Psoriasis-affected Body Surface Area Research Articles

Long-term Efficacy and Safety of Up to 108 Weeks of Ixekizumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis

About 1% of children and adolescents worldwide are affected by plaque psoriasis. To evaluate the long-term efficacy and safety of ixekizumab for pediatric patients with moderate to severe psoriasis. This multicenter randomized clinical trial (IXORA-PEDS) evaluated pediatric patients with plaque psoriasis. Participants were aged 6 years to younger than 18 years; had moderate to severe psoriasis, which was defined as Psoriasis Area and Severity Index (PASI) of 12 or higher, static Physician's Global Assessment (sPGA) score of 3 or higher, and psoriasis-affected body surface area of 10% or greater at screening and baseline; were candidates for phototherapy or systemic therapy; or had psoriasis that was not adequately controlled by topical therapies. Data analysis, which followed the intention-to-treat principle, was conducted from May to October 2021. Pediatric patients were randomized 2:1 to receive either a weight-based dose of ixekizumab every 4 weeks or placebo. After a 12-week placebo-controlled period, patients entered a 48-week, open-label ixekizumab maintenance period (weeks 12-60), followed by an extension period that lasted through 108 weeks. A substudy evaluated the randomized withdrawal of ixekizumab after week 60. Efficacy outcomes at week 108 included the percentage of patients achieving 75% (PASI 75), 90% (PASI 90), or 100% (PASI 100) improvement from baseline; an sPGA score of 0 or 1 or score of 0; and improvement of 4 points or higher from baseline in the Itch Numeric Rating Scale. Safety outcomes included assessments of adverse events (AEs), including treatment-emergent AEs, serious AEs, and AEs of special interest, as well as improvement from baseline in a range of challenging body areas. Missing data for categorical outcomes were imputed using modified nonresponder imputation. A total of 171 patients (mean [SD] age, 13.5 [3.04] years; 99 female children [57.9%]) were randomized to either ixekizumab (n = 115) or placebo (n = 56). Of 166 patients who entered the maintenance period, 139 (83.7%) completed week 108 of the trial. Primary and gated secondary end points were sustained through week 108, with patients achieving PASI 75 (91.7% [n = 86]), PASI 90 (79.0% [n = 74]), PASI 100 (55.1% [n = 52]), sPGA 0 or 1 (78.3% [n = 74]), and sPGA 0 (52.4% [n = 49]). Fifty-five patients (78.5%) reported an Itch Numeric Rating Scale improvement of 4 points or higher. In patients who received ixekizumab, at week 108, clearance of nail psoriasis was reported in 68.1% (n = 28), clearance of palmoplantar psoriasis was reported in 90.0% (n = 10), clearance of scalp psoriasis was reported in 76.2% (n = 83), and clearance of genital psoriasis was reported in 87.5% (n = 24). There were no new safety findings during weeks 48 to 108 of the trial, including no new cases of inflammatory bowel disease or candida infection. Results of this study showed improvements across patient-reported outcomes and objective measures of complete skin clearance of psoriasis among pediatric patients who received ixekizumab, and these response rates were sustained through week 108 of the trial. Safety of ixekizumab was consistent with previously reported findings in this population and the known safety profile of this treatment. ClinicalTrials.gov Identifier: NCT03073200.

Dermatologists' Perspectives on Defining Moderate Psoriasis: The Canadian Moderate Psoriasis Survey.

Psoriasis is commonly classified as either mild or moderate to severe, without specific parameters to differentiate moderate versus severe disease. This may lead to patients with moderate psoriasis being underrecognized and undertreated. An online survey was conducted to assess Canadian dermatologists’ perspectives on the definition and treatment of psoriasis. Dermatologists included in the survey were regional and national leaders with expertise in psoriasis. Questions were developed based on feedback from a steering committee of Canadian dermatologists. Of 88 dermatologists contacted, 69 responded; 42.0% were in practice for >20 years. Most dermatologists reported using the percentage of psoriasis-affected body surface area (BSA) to describe disease severity (90.8% for moderate and 87.5% for severe psoriasis). The lower and upper median cutoffs for moderate psoriasis were reported as 5.0% and 10.0% for BSA and 7.0 and 11.5 for the Dermatology Life Quality Index. Most dermatologists also consider psoriasis location (eg, palms, scalp, genital area, face) as an important indicator of disease severity. The majority of Canadian dermatologists (87.5%) identified access to treatment as one of the biggest challenges for patients with moderate psoriasis. Most dermatologists estimated that ≤40% of their patients with moderate plaque psoriasis were being treated with traditional oral systemics, targeted oral systemics, or biologics. This is the first survey of Canadian dermatologists on moderate psoriasis. Efforts are needed to implement a clinically useful definition of moderate plaque psoriasis to improve patient care and to raise awareness of the definition among regulatory agencies and reimbursement authorities. J Drugs Dermatol. 2021;20(2):126-132. doi:10.36849/JDD.5531.

SAT0429 SECUKINUMAB IMPROVES CLINICAL AND PATIENT-REPORTED OUTCOMES AT 6 MONTHS AMONG PATIENTS WITH PSORIATIC ARTHRITIS IN THE US-BASED CORRONA PSORIATIC ARTHRITIS/SPONDYLOARTHRITIS (PsA/SpA) REGISTRY

Background:Secukinumab, an interleukin-17 antagonist approved for the treatment of PsA, improves all PsA manifestations in the GRAPPA-OMERACT core domain set.1Few US-based studies have evaluated the real-world effectiveness of secukinumab in patients with PsA.Objectives:To examine clinical and patient-reported outcomes (PROs) in patients with PsA enrolled in the Corrona PsA/SpA registry initiating secukinumab with ≥ 1 follow-up visit.Methods:Included were adult patients with PsA in the Corrona registry who initiated secukinumab after April 1, 2017 and remained on secukinumab at their 6-month (window, 5-8 months) follow-up visit. The primary outcome was achievement of minimal disease activity (MDA) at 6 months among patients not in MDA at secukinumab initiation. MDA was defined as meeting 5 of the 7 following criteria: tender joint count (TJC) ≤ 1, swollen joint count (SJC) ≤ 1, psoriasis affected body surface area (BSA) < 3%, patient assessment of pain on visual analog scale (VAS) ≤ 15, patient global assessment VAS ≤ 20, HAQ-DI ≤ 0.5, and tender entheseal points ≤ 1 using the Leeds Enthesitis Index (LEI). Secondary outcomes included the proportion of patients who achieved resolution (0 sites) of TJC, SJC, enthesitis (using the LEI), and dactylitis among those with ≥ 1 site at initiation and improvement from baseline in clinical outcomes (BSA, nail psoriasis, physician global assessment, TJC, SJC, and DAPSA) and PROs (patient-reported pain, patient global assessment, HAQ-DI, and Work Productivity and Activity Impairment questionnaire) at 6 months. Outcomes were evaluated in the overall population and in potentially recalcitrant patients with failure of or intolerance to ≥ 3 previous biologics to examine if the later line biologic could be adequately effective.Results:A total of 100 patients with PsA who initiated and maintained secukinumab after 6 months were included. The mean (SD) age was 51.6 (11.6) years, 54.3% were male, and 96.8% were white. The mean (SD) symptom and disease duration were 10.8 (9.7) and 7.0 (7.0) years, respectively. Thirty patients (30.0%) initiated secukinumab 150 mg and 70 (70.0%) initiated secukinumab 300 mg. Most (83.0%) were biologic experienced; 17 patients initiated secukinumab as a 1st biologic, 34 as 2nd, 26 as 3rd, and 23 as ≥ 4th. At initiation, 75/90 patients (83.3%) were not in MDA; 26/71 (36.6%) of those with follow-up data available achieved MDA at 6 months (Figure 1). In the overall population, 28 patients (41.2%) with TJC ≥ 1, 24 (44.4%) with SJC ≥ 1, 17 (60.7%) with enthesitis, and 9 (75.0%) with dactylitis at initiation achieved resolution at 6 months (Table 1). Improvement was observed at 6 months in clinical outcomes and PROs in the overall population (Figures 1 and 2) and in patients who initiated secukinumab as a ≥ 4th-line biologic.Table 1.Resolution of Peripheral Arthritis, Enthesitis, and Dactylitis at 6 Months Among Patients With ≥ 1 Site at InitiationSecondary OutcomesInitiation,Mean (SD) [n]6-Month Follow-Up,Resolution (Count = 0), n (%)TJC (1-68)9.0 (9.7) [68]28 (41.2)SJC (1-66)4.7 (4.2) [54]24 (44.4)Enthesitis (1-6)1.9 (1.1) [28]17 (60.7)Dactylitis (1-20)2.1 (1.3) [12]9 (75.0)Conclusion:In the Corrona registry, most secukinumab initiators with PsA were biologic experienced and were not in MDA at time of initiation. Consistent with clinical trials, real-world patients treated with secukinumab achieved MDA as well as improvement in clinical manifestations, PROs, and work productivity.

Feasibility and Utility of the Psoriasis Symptom Inventory (PSI) in Clinical Care Settings: A Study from the International Psoriasis Council.

BackgroundThe Psoriasis Symptom Inventory (PSI) is a patient-reported outcome measure designed to assess psoriasis signs and symptoms.ObjectivesThe aim was to assess the usefulness of the PSI in enhancing patient care in the clinical setting.MethodsEight dermatology clinics in six countries enrolled adults representing the full spectrum of psoriasis severity who regularly received care at the clinic. Patients were administered the eight-item PSI (score range 0–32; higher scores indicate greater severity) while waiting for the physician; the physician conducted a static physician global assessment (sPGA) and estimated psoriasis-affected body surface area (BSA) at the same visit. Physicians completed a brief questionnaire after each patient visit, and were interviewed about the PSI after all patients were seen.ResultsThe clinics enrolled 278 patients; mean [standard deviation (SD)] psoriasis-affected BSA was 7.6% (11.4). Based on BSA, 47.8% had mild psoriasis, 29.1% had moderate psoriasis, and 23.0% had severe psoriasis. Based on sPGA, 18.7% were clear/almost clear, 67.3% were mild/moderate, and 14.0% were severe/very severe. The mean (SD) PSI total score was 12.2 (8.3). Physicians spent a mean (SD) 4.9 (4.8) min discussing PSI findings with their patients (range 0–20 min). Key benefits of PSI discussions included the following: new information regarding symptom location and severity for physicians; prompting of quality-of-life discussions; better understanding of patient treatment priorities; change in treatment regimens to target specific symptoms or areas; and improvement of patient–physician relationship.ConclusionsThe PSI was useful for treated and untreated patients to enhance patient–physician communication, and influenced treatment decisions.Electronic supplementary materialThe online version of this article (10.1007/s40257-019-00458-2) contains supplementary material, which is available to authorized users.

Plasma miR-126 expression correlates with risk and severity of psoriasis and its high level at baseline predicts worse response to Tripterygium wilfordii Hook F in combination with acitretin

BackgroundTreatment of psoriasis is always difficult, which requires intensive scientific research. ObjectiveTripterygium wilfordii Hook F (TwHF) with acitretin(TwHF + acitretin) is normally used in treating psoriasis. This study aimed to investigate the correlation of plasma miR-126 expression with risk and severity of psoriasis, and its predictive value of response to TwHF + acitretin treatment in psoriasis. MethodsMiRNA-126(MiR-126) expression in plasma was analyzed in psoriasis patients at month 0 (M0), M1, M3 and M6 and in health controls (HCs) at enrollment by qPCR. Psoriasis-affected body surface area (BSA) and Psoriasis Area and Severity Index (PASI) score were used to assess severity and treatment response. ResultsPlasma miR-126 levels were decreased in psoriasis patients compared with HCs (P < 0.001), with area under the curve (AUC) of 0.771. MiR-126 expression was negatively correlated with PASI score (P = 0.001), and negatively associated with psoriasis-affected BSA (P = 0.825). At M6, 65.3% and 36.1% patients achieved PASI 50 and 75, respectively. MiR-126 increased at M1, M3 and M6 after TwHF + acitretin treatment when comparing with M0 (all P < 0.001). Meanwhile, miR-126 expression baseline in PASI 50 group declined when comparing with non-PASI 50 group (P < 0.001). Additionally, data revealed that the cause of high miR-126 baseline level was due to unsuccessfully achieving PASI 50 at M6 after TwHF + acitretin treatment (P < 0.001). However, miR-126 baseline expression was not a predictive factor for PASI 75 achievement (P > 0.05). ConclusionPlasma miR-126 expression is negatively correlated with psoriasis risk and severity, and its high baseline level can be used as a biomarker to predict worse clinical response to TwHF + acitretin treatment in psoriasis.

Depression Symptoms Predict Worse Clinical Response to Etanercept Treatment in Psoriasis Patients

Background/Aims: This study aimed to investigate the predicting values of depression and anxiety symptoms for clinical response to etanercept treatment in psoriasis patients. Methods: A total of 85 psoriasis patients who received 6 months of etanercept treatment were consecutively enrolled in this prospective cohort study. The Psoriasis Area and Severity Index (PASI) score was evaluated at month 0 (M0), M1, M3, and M6, and the corresponding PASI 75/90 response at each visit was assessed. Also, anxiety and depression symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS) at M0, M1, M3, and M6. Results: Depression symptoms were observed to correlate with female gender (p = 0.004), longer disease duration (p = 0.018), and higher PASI score (p < 0.001), and anxiety symptoms were seen to be associated with female gender (p = 0.017), larger psoriasis-affected body surface area (p = 0.049), and higher PASI score (p = 0.017) in psoriasis patients. After etanercept treatment, HADS-Depression (HADS-D) and HADS-Anxiety (HADS-A) scores were both decreased at M1, M3, and M6 (all p < 0.001) compared with M0. Most importantly, baseline depressed patients presented with a lower PASI 75 response rate at M3 (p = 0.014) and M6 (p = 0.005), and a reduced PASI 90 response rate at M6 (p = 0.045) compared with baseline non-depressed patients. Furthermore, multivariate logistic regression analyses revealed that depression symptoms at baseline were an independent predictive factor for the lower possibility of both PASI 75 response (p = 0.048) and PASI 90 response (p = 0.048) achievements at M6 in psoriasis patients. However, no correlation of baseline anxiety symptoms with PASI 75/90 responses was observed. Conclusion: Depression symptoms at baseline independently predict a worse clinical response to etanercept treatment in psoriasis patients.

Measurement Properties of the Psoriasis Symptom Inventory Electronic Daily Diary in Patients with Moderate to Severe Plaque Psoriasis.

The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome instrument that measures the severity of psoriasis signs and symptoms. This study evaluated measurement properties of the PSI in patients with moderate to severe plaque psoriasis. This secondary analysis used pooled data from a phase 3 brodalumab clinical trial (AMAGINE-1). Outcome measures included the PSI, Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), psoriasis-affected body surface area, 36-item Short-Form Health Survey version 2, and the Dermatology Life Quality Index (DLQI). The PSI was evaluated for dimensionality, item performance, reliability (internal consistency and test-retest), construct validity, ability to detect change, and agreement between PSI response and response measures based on the PASI, sPGA, and DLQI. Results supported unidimensionality, good item fit, ordered responses, and PSI scoring. The PSI demonstrated reliability: baseline Cronbach's alpha ≥ 0.92 and intraclass correlation coefficients ≥ 0.95. Correlations between PSI total score and DLQI item 1 (r = 0.86), DLQI symptoms and feelings (r = 0.87), and 36-item Short-Form Health Survey version 2 bodily pain (r = -0.61) supported convergent validity. PSI scores differed significantly (P < 0.001) among severity groups based on the PASI (< 12/≥ 12), sPGA (0-1/2-3/4-5), body surface area (< 5%/5%-10%/> 10%), and DLQI (≤ 5/> 5) at weeks 8 and 12. At week 12, the PSI detected significant changes in severity based on PASI responses (< 50/50- < 75/≥ 75) and sPGA (0-1/≥ 2), and showed good agreement (k ≥ 0.66) between PSI response and PASI, sPGA, and DLQI responses. The PSI demonstrated excellent validity, reliability, and ability to detect change in the severity of psoriasis signs and symptoms.

Efficacy and safety of Tripterygium wilfordii hook F versus acitretin in moderate to severe psoriasis vulgaris: a randomized clinical trial.

Background:Few clinical trials have evaluated the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) compared with acitretin in psoriasis. We aimed to compare the efficacy and safety of TwHF compared with acitretin in the treatment of moderate to severe psoriasis vulgaris.Methods:Adults with Psoriasis Area Severity Index (PASI) score ≥ 10 and psoriasis-affected body surface area ≥ 10% were randomized into a TwHF (20 mg, 3 times a day) or acitretin group (30 mg, once a day). The treatment course lasted for 8 weeks. Patients were assessed at baseline and at 2, 4, and 8 weeks. Laboratory tests were performed at baseline, week 4, and week 8. The data were analyzed using paired samples t-test or analysis of variance (ANOVA).Results:A total of 115 patients was enrolled (58 TwHF; 57 acitretin). The median PASI score improved in the TwHF group by 50.4% and in the acitretin group by 42.7%. There was no significant difference in median PASI improvement between two groups at 2, 4, and 8 weeks. There was also no significant difference in PASI 25, PASI 50, PASI 75, and PASI 90 response between the two groups at 2, 4, and 8 weeks. There was a significant increase in the level of aspartate transaminase and triglycerides in the TwHF group (P = 0.026 and P = 0.011, respectively). In the acitretin group, there was a significant increase in the level of alanine transaminase, cholesterol, and high-density lipoprotein (P = 0.030, P < 0.01, and P < 0.01, respectively).Conclusions:There was no significant difference in treatment efficacy between the TwHF and acitretin groups within 8 weeks, but there were fewer treatment-related adverse events in the TwHF group.

OBSERVE-5: Observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results

OBSERVE-5 was a 5-year Food and Drug Administration-mandated surveillance registry of patients with psoriasis. We sought to assess long-term etanercept safety and effectiveness. Patients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events, serious infectious events, events of medical interest, psoriasis-affected body surface area, physician global assessment score, and Dermatology Life Quality Index score. Safety outcomes were assessed relative to data from the MarketScan database. For 2510 patients, 5-year cumulative incidence was 22.2% (95% confidence interval [CI] 20.3%-24.2%) for serious adverse events; 6.5% (95% CI 5.4%-7.7%) for serious infectious events; 3.2% (95% CI 2.3%-4.1%) for malignancies excluding nonmelanoma skin cancer; 3.6% (95% CI 2.7%-4.5%) for nonmelanoma skin cancer; 2.8% (95% CI 2.0%-3.6%) for coronary artery disease; 0.7% (95% CI 0.3%-1.2%) for psoriasis worsening; 0.2% (95% CI 0.0%-0.4%) for central nervous system demyelinating disorder; 0.1% (95% CI 0.0%-0.3%) for lymphoma and for tuberculosis; and 0.1% (95% CI 0.0%-0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, nonmelanoma skin cancer, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years. No internal comparator group was included; rare events may not have been detected. No new safety signals were observed with long-term, real-world etanercept use.

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.