baseline were observed with DEUC vs PBO in patients with background csDMARD use (DEUC 6 mg, -4.0 and 12 mg, -4.9 vs PBO, -2.3; both P&lt;0.05) and those without csDMARD use (-3.7 and -4.0 vs -2.5, respectively; both P&lt;0.001). At Week 16, greater proportions of DEUC vs PBO patients achieved PASI ≤1 with baseline BSA ≥3% (DEUC 6 mg: 32.2%; DEUC 12 mg: 44.2%; PBO: 18.5%) and in patients with baseline BSA ≥10% and PASI &gt;12 (23.1%; 28.6%; 0.0%). In patients with baseline BSA ≥3%, decreases in mean PASI at Week 16 were maintained through Week 52 in patients continuing DEUC 6 mg (absolute PASI score, Week 16: 2.39, Week 52: 1.22) and 12 mg (Week 16: 0.64, Week 52: 0.24).&#x0D; Conclusion: DEUC significantly improved PsO in patients with PsA, regardless of baseline PsO severity and background csDMARD use. Improvement was comparable to that observed in the phase 3 POETYK PSO-1 trial.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Bimekizumab Efficacy Through 3 Years in Patients with Moderate to Severe Plaque Psoriasis: Long-term Pooled Analysis from BE BRIGHT

Introduction: A key factor of biologic discontinuation in plaque psoriasis patients is loss of response over time; long-term treatment efficacy is therefore important.1 Here, 3-year efficacy of bimekizumab (BKZ) from a pooled analysis of patients with moderate to severe plaque psoriasis across 3 phase 3 clinical trials and their open-label extension (OLE) is reported.&#x0D; Procedure/study: Data were pooled from the 52-week BE VIVID and 56-week BE SURE and BE READY phase 3 trials, and their common OLE BE BRIGHT.2–5 Included patients received BKZ 320 mg every 4 weeks (Q4W) then switched to Q4W or Q8W maintenance dosing from Week 16 onwards, and entered the OLE; from OLE Week 48 or the next scheduled visit, all patients received BKZ 320 mg Q8W. Proportions of patients achieving ≥90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90), PASI 100, and Dermatology Life Quality Index (DLQI) 0/1 are reported through Year 3 using modified non-responder imputation: patients who discontinued treatment due to lack of efficacy or treatment-related adverse events were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data.&#x0D; Results: 771 patients received BKZ continuously in the feeder studies and entered the OLE. Among these, at Week 16, 90.9%, 65.8%, and 71.5% achieved PASI 90, PASI 100, and DLQI 0/1, respectively. At Year 1, 93.7%, 76.6%, and 83.1% of all BKZ-treated patients achieved PASI 90 (Week 52), PASI 100 (Week 52), and DLQI 0/1 (Week 48/52), respectively. Responses were durable to Year 3 (OLE Week 96): 91.0%, 70.3%, and 82.8% of all BKZ-treated patients achieved PASI 90, PASI 100, and DLQI 0/1, respectively. Similar trends were observed in the subset of patients that received BKZ Q4W/Q8W/Q8W (initial/maintenance/OLE).&#x0D; Conclusion: High and durable clinical and health-related quality of life responses were observed over 3 years of BKZ treatment across 3 phase 3 trials and their OLE.&#x0D; Funding: UCB Pharma.

Blood Monocyte Count Can Predict Early Response to Secukinumab Therapy in Patients With Psoriasis.

Early response to treatment with biologics, defined as Psoriasis Area and Severity Index (PASI) of 2 or less six months after initiation of therapy, seems to be associated with more stable psoriasis and a lower risk of flares and treatment discontinuation. This study aimed to identify markers that can predict early response to treatment with secukinumab in patients with plaque psoriasis. Treatment with secukinumab was initiated in 29 biologic-naive patients with plaque psoriasis (75.9% males). After six months, the patients were stratified as (1) PASI 2 or less responders or (2) PASI greater than 2 responders. Patients who achieved PASI 2 or less six months after initiation of secukinumab therapy already had significantly greater PASI reductions after the first month of therapy compared to those with PASI greater than 2 six months after treatment. Baseline blood monocyte counts significantly correlated with PASI, both before and six months after initiating secukinumab therapy. A lower monocyte count with a cutoff value set at less than 0.69 &times; 103/microL (based on ROC curve analysis) was found in multivariate analysis to be an independent factor for achieving PASI 2 or less six months after initiation of therapy with secukinumab (R2 = 0.7; beta = -0.67; P = 0.03). We showed that baseline monocyte count may be useful for predicting early response to secukinumab therapy in plaque psoriasis patients. Identifying such a marker may help clinicians choose the most appropriate biologics for patients with plaque psoriasis and help avoid the expense of switching from one biologic to another. J Drugs Dermatol. 2024;23(2):74-77.&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.7525.

Study of gut microbiome alterations in plaque psoriasis patients compared to healthy individuals.

Many studies have shown significant alterations in the gut microbiome of patients with psoriasis compared to healthy controls. The primary objective of the current research was to explore the impact of gut microbiome composition on the progression and severity of plaque psoriasis. A total of 20 patients with moderate-to-severe psoriasis and 20 healthy individuals were recruited and provided a stool sample to assess the gut microbiome. After the samples were prepared according to the NGS library preparation workflow, they were sequenced using the Illumina platform and the report was generated that underwent statistical analysis. The microbiome profiles of psoriasis patients exhibited significant differences compared to healthy controls as evidenced by the statistical analysis of various bacterial genera, with the median abundance significantly lower in psoriasis patients compared to healthy controls (p = 0.033). The analysis of the Firmicutes-to-Bacteroidetes ratio, a commonly evaluated marker of dysbiosis, did not reach statistical significance (p = 0.239). However, there was a noticeable trend towards a higher median ratio in psoriasis patients compared to healthy controls. The ratio did not show significant associations with PASI or BSA but trends towards significance with DLQI (B = -12.11, p = 0.095). Overall, the above findings underscore the importance of the gut microbiome in psoriasis and suggest that modulation of specific bacterial genera, especially that with significant differences, could be a potential strategy for therapeutic intervention. Targeting these depleted genera through microbiome-based interventions, such as probiotic supplementation or faecal microbiota transplantation, could potentially help to restore gut homeostasis and alleviate the inflammatory burden in psoriasis.

Reactivation Risk of Latent Tuberculosis or Inactive Hepatitis B Virus Infection and Effectiveness of Ustekinumab in Chinese Plaque Psoriasis Patients: A 28-Week Retrospective, Observational Study.

This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment. This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤1/3 and Physicians' Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28. A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P<0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline. Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.