Introduction: Scalp psoriasis adversely affects patients' lives and is often resistant to treatment; however, it has not been a major focus of a clinical study. This analysis assessed the effect of ...secukinumab on patient-reported outcomes (PRO) of scalp psoriasis.
Methods: A randomized, double-blind, placebo-controlled, multicenter study was conducted in 102 adult patients with moderate-to-severe scalp psoriasis. Patients were randomized 1:1 to secukinumab 300 mg or placebo. Patients rated their scalp-related pain, itching and scaling using a 0-10 numeric rating scale (higher scores indicate greater severity). Scalp dermatitis-related quality of life (QOL) was assessed at baseline and then every 4 weeks using the Scalpdex. Analysis of covariance models examined PRO effect up to 12 weeks.
Results: Baseline scalp pain, itching and scaling mean (SD) values were 3.1 (3.00), 6.7 (2.60) and 7.3 (2.02) and similar for both treatment groups. At week 12, patients treated with secukinumab reported greater reduction in scalp pain (−1.98 vs. 0.61), itching (−4.07 vs. −0.04) and scaling (−5.76 vs. −0.95) as well as greater improvements in Scalpdex total scores (−39.62 vs. −7.91) compared with placebo (all p < .001).
Discussion/Conclusions: Secukinumab in moderate-to-severe scalp psoriasis reduces scalp pain, itching, and scaling and improves patients' QOL.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: Psoriasis can greatly impact patients' lives, influencing what clothing they wear and impairing their sexual functioning.
Objective: To provide a detailed comparison of the impact of ...secukinumab vs. etanercept on enabling patients with psoriasis to have more normal lives with respect to daily activities (DA) (e.g. choosing clothing) and personal relationships (PR) (e.g. sexual functioning).
Methods: Baseline to Week 52 ERASURE and FIXTURE data for secukinumab 300 mg and etanercept were analyzed. Treatment differences in mean scores on the DA and PR subscales and items from the Dermatology Life Quality Index were compared. The proportions of subscale and item responders (score = 0) were compared.
Results: Subjects receiving secukinumab (n = 572) achieved greater mean improvement in DA and items (q3 and q4) than subjects receiving etanercept (n = 326; all p < .01 through Week 52). Subjects receiving secukinumab achieved greater mean improvement in PR and items (q8 and q9) than subjects receiving etanercept (subscale: p < .05 at Weeks 8 and 12). Response rates were significantly higher for secukinumab than for etanercept for DA (all p < .0001) and PR (all p < .05 except Weeks 4 and 36).
Conclusions: Secukinumab 300 mg provides greater improvements and more effective relief from psoriasis impact on DA and PR than etanercept.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background Although griseofulvin is currently considered the primary antifungal agent used to treat tinea capitis in many countries, increasingly higher doses and longer durations of treatment are ...becoming necessary to achieve effective treatment. Alternative antifungal therapies with shorter/simpler treatment regimens may be important to develop for this indication. Objective To compare the efficacy and safety of a new pediatric formulation of terbinafine hydrochloride oral granules with griseofulvin oral suspension in the treatment of tinea capitis. Method Children (4-12 years of age) with clinically diagnosed and potassium hydroxide microscopy–confirmed tinea capitis were randomized in two identical studies (trial 1, trial 2) to once-daily treatment with terbinafine (5-8 mg/kg; n = 1040) or griseofulvin administered per label (10-20 mg/kg; n = 509) for a period of 6 weeks followed by 4 weeks of follow-up. End-of-study complete cure (negative fungal culture and microscopy with Total Signs and Symptoms Score TSSS = 0), and mycologic (negative culture and microscopy) and clinical cure (TSSS = 0) were primary and secondary efficacy variables, respectively. Efficacy analysis was based on pooled data using modified intent-to-treat population (those who received at least one dose of study drug and had positive baseline fungal culture, N = 1286). Safety assessments included monitoring of the frequency and severity of adverse events (AEs). Results Rates of complete cure and mycologic cure were significantly higher for terbinafine than for griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P < .05). A majority (86.7%) of patients received griseofulvin, 10 to 19.9 mg/kg per day; complete cure rate was not found to be higher among patients who received griseofulvin more than 20 mg/kg per day compared with those who received less than 20 mg/kg per day. Complete cure rate was statistically significantly greater for terbinafine compared to griseofulvin in trial 1 (46.23% vs 34.01%) but not in trial 2 (43.99% vs 43.46%). On the basis of pooled data, clinical cure was higher for terbinafine than for griseofulvin, but the difference was not found to be statistically significant ( P = .10). Subgroup analyses revealed that terbinafine was significantly better than griseofulvin for all cure rates—mycologic, clinical, and complete—among patients with Trichophyton tonsurans but not Microsporum canis ( P < .001). For M canis , mycologic and clinical cure rates were significantly better with griseofulvin than with terbinafine ( P < .05). Approximately 50% of patients in each group reported an AE; almost all were mild or moderate in severity. Nasopharyngitis, headache, and pyrexia were most common in both groups. There were no drug-related serious AEs, no deaths, and no significant effects on weight or laboratory parameters, including liver transaminases. Limitations In retrospect, a difference in the distribution of infecting microorganisms between the two trials was a limitation. Stringent adherence to griseofulvin doses recommended by prescribing information but smaller than those used in current clinical practice, and exclusion of adjuvant therapies such as shampoos or topical agents, which are routinely used in practice, are other limitations. Conclusions Data from this largest pediatric trial of terbinafine to date indicate that terbinafine is efficacious and well tolerated in the treatment of tinea capitis. Terbinafine is an effective alternative to griseofulvin against T tonsurans tinea capitis.
Background: Conventional measurements for assessing psoriasis treatment effects capture improvements at fixed, pre-specified timepoints, failing to account for cumulative clinical benefit over time.
...Objective: Explore the innovative concept of "cumulative clinical benefit" by examining the effect of secukinumab over 52 weeks in moderate-to-severe psoriasis patients.
Methods: Cumulative clinical benefit was determined as the area-under-the-curve of the percentage of responders over 52 weeks (AUC
0-52 wks
), using pooled data from two phase III trials for patients receiving secukinumab (300 or 150 mg) or etanercept.
Results: Normalized cumulative benefit with secukinumab 300 mg, secukinumab 150 mg, and etanercept was 74.2%, 63.2%, and 50.5%, respectively, for PASI 75; 58.0%, 42.5%, and 29.5%, respectively, for PASI 90; 32.3%, 18.8%, and 8.7%, respectively, for PASI 100; and 58.3%, 47.9%, and 38.3%, respectively, for DLQI 0/1. 52-week PASI 75 clinical benefit ratios for secukinumab 300 and 150 mg versus etanercept were 1.47 and 1.25, respectively; the ratio of the two secukinumab doses was 1.17, favoring 300 mg.
Limitations: Post hoc analysis.
Conclusion: Cumulative clinical benefit estimated by AUC
0-52 wks
is a novel measure for comparing psoriasis treatments. Secukinumab 300 mg provides greater cumulative clinical benefit than secukinumab 150 mg; both provide greater cumulative benefit than etanercept.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Objectives This research evaluated the psychometric properties of a new Psoriasis Symptom Diary, identified diary responder definitions for use in determining whether a patient has ...experienced clinically meaningful change, and refined diary item content for use in future clinical trials. Methods The Psoriasis Symptom Diary was administered in a phase 2 clinical trial of AIN457 to US adult outpatients (N = 172) with physician-diagnosed moderate to severe chronic plaque-type psoriasis. Participant compliance with daily diary administration and item score variability, reliability, construct and discriminant validity, sensitivity to change, and interpretation were all evaluated. Results Participants completed 94% of scheduled diary assessments across 12 study weeks. Diary items were generally normally distributed, and no floor or ceiling effects were observed. Item reliability (reproducibility) was acceptable (intraclass correlation coefficients > 0.80), with an exception for one item (skin color). At week 12, items significantly related to criterion measures as predicted (Psoriasis Area and Severity Index r = 0.27–0.57; Investigator’s Global Assessment r = 0.25–0.59), with the exception of items that measured skin color and difficulty using hands. Most items generated change scores that were synchronous to changes as measured by the Psoriasis Area and Severity Index, Investigator’s Global Assessment, Dermatology Life Quality Index ( r > 0.37), as well as the Patient Global Impression of Change. Responders experienced a 2- to 3-point and 3- to 5-point change in item scores for minimal and large improvements, respectively. Four items that did not perform well were dropped from the diary. Conclusions The 16-item Psoriasis Symptom Diary demonstrated favorable psychometric properties and is a brief, useful tool for measuring patient-based symptoms and the impact of chronic plaque psoriasis.
Secukinumab is a human monoclonal antibody with demonstrated efficacy for moderate to severe psoriasis; it binds to and neutralizes interleukin (IL)‐17A. The pharmacokinetic (PK) parameters of ...secukinumab were best described by a 2‐compartment model. Only weight was included in the final model, as other covariates did not affect clinical relevance. The estimated serum clearance of secukinumab was 0.19 L/day, with interindividual variability (IIV) of 32% coefficient of variation (CV), and low total volume of distribution (central compartment volume, 3.61 L with IIV of 30% CV; peripheral compartment volume, 2.87 L with IIV of 18% CV). The bioavailability of secukinumab after subcutaneous dosing was approximately 73%, with an absorption rate of 0.18/day with IIV of 35% CV. The PK profile of secukinumab was linear, with no evidence of a dose dependence of clearance. Clearance and volume of secukinumab varied with body weight in an allometric relationship. The time to maximum serum concentration at steady state occurred approximately 6 days after dosing for both secukinumab 300 mg and secukinumab 150 mg. Overall, the PK properties of secukinumab were typical of a 150‐kDa human IgG1 antibody interacting with a soluble target.
Moderate-to-severe scalp psoriasis has not been evaluated in prospective trials of patients without moderate-to-severe body psoriasis.
Evaluate the efficacy and safety of secukinumab in ...moderate-to-severe scalp psoriasis.
In this 24-week, double-blind, phase 3b study, 102 patients were randomized 1:1 to subcutaneous secukinumab 300 mg or placebo at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 20. The primary efficacy variable was 90% improvement of Psoriasis Scalp Severity Index (PSSI 90) score from baseline to week 12.
At week 12, PSSI 90 (secukinumab 300 mg vs placebo, 52.9% vs 2.0%) and Investigator's Global Assessment modified 2011 scalp responses of 0 or 1 (secukinumab 300 mg vs placebo, 56.9% vs 5.9%) were significantly greater with secukinumab 300 mg than placebo (P < .001 for both). In addition, significantly more patients achieved complete clearance of scalp psoriasis at week 12 with secukinumab 300 mg than placebo (35.3% vs 0%; P < .001). The median time to 50% reduction in PSSI score was 3.29 weeks with secukinumab 300 mg. The safety profile of secukinumab was consistent with previous phase 3 studies.
There was no active comparator arm.
Secukinumab is efficacious and well-tolerated for patients with extensive moderate-to-severe scalp psoriasis.
Abstract
Background: To evaluate new psoriasis treatments, clinicians, regulators and pharmaceutical developers require well-accepted, clinically meaningful measures of disease severity. The ...Psoriasis Area and Severity Index (PASI) score is most widely used as a primary endpoint in clinical trials, although it is not routinely used in clinical practice. Objective: Characterize a 5-point Investigator's Global Assessment (IGA) tool and evaluate whether it meets the needs for a valid, clinically meaningful measure. Methods: A 5-point IGA tool was developed with input from regulatory authorities and clinical trial investigators involved with psoriasis drug development and evaluation. Associations between IGA 0/1 responder rates and PASI scores were evaluated using data from two phase 2 studies with the anti-interleukin (IL)-17A monoclonal antibody secukinumab (AIN457) that utilized a similar 6-point IGA. Results: The 5-point IGA has a more stringent definition for a score of 1 ("almost clear") compared with 6-point IGA/Physician's Global Assessment (PGA) tools used in previous trials of other biologics in moderate-to-severe psoriasis. Whereas IGA/PGA 0/1 responder rates for earlier scales are strongly associated with PASI 75, the IGA 0/1 rate for the secukinumab 6-point scale was more robust, demonstrating a strong association with PASI 90, and the results for the 5-point IGA are expected to show the same association. Discussion: The 5-point IGA is a valid measure of disease severity and meets the need for a clinically meaningful measure of success for psoriasis treatment studies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To evaluate the risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) complications, and assess healthcare costs in menopausal women using an estradiol transdermal system versus oral ...estrogen therapy (ET).
Health insurance claims from 60 self-insured US companies from 1999 to 2011 were analyzed. Women at least 50 years of age, newly initiated on transdermal or oral ET, were included. Cohorts were matched 1:1 based on exact factors and propensity score-matching methods. The incidence rate ratios (IRRs) of CVD complications, as well as VTE and other CVD events separately, were assessed through conditional Poisson models. Cohorts were also compared for healthcare costs using linear regression models to assess per-patient per-month cost differences. Confidence intervals (CIs) and P values were determined using a nonparametric method for cost outcomes.
From each cohort, 2,551 users were matched to form the study population. A total of 274 transdermal ET users developed CVD complications compared with 316 women in the oral ET cohort (adjusted IRR 0.81; 95% CI, 0.67-0.99). Transdermal ET users also incurred lower adjusted all-cause and VTE/CVD-related healthcare costs relative to oral ET users (all-cause per-patient per-month cost difference 95% CI = $41 -34; 137, P = 0.342).
This large matched-cohort study based on real-world data suggests that women receiving transdermal ET have significantly lower incidences of CVD events compared with those receiving oral ET, and that they also incur lower healthcare costs.
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