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Thomas M Siler,1 Craig F LaForce,2 Farid Kianifard,3 James Williams,3 Selwyn Spangenthal4 1Midwest Chest Consultants, St Charles, MO, USA; 2North Carolina Clinical Research, Raleigh, NC, USA; 3Novartis Pharmaceuticals, East Hanover, NJ, USA; 4Charlotte Lung and Health Center, Charlotte, NC, USA Background: Indacaterol 75 µg once daily is a long-acting β2 agonist approved for maintenance bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate patients' perception of onset of effect with a single dose. Methods: In this double-blind, crossover, Phase IV study, 40 patients were randomized to receive a single dose of indacaterol 75 µg or placebo via a dry powder inhaler device. The primary variable was time until patient’s perception of onset of effect, using a simple self-administered (nonvalidated) questionnaire that patients answered at nine protocol-specified time points. Exploratory variables included change in forced expiratory volume in 1 second (FEV1) and change in percent predicted FEV1 from predose to postdose (determined 60–75 minutes postdose). Results: The least-squares mean time to patient’s perception of onset of effect was 25.4 minutes and 23.9 minutes for indacaterol and placebo, respectively. There was no significant effect for treatment, period, or sequence on the time to patient's perception. In addition, no statistically significant differences between treatments were observed for patient's global satisfaction with onset of effect and global expectation of treatment adherence. For the exploratory variable change in FEV1 from predose to postdose, indacaterol showed superiority over placebo with a clinically relevant least-squares mean treatment difference of 0.12 L (P

BackgroundApproximately 50% of patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report hives and angioedema; some experience hives/angioedema only.ObjectiveAssess omalizumab's effect on angioedema and quality of life (QoL) in subgroups with refractory CIU/CSU: those with and without angioedema.MethodsPatients received omalizumab (75, 150 or 300 mg) or placebo every 4 weeks for 12/24 weeks. Angioedema and QoL were assessed [Urticaria Patient Daily Diary and Dermatology Quality of Life Index (DLQI)]. Subgroups were based on the presence/absence of baseline angioedema 7 days prior to randomization.ResultsPatients with baseline angioedema randomized to omalizumab 300 mg had a greater reduction in mean weekly incidence of angioedema and mean number of days/week with angioedema vs. placebo at 12 and 24 weeks. A 3.3- to 4.5-point greater mean reduction in DLQI score was achieved with omalizumab 300 mg treatment vs. placebo, above the minimal clinically important difference threshold. Results with lower doses vs. placebo were variable.ConclusionCompared with placebo, omalizumab 300 mg treatment over 12-24 weeks resulted in marked reduction in incidence and number of days/week with angioedema accompanied by clinically relevant improvement in QoL.

Abstract Background This research was conducted to confirm the validity and reliability and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t™, a questionnaire specifically designed to measure patient-reported outcomes (PRO) associated with toenail onychomycosis. Methods 504 patients with toenail onychomycosis randomized to receive 12 weeks of terbinafine 250 mg/day with or without target toenail debridement in the IRON-CLAD® trial completed the OnyCOE-t™ at baseline, weeks 6, 12, 24, and 48. The OnyCOE-t™ is composed of 6 multi-item scales and 1 single-item scale. These include a 7-item Toenail Symptom assessment, which comprises both Symptom Frequency and Symptom Bothersomeness scales; an 8-item Appearance Problems scale; a 7-item Physical Activities Problems scale; a 1-item Overall Problem scale; a 7-item Stigma scale; and a 3-item Treatment Satisfaction scale. In total, 33 toenail onychomycosis-specific items are included in the OnyCOE-t™. Clinical data, in particular the percent clearing of mycotic involvement in the target toenail, and OnyCOE-t™ responses were used to evaluate the questionnaire's reliability, validity, responsiveness, and the minimally clinical important difference (MCID). Results The OnyCOE-t™ was shown to be reliable and valid. Construct validity and known groups validity were acceptable. Internal consistency reliability of multi-item scales was demonstrated by Cronbach's alpha > .84. Responsiveness was good, with the Treatment Satisfaction, Symptom Frequency, Overall Problem, and Appearance Problem scales demonstrating the most responsiveness (Guyatt's statistic of 1.72, 1.31, 1.13, and 1.11, respectively). MCID was evaluated for three different clinical measures, and indicated that approximately an 8.5-point change (on a 0 to 100 scale) was clinically meaningful based on a 25% improvement in target nail clearing. Conclusion The OnyCOE-t™ questionnaire is a unique, toenail-specific PRO questionnaire that can be used with confidence in future studies of toenail onychomycosis. MCID was evaluated for three different clinical measures, and indicated that approximately a 7-point change (on a 0 to 100 scale) was clinically meaningful based on a 12.5% improvement in target nail clearing.

Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18 F-2-fluorodeoxyglucose-positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was -0.053 (95% confidence interval = -0.169 to 0.064; P= 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P= 0.0063) and ferritin (P= 0.0354), and an increase in fetuin-A (P= 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cluster analysis (CA) is a frequently used applied statistical technique that helps to reveal hidden structures and "clusters" found in large data sets. However, this method has not been widely used in large healthcare claims databases where the distribution of expenditure data is commonly severely skewed. The purpose of this study was to identify cost change patterns of patients with end-stage renal disease (ESRD) who initiated hemodialysis (HD) by applying different clustering methods., Methods: A retrospective, cross-sectional, observational study was conducted using the Truven Health MarketScan® Research Databases. Patients aged ≥18 years with ≥2 ESRD diagnoses who initiated HD between 2008 and 2010 were included. The K-means CA method and hierarchical CA with various linkage methods were applied to all-cause costs within baseline (12-months pre-HD) and follow-up periods (12-months post-HD) to identify clusters. Demographic, clinical, and cost information was extracted from both periods, and then examined by cluster., Results: A total of 18,380 patients were identified. Meaningful all-cause cost clusters were generated using K-means CA and hierarchical CA with either flexible beta or Ward's methods. Based on cluster sample sizes and change of cost patterns, the K-means CA method and 4 clusters were selected: Cluster 1: Average to High (n = 113); Cluster 2: Very High to High (n = 89); Cluster 3: Average to Average (n = 16,624); or Cluster 4: Increasing Costs, High at Both Points (n = 1554). Median cost changes in the 12-month pre-HD and post-HD periods increased from $185,070 to $884,605 for Cluster 1 (Average to High), decreased from $910,930 to $157,997 for Cluster 2 (Very High to High), were relatively stable and remained low from $15,168 to $13,026 for Cluster 3 (Average to Average), and increased from $57,909 to $193,140 for Cluster 4 (Increasing Costs, High at Both Points). Relatively stable costs after starting HD were associated with more stable scores on comorbidity index scores from the pre-and post-HD periods, while increasing costs were associated with more sharply increasing comorbidity scores., Conclusions: The K-means CA method appeared to be the most appropriate in healthcare claims data with highly skewed cost information when taking into account both change of cost patterns and sample size in the smallest cluster.

Objective: To describe secondary analyses from a 12-week, randomized, open-label trial where adult schizophrenia outpatients receiving risperidone, olanzapine, or aripiprazole were switched to iloperidone., Methods: Patients were randomized into two groups: one where the antecedent antipsychotic dose was titrated downwards to zero over 2 weeks (n=240), and the other group where the antecedent antipsychotic was abruptly stopped (n=260). Adaptations of the Clinical Global Impression scale were used to evaluate clinical changes. Other assessments included the reporting of adverse events (AEs), study discontinuation, body weight, and metabolic variables., Results: Improvement was steady throughout the study for both gradual- and immediate-switch groups starting at Week 1 and continuing through Week 12. Discontinuations due to AEs in the first 2 weeks of treatment were higher for the immediate-switch group compared with the gradual-switch group (10.8% vs. 5.4%, NNT 19, 95% CI 10-151). Fewer patients in the gradual-switch group experienced dizziness as an AE, whereas a higher percentage of patients in the immediate-switch group exhibited earlier onset of a therapeutic response within the first 2 weeks; both groups were comparable thereafter with low rates of dizziness and similar efficacy outcomes., Conclusions: Switching to iloperidone can be accomplished either with a gradual crossover or immediate discontinuation of the prior antipsychotic; however, the immediate-switch method is associated with greater proportion of initial dizziness. The observed outcomes are consistent with what has been previously reported regarding iloperidone's favorable akathisia/EPS profile and modest impact on somnolence/sedation, body weight, and metabolic variables.

Background: This research was conducted to confirm the validity and reliability and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t, a questionnaire specifically designed to measure patient-reported outcomes (PRO) associated with toenail onychomycosis., Methods: 504 patients with toenail onychomycosis randomized to receive 12 weeks of terbinafine 250 mg/day with or without target toenail debridement in the IRON-CLAD trial completed the OnyCOE-t at baseline, weeks 6, 12, 24, and 48. The OnyCOE-t is composed of 6 multi-item scales and 1 single-item scale. These include a 7-item Toenail Symptom assessment, which comprises both Symptom Frequency and Symptom Bothersomeness scales; an 8-item Appearance Problems scale; a 7-item Physical Activities Problems scale; a 1-item Overall Problem scale; a 7-item Stigma scale; and a 3-item Treatment Satisfaction scale. In total, 33 toenail onychomycosis-specific items are included in the OnyCOE-t. Clinical data, in particular the percent clearing of mycotic involvement in the target toenail, and OnyCOE-t responses were used to evaluate the questionnaire's reliability, validity, responsiveness, and the minimally clinical important difference (MCID)., Results: The OnyCOE-t was shown to be reliable and valid. Construct validity and known groups validity were acceptable. Internal consistency reliability of multi-item scales was demonstrated by Cronbach's alpha > .84. Responsiveness was good, with the Treatment Satisfaction, Symptom Frequency, Overall Problem, and Appearance Problem scales demonstrating the most responsiveness (Guyatt's statistic of 1.72, 1.31, 1.13, and 1.11, respectively). MCID was evaluated for three different clinical measures, and indicated that approximately an 8.5-point change (on a 0 to 100 scale) was clinically meaningful based on a 25% improvement in target nail clearing., Conclusion: The OnyCOE-t questionnaire is a unique, toenail-specific PRO questionnaire that can be used with confidence in future studies of toenail onychomycosis. MCID was evaluated for three different clinical measures, and indicated that approximately a 7-point change (on a 0 to 100 scale) was clinically meaningful based on a 12.5% improvement in target nail clearing.