Improvement In Psoriasis Area And Severity Index Score Research Articles

Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis

New, effective, and well-tolerated oral therapies are needed for treating psoriasis. Zasocitinib, a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is a potential new oral treatment for this disease. To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis. This phase 2b, randomized, double-blind, placebo-controlled, multiple-dose randomized clinical trial was conducted from August 11, 2021, to September 12, 2022, at 47 centers in the US and 8 in Canada. The study included a 12-week treatment period and a 4-week follow-up period. Key eligibility criteria for participants included age 18 to 70 years; a Psoriasis Area and Severity Index (PASI) score of 12 or greater; a Physician's Global Assessment score of 3 or greater; and a body surface area covered by plaque psoriasis of 10% or greater. Of 287 patients randomized, 259 (90.2%) received at least 1 dose of study treatment. Patients were randomly assigned (1:1:1:1:1) to receive zasocitinib at 2, 5, 15, or 30 mg or placebo orally, once daily, for 12 weeks. The primary efficacy end point was the proportion of patients achieving 75% or greater improvement in PASI score (PASI 75) at week 12. Secondary efficacy end points included PASI 90 and 100 responses. Safety was also assessed. In total, 259 patients were randomized and received treatment (mean [SD] age, 47 [13] years; 82 women [32%]). At week 12, PASI 75 was achieved for 9 (18%), 23 (44%), 36 (68%), and 35 (67%) patients receiving zasocitinib at 2, 5, 15, and 30 mg, respectively, and 3 patients (6%) receiving placebo. PASI 90 responses were consistent with PASI 75. PASI 100 demonstrated a dose response at all doses, with 17 patients (33%) achieving PASI 100 with zasocitinib, 30 mg. Treatment-emergent adverse events occurred for 23 patients (44%) receiving placebo and 28 (53%) to 31 (62%) patients receiving the 4 different doses of zasocitinib, with no dose dependency and no clinically meaningful longitudinal differences in laboratory parameters. This randomized clinical trial found that potent and selective inhibition of TYK2 with zasocitinib at oral doses of 5 mg or more once daily resulted in greater skin clearance than placebo over 12 weeks. ClinicalTrials.gov Identifier: NCT04999839.

Employing zero-inflated beta distribution in an exposure-response analysis of TYK2/JAK1 inhibitor brepocitinib in patients with plaque psoriasis.

Brepocitinib is an oral selective dual TYK2/JAK1 inhibitor and based on its cytokine inhibition profile is expected to provide therapeutic benefit in the treatment of plaque psoriasis. Efficacy data from a completed Phase 2a study in patients with moderate-to-severe plaque psoriasis were utilized to develop a population exposure-response model that can be employed to inform dose selection decisions for further clinical development. A modeling approach that employs the zero-inflated beta distribution was used to account for the bounded nature and distributional characteristics of the Psoriasis Area and Severity Index (PASI) score data. The developed exposure-response model provided an adequate description of the observed PASI scores across all the treatment arms tested and across both the induction and maintenance dosing periods of the study. In addition, the developed model exhibited a good predictive capacity with regard to the derived responder metrics (e.g., 75%/90%/100% improvement in PASI score [PASI75/90/100]). Clinical trial simulations indicated that the induction/maintenance dosing paradigm explored in this study does not offer any advantages from an efficacy perspective and that doses of 10, 30, and 60mg once-daily may be suitable candidates for clinical evaluation in subsequent Phase 2b studies.

CYSLTR1 antagonist inhibits Th17 cell differentiation by regulating the NF-κB signaling for the treatment of psoriasis.

Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast in vitro to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling in vitro. CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.

Guselkumab demonstrates long-term efficacy and maintenance of treatment response postwithdrawal in systemic treatment-naïve patients and nonresponders to fumaric acid esters: results from parts II and III of a randomized active-comparator-controlled phase IIIb trial(POLARIS).

The anti-interleukin-23 antibody guselkumab (GUS) demonstrated favourable week 24 efficacy and safety over fumaric acid esters (FAE) in systemic treatment-naïve patients with moderate-to-severe plaque psoriasis (study part I). To compare, in study part II, the sustainability of treatment responses (weeks 24-32) in GUS- and FAE-treated patients and treatment responses (weeks 32-56) in patients treated with GUS and FAE and in FAE nonresponders switching to GUS; and, in part III, to investigate the maintenance of response through week 100 in patients withdrawn from GUS at week 56. At week 0, systemic treatment-naïve patients were randomized 1 : 1 to GUS or FAE as per label. At week 32, patients with a Psoriasis Area and Severity Index (PASI) 75 (≥ 75% improvement in PASI score) response (r) continued assigned treatment (GUSr-GUS; FAEr-FAE), whereas nonresponders (nr) received GUS (FAEnr-GUS; GUSnr-GUS). GUS-treated patients with a week 56 PASI 90 response (≥ 90% improvement in PASI score) were withdrawn (w) and followed until loss of response or week 100. At week 32, 98% (n = 54/55) of GUS- and 41% (n = 14/34) of FAE-treated patients were PASI 75 responders. At week 56, 91%, 50% and 80% of GUSr-GUS, FAEr-FAE and FAEnr-GUS patients, respectively, achieved a PASI 90 response; 72%, 29% and 45%, respectively, achieved a Dermatology Life Quality Index score of 0/1. At week 100, 44 weeks postwithdrawal, 47% (n = 17/36) and 25% (n = 3/12) of GUS-GUSw and FAE-GUSw patients, respectively, maintained a PASI score ≤ 5. Overall, the adverse event and discontinuation rates were lower for GUS than FAE. In these exploratory analyses, GUS, as a first-line systemic treatment or second-line systemic treatment in FAE nonresponders, was associated with long-term clinical efficacy up to week 100, including a withdrawal period.

Quality of Life Benefit and Clinical Predictors of Complete Skin Clearance in Psoriasis: A Multicenter, Prospective, Real-World Study

Background: Newer biologics, such as interleukin (IL)-17 inhibitors, make it possible to achieve complete skin clearance (CSC) in patients with moderate-to-severe psoriasis. However, the clinical meaningfulness and predictive factors of CSC in daily practice have not yet been fully investigated. Objective: The study was conducted to, first, assess the impact of CSC on quality of life (QoL) improvements compared with treatment responses without clearance and, second, identify clinical parameters as predictors of CSC response in psoriasis patients treated with ixekizumab. Methods: Patients attending 26 dermatology centers across China were recruited into this real-world setting between August 2020 and May 2022. Prospective cohort study in which response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI). The absolute DLQI score and DLQI (0) response at week 12 were compared between groups achieving various levels of skin clearance. A stepwise logistic regression analysis was applied to identify which baseline clinical characteristics were predictive factors for CSC. Results: After 12 weeks of treatment, 226 of 511 (44.2%) patients achieved CSC, defined as 100% improvement in PASI score (PASI-100). A significantly higher proportion of patients with CSC versus almost clear skin (PASI 90-99) achieved DLQI score of 0, corresponding to the experience of no impairment on QoL (54.4% vs. 37.7%, p = 0.001). Females patients were more likely than males to achieve CSC response (odds ratio [OR] = 1.83; 95% confidence interval [CI]: 1.24–2.70), while previous biologic treatment (OR = 0.43; 95% CI: 0.24–0.81) and joint affected (OR = 0.61; 95% CI: 0.42–0.89) were significantly associated with less CSC response. Conclusions: This study highlights the fact that clinical parameters are important in determining CSC response in psoriasis. In daily practice, achieving CSC represents a clinically meaningful treatment goal, especially from the patient perspective.

Hsa_circ_0056856 in the serum serves as a potential novel biomarker for disease activity in psoriasis.

hsa_circ_0056856 in the serum serves as a potential novel biomarker for disease activity in psoriasis.

Certolizumab for the treatment of psoriasis and psoriatic arthritis: a real‐world multicentre Italian study

Certolizumab, a pegylated tumour necrosis factor-α inhibitor, reduced disease activity in randomized trials of patients with psoriasis and psoriatic arthritis. Real-life data are missing. To confirm the effectiveness and safety of certolizumab in patients with psoriasis and psoriatic arthritis in routine clinical practice. In this retrospective study involving 11 Italian sites, patients with psoriasis and psoriatic arthritis received subcutaneous certolizumab (400mg loading dose at 0, 2 and 4weeks, followed by 200mg every 2weeks) for up to 52weeks. Primary outcomes included mean change from baseline in Psoriasis Area and Severity Index (PASI) and modified Nail Psoriasis Severity Index (mNAPSI) scores, and the proportion of patients achieving a 75%, 90% or 100% reduction in PASI score. Other endpoints included Disease Activity Score computed on 44 joints correlated with the erythrocyte sedimentation rate during the first hour (DAS44-ESR), Tender Joint Count (TJC), Swollen Joint Count (SJC), pain [visual analogue scale (VAS) score], inflammatory markers and quality of life (QOL). In the study were enrolled 153 patients (mean age: 55years). Certolizumab reduced the mean PASI score from baseline by 4.45, 6.30 and 7.58 at weeks 12, 24 and 52, respectively (P<0.001 for all). At weeks 24 and 52, 69.6% and 83.3% of patients had a PASI score ≤3. DAS44-ESR, TJC, SJC and mNAPSI scores, and pain VAS were also all significantly improved from baseline at each time point. C-reactive protein levels decreased during treatment, being significant at week 24. On multivariate analysis, psoriasis duration, baseline PASI, mNAPSI and pain VAS scores were found to be predictive of the improvement in PASI score at week 12. Certolizumab displayed also in the real-life encouraging results in both psoriasis and psoriatic arthritis patients.

Cupping for psoriasis vulgaris: A protocol of systematic review and meta-analysis.

Background:Psoriasis vulgaris (PV) is a chronic, immune-mediated dermatological disease that significantly affects the patient's health and quality of life. At present, cupping has been widely used in the treatment of psoriasis. However, the effectiveness and safety of cupping in patients with PV are still controversial. Therefore, this review aims to evaluate the efficacy and safety of cupping therapy on PV.Methods:The following databases will be searched from their inceptions to April 2020 with a language limitation of English and Chinese: Pubmed, Medline, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Databas, China National Knowledge Infrastructure Database, Wanfang database and Chinese Scientific Journal Database. The reference lists of eligible studies and other resources will also be searched. Two researchers will independently perform the selection of studies, data extraction, and data analysis. A fixed or random-effect model will be applied to synthesize data depend on the heterogeneity test. The primary outcome is the proportion of patients achieving at least a 60% improvement in psoriasis area and severity index (PASI) score from baseline (PASI 60). Secondary outcomes include the proportion of patients achieving at least a 90% improvement in PASI score from baseline (PASI 90), the mean change of PASI and dermatology life quality index score, the itching index, adverse events, and recurrence rate. RevMan V.5.3 software will be used for meta-analysis.Results:The study will provide a high-quality evidence-based review of cupping for PV.Conclusions:The study will be conducted to evaluate the efficacy and safety of cupping in the treatment of PV and supposed to provide clear evidence for the clinical application of cupping therapy.Ethics and dissemination:As the study is a protocol of systematic review and meta-analysis that does not involve individual data, ethical approval will not be required. The results will be published in a peer-reviewed journal.OSF Registration number:DOI 10.17605/OSF.IO/KV4CJ

Switching Biologics in the Treatment of Psoriasis: A Multicenter Experience

Background/Objective: The purpose of our study was to provide evidence on the treatment choices, reasons, and results of switching between biologic agents in treating patients with psoriasis. Methods: We conducted a retrospective database search of six tertiary referral centers for pso­riasis patients between January 2007 and May 2019. We analyzed patient and treatment characteristics of all patients in the registry. Results: We enrolled 427 psoriatic patients treated with biologics, and 145 (34%) required a switch to another biologic. The reasons for discontinuing the first biologic agent were inefficacy (n = 106, 62.4%), adverse events (n = 28, 16.5%), and others (n = 36, 21.2%). At week 12, there was a 67.7% reduction in the Psoriasis Area and Severity Index (PASI) score of patients treated with their first biologic, and 51.4% reduction for the second. A drug survival analysis showed no statistically significant difference between the drug survival of first-line biologic agents, but ustekinumab had the highest survival rate among second-line biologics (log-rank p = 0.010). Multivariate analyses for overall drug discontinuation showed that the occurrence of psoriatic arthritis (OR: 1.883, 95% CI: 1.274–2.782, p = 0.001), nail involvement (OR: 2.334, 95% CI: 1.534–3.552, p < 0.001), and use of concomitant treatment (OR: 2.303, 95% CI: 1.403 –3.780, p = 0.001) are predictors for discontinuation. Conclusion: Discontinuation of treatment was most commonly due to inefficacy. Patients who switched to a different biologic agent showed a similar improvement in PASI scores compared to biologic-naive patients. Switching to a second biologic therapy due to inefficacy or adverse events caused by the first one may improve psoriasis.

Rapid Response of Biologic Treatments of Moderate-to-Severe Plaque Psoriasis: A Comprehensive Investigation Using Bayesian and Frequentist Network Meta-analyses.

IntroductionRapid improvement of psoriasis is valued by patients and should be considered to be an important factor in treatment selection. We investigated Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) response rates within the first 12 weeks of treatment to compare the rapid response of 11 biologic therapies for moderate-to-severe psoriasis using Bayesian and Frequentist network meta-analyses (NMA).MethodsA systematic literature review was conducted to identify phase 3, double-blind, randomized, controlled trials for adult patients with moderate-to-severe psoriasis treated with interleukin (IL)-17 (brodalumab, ixekizumab, secukinumab), IL-12/-23 (ustekinumab), IL-23 (guselkumab, risankizumab, tildrakizumab), or tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab). Outcome measures extracted from 32 publications were ≥ 75, ≥ 90, or 100% improvement in PASI score (PASI 75, PASI 90, or PASI 100, respectively) at weeks 2, 4, 8, and 12 and DLQI (0,1), where score (0,1) indicates no effect on patient's life, at week 12. Bayesian NMA (BNMA) used fixed-treatment effect and random-baseline effect, normal independent models. Frequentist NMA (fNMA) was conducted as sensitivity analyses to test the robustness of the findings.ResultsBased on BNMA and fNMA, brodalumab and ixekizumab showed the most rapid treatment effects on PASI 75 at weeks 2, 4, and 8 and on PASI 90 and PASI 100 at weeks 2, 4, 8, and 12; ixekizumab overlapped with risankizumab on PASI 75 at week 12. Brodalumab, ixekizumab, and secukinumab yielded higher DLQI (0,1) gains at week 12 compared to all of the other biologics studied. Additional measures of quality of life were not assessed in this report.ConclusionsIxekizumab and brodalumab provide the most rapid response and earliest clinical benefit at week 2 among all of the biologics studied, including other biologic treatments such as secukinumab, ustekinumab, guselkumab, adalimumab, and etanercept. BNMA and fNMA results showed similar relative effect estimates and treatment rankings.FundingEli Lilly and Company.Electronic supplementary materialThe online version of this article (10.1007/s13555-019-00337-y) contains supplementary material, which is available to authorized users.

Whether Fire-needle Therapy Benefits Plaque Psoriasis: A Multicenter, Randomized, and Controlled Trial.

To observe the clinical effectiveness and safety of fire-needle therapy, an external approach of Chinese medicine in treating plaque psoriasis. This study was a two-parallel-arm randomized controlled trial. A total of 151 participants with plaque psoriasis were randomly assigned to the fire-needle therapy group (treatment group, 76 cases) or the control group (75 cases) at a 1:1 allocation ratio using SAS software. All participants received Oral Huoxue Jiedu Decoction (, HXJDD) and applied externally vaseline cream twice a day. Participants in the treatment group received fire-needle therapy once weekly for 4 weeks plus HXJDD and vaseline cream applied the same as the control group. The primary outcome measure was Psoriasis Area and Severity Index (PASI) score, and the secondary outcomes were Dermatology Life Quality Index (DLQL), and Hamilton Anxiety Rating Scale (HAMA), as well as Chinese medicine (CM) syndrome score and photos of target lesions. The indices were evaluated before and after treatment. Sixty-eight patients in each group completed the study. The treatment group has not yet achieved significant improvement in PASI score (P>0.05) compared to the control group. However, significant differences were found between the two groups in relieving CM syndrome (P<0.05) and improving quality of life (P<0.05). Fire-needle appears to be safe and may have benefit for psoriasis, the short-term treatment and small sample size limit the conclusions of this study. Further rigorous randomized controlled trials with longer treatment are recommended.

Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator–controlled VOYAGE 2 trial

Phase II data suggested that guselkumab, an anti-interleukin-23 monoclonal antibody, was efficacious in psoriasis. We sought to assess efficacy and safety of guselkumab in moderate to severe psoriasis versus placebo and adalimumab, including interrupted treatment and switching adalimumab nonresponders to guselkumab. Patients were randomized to guselkumab 100mg (weeks 0 and 4, then every 8weeks; n=496); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20; n=248); or adalimumab (80mg week 0, then 40mgweek 1, and every 2weeks through week 23; n=248). At week 28, guselkumab 90% or greater improvement in Psoriasis Area and Severity Index (PASI) score from baseline (PASI 90) responders were rerandomizedto guselkumab or placebo with guselkumab after loss of response. Placebo→guselkumab responders and adalimumab responders received placebo, then guselkumab after loss of response. Nonresponders received guselkumab. At week 16, more patients receiving guselkumab achieved an Investigator Global Assessment (IGA) score 0/1 (cleared/minimal) (84.1% vs 8.5%) and PASI 90 (70.0% vs 2.4%) versus placebo (coprimary end points).Guselkumab was superior to adalimumab at week 16 (IGA score 0/1, 75% or greater improvement in PASI score from baseline, and PASI 90) and week 24 (IGA score 0/1 and 0, PASI 90, 100% improvement in PASI score from baseline) (P<.001). From weeks 28 to 48, better persistence of response was observed in guselkumab maintenance versus withdrawal groups(P<.001). Of adalimumab nonresponders who switched to guselkumab, 66.1% achieved PASI 90 at week 48. Guselkumab improved patient-reported outcomes. Adverse events were comparable among groups. One-year follow-up limits retreatment data. Guselkumab is a highly effective, well-tolerated, maintenance therapy, including in adalimumab nonresponders.

Clear or almost clear skin improves the quality of life in patients with moderate-to-severe psoriasis: a systematic review and meta-analysis.

Psoriasis Area and Severity Index (PASI) 75 response is currently considered the gold standard for assessing treatment efficacy in moderate-to-severe psoriatic patients. PASI 90 response denotes better clinical improvement compared to PASI 75. Very few studies have assessed if a greater PASI clinical response is associated with greater improvements in Dermatology Life Quality Index (DLQI). A systematic review and meta-analysis was performed to assess the association between PASI response and DLQI. The study was conducted to assess whether greater improvement in PASI scores from PASI 75-89 to PASI 90 is associated with greater Quality of life (QoL) improvements, specifically DLQI scores. Systematic searches were conducted in MEDLINE, EMBASE and Cochrane Library to identify studies evaluating biologic interventions in adult moderate-to-severe psoriasis patients reporting PASI response and their corresponding DLQI change from baseline score. The quality of evidence was assessed through Jadad score for randomized controlled trials and Downs and Black's checklist for observational studies. Meta-analysis estimated change from baseline in DLQI for PASI 75-89 responders to be 78% (95% credible intervals [CrI]: 75-82%) and for PASI 90 responders to be 90% (95% CrI: 88-93%). This implies 12% greater improvement in DLQI score for PASI 90 responders compared with PASI 75-89 responders. In addition, the meta-analysis also showed a statistically significant difference in DLQI score of 0/1 between PASI 75-89 and PASI 90 responders (45% [95% Crl]; 41.0-50.0% and 73% [95% Crl]; 70.0-76.0%), respectively, Bayesian P < 0.0001). In conclusion, substantial improvement in clinical efficacy is associated with improved QoL in patients with moderate-to-severe psoriasis suggesting that PASI 90 responders (clear or almost clear skin) could achieve a superior QoL compared to PASI 75-89 responders.

DLQI as a major criterion for introduction of systemic agents in patients with mild psoriasis.

Psoriasis is a skin inflammatory chronic disease with negative physical, psychological and social repercussions for those affected. However, patients suffering from mild disease also complain about negative impact on their quality of life, making it difficult for physicians to choose the best treatment strategy. Understanding the impact of systemic treatments on Quality of Life (QoL) in patients with mild psoriasis in daily practice. This is a monocentric retrospective study analysing patients affected by mild psoriasis [Psoriasis Area and Severity Index (PASI)≤6]. Patients were divided into two groups, depending on the treatment decision taken by the physicians: patients who received local and/or UV light therapies and patients who were treated with systemic therapies as a first choice. PASI and Dermatology Life Quality Index (DLQI) scores were measured at each visit. Patients who received systemic therapies as a first choice reported higher QoL impairment, mainly due to psoriasis lesions localized on visible areas. During Follow-up, this group showed better improvement of PASI score and DLQI compared to patients receiving local and/or UV light treatment. Our findings highlight the potential benefit of using systemic therapies in patients with mild psoriasis and high QoL impairment. This study will help physicians to make the right therapeutic decision in patients suffering from mild psoriasis.

Safety and efficacy of kunzea oil-containing formulations for the management ofpsoriasis: a randomized, controlled trial.

Anecdotally, topical kunzea oil has been used to treat various skin conditions, including psoriasis and eczema, with good results. This study compared the clinical efficacy of kunzea oil (20%)-containing formulations in mild to moderate psoriasis. A randomized, comparative, double-blind, 8-week study was undertaken. Thirty patients (age range: 25-74years and mean±SD: 52·8±13·6years) with mild to moderate psoriasis (affecting at least 10% of one or more body regions: arms, head, legs and trunk) randomly received ointment and/or scalp lotion containing 20% kunzea oil (test group) or control medications not containing kunzea oil (control group). Formulations in both treatment arms also contained 5% liquor carbonis detergens (LCD) and 3% salicylic acid. The clinical responses to the test and control formulations were evaluated using the Psoriasis Area and Severity Index (PASI). After 8weeks of treatment, both test and control groups demonstrated a significant (P<0·05) improvement in PASI scores. Subjects in the test group had a decrease in mean±SD PASI score from 12·7±7·9 to 6·7±7·2, whereas the control group showed a decrease in PASI score from 8·1±4·6 to 3·5±4·7. Comparative efficacy analysis between the test and control groups did not reveal any significant difference (P>0·05). The inclusion of kunzea oil made no difference to the efficacy of topical formulations containing LCD and salicylic acid for the treatment of psoriasis.

Guselkumab (an IL-23–specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis

IL-23 expression is increased in psoriatic lesions and might regulate TH17 T-cell counts in patients with psoriasis. We sought to test a novel IL-23-specific therapeutic agent for the treatment of psoriasis. In this randomized, double-blind, placebo-controlled study the safety, tolerability, and clinical response of guselkumab, an anti-IL-23-specific mAb, were evaluated in patients with moderate-to-severe plaque psoriasis. A total of 24 patients were randomized to receive a single dose of placebo or 10, 30, 100, or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis Area and Severity Index (PASI). Additionally, histologic analysis and gene expression in skin biopsy specimens from guselkumab-treated patients were compared with those from placebo-treated patients. At week 12, 50% (10 mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients, respectively, achieved a 75% improvement in PASI scores from baseline compared with 0% of placebo-treated patients. Improvements in PASI scores were generally maintained through week 24 in all guselkumab-treated patients. The proportion of patients experiencing an adverse event was comparable between the combined guselkumab (13/20 [65.0%]) and placebo (2/4 [50.0%]) groups through week 24. Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases in epidermal thickness and T-cell and dendritic cell expression in guselkumab-treated patients compared with values seen in placebo-treated patients. At week 12, significant reductions in psoriasis gene expression and serum IL-17A levels were observed in guselkumab-treated patients. IL-23 inhibition with a single dose of guselkumab results in clinical responses in patients with moderate-to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising therapy for psoriasis.

Early clinical response as a predictor of subsequent response to ixekizumab treatment: results from a phase II study of patients with moderate-to-severe plaque psoriasis

Early identification of responsiveness to biologic treatments in psoriasis has significant clinical and economic implications. To evaluate whether early clinical improvements in Psoriasis Area and Severity Index (PASI) scores could predict subsequent clinical responses in patients treated with ixekizumab, an anti-interleukin-17 monoclonal antibody. This post hoc analysis was derived from a phase II study in patients with moderate-to-severe plaque psoriasis (n = 114) who received multiple doses of ixekizumab 10, 25, 75 or 150 mg subcutaneously over 20 weeks. PASI score improvements from baseline to weeks 2, 4 and 6 were evaluated to determine the optimal threshold for predicting subsequent PASI responses at week 12. Early clinical improvement in disease symptoms at weeks 4 and 6 was predictive of ≥ 75% improvement in PASI score (PASI 75) at week 12 with ≥ 90% predictability. A 40-50% improvement in PASI (PASI 40 to PASI 50) from baseline to weeks 4 and 6 was the optimum range for predicting PASI 75 response at week 12. For all doses combined, achieving PASI 40 at week 4 or week 6 was associated with high negative predictive values (NPVs) (80% and 95%, respectively) and positive predictive values (PPVs) (89% and 84%, respectively). For all doses combined, achieving PASI 50 at week 4 or week 6 was associated with NPVs of 71% and 89% and PPVs of 94% and 89%, respectively. Sensitivity analysis with the high-dose group (75 and 150 mg) results confirmed these findings. Early clinical responses (and nonresponse) may help predict later clinical responses in patients treated with ixekizumab.

A randomized study to evaluate the efficacy and safety of adding topical therapy to etanercept in patients with moderate to severe plaque psoriasis

Few clinical trials have evaluated the combination of topical corticosteroids plus systemic therapies for psoriasis. We sought to evaluate efficacy and safety of etanercept plus topical clobetasol propionate (CP) foam versus etanercept monotherapy for treatment of moderate to severe plaque psoriasis. Adults with Psoriasis Area and Severity Index (PASI) score greater than or equal to 10 and psoriasis-affected body surface area greater than or equal to 10% were randomized to etanercept with CP as needed to clear (2 up-to-2-week courses, weeks 11-12 and 23-24) or etanercept alone (each arm at 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks). A total of 592 patients enrolled (295 etanercept + CP arm; 297 etanercept arm). At week 12, significant differences were observed for response of 75% improvement in PASI score (primary end point, 65.2% vs 48.3% in the etanercept + CP vs etanercept arms, respectively; P < .001), response of 90% improvement in PASI score (29.7% vs 19.4%; P = .009), percentage PASI score improvement (76.5% vs 68.2%; P < .001), static physician global assessment of clear/almost clear (63.1% vs 47.3%; P < .001), and patient satisfaction with treatment (P = .006). Response of 75% improvement in PASI score and static physician global assessment of clear/almost clear were not significantly different between arms at week 24. Patient satisfaction with treatment (P = .001) and percentage improvement in PASI score (P = .031) were also greater in the etanercept + CP arm compared with etanercept only at week 24. Comparable numbers of adverse events occurred in each arm. No placebo for CP foam was provided in the etanercept arm. Addition of CP to etanercept yielded increased efficacy compared with etanercept alone at week 12 without an increase in treatment-related adverse events.

Association of Psoriasis Severity with Serum Prolactin, Thyroid Hormones, and Cortisol before and after Treatment

Background. Prolactin (PRL) level is proposed to be associated with the severity of psoriasis although the previous studies reported different results. Objective. To find the association between PRL levels and severity of psoriasis before and after treatment. In addition, we aimed to find a difference in prolactin, thyroid stimulating hormone (TSH), thyroid hormones (T3 and T4), and cortisol levels between patients with psoriasis and normal controls. Methods. First, the levels of hormones were measured in 30 patients with psoriasis and 30 matched controls. The severity was assessed by psoriasis area and severity index (PASI). Then, patients were treated, and PASI was assessed every week until achieving PASI-75 response. At this time, the hormones were measured again and compared to the baseline. Results. No statistical significant difference was observed in the mean PRL, T3, T4, TSH, and cortisol levels between cases and controls. Comparing to the baseline, a significant decrease in PRL levels and a significant increase in T3 and serum cortisol levels were observed after treatment (P < 0.05), while the changes in other hormones were not significant. Conclusion. After treatment, PRL significantly decreased, and T3 and cortisol levels significantly increased. No correlation between hormone levels and improvement of PASI score existed.

Atorvastatin for the Treatment of Plaque‐Type Psoriasis

To explore the efficacy and safety of oral atorvastatin for the treatment of plaque-type psoriasis. Prospective, randomized, double-blind, placebo-controlled study. University-affiliated psoriasis outpatient clinic in Iran. Forty-two patients aged 16-60 years with a diagnosis of acute or chronic plaque-type psoriasis with body surface area (BSA) involvement of greater than 10% were enrolled; 40 completed the study. Intervention. Oral atorvastatin 40 mg/day (20 patients) or placebo (20 patients) was administered for 12 weeks; patients' topical therapies with emollients, keratolytics, and/or class V corticosteroids were continued during the study period. The Psoriasis Area and Severity Index (PASI) and percentage BSA involvement were used to assess the efficacy of therapy. Mean ± SD baseline PASI scores were 7.42 ± 1.90 and 6.92 ± 1.76 in the atorvastatin and placebo groups, respectively. The primary outcomes were the degree of change in PASI scores and percentage BSA involvement from baseline to week 12. Significant improvement in psoriasis lesions was observed in both the atorvastatin and placebo groups (p<0.001 for both groups). A 75% improvement in PASI score (PASI 75) was achieved in 8 patients (40%) in the atorvastatin group and 7 patients (35%) in the placebo group. However, no statistically significant differences were noted between the two treatment groups in mean PASI score, percentage BSA involvement, and PASI 75. In terms of adverse effects, atorvastatin was well tolerated. Oral atorvastatin 40 mg/day was not associated with therapeutic benefit when given to patients with baseline PASI scores less than 12 who were also treated with standard topical therapies. Additional trials are needed to elucidate the place of statins for the treatment of psoriasis. A larger follow-up study, as well as testing atorvastatin in patients with more intensive disease characterized by high PASI scores, is needed. Studies using higher atorvastatin doses or dose-ranging studies should also be performed.