Improved Survival Outcomes in Patients With MET-Dysregulated Advanced NSCLC Treated With MET Inhibitors: Results of a Multinational Retrospective Chart Review.

BACKGROUND: We evaluated the disease and patient characteristics, treatment, and MET testing patterns, predictive biomarkers and survival outcomes in patients with MET-dysregulated metastatic non-small-cell lung cancer (NSCLC) in a real-world setting. PATIENTS AND METHODS: This was a multinational, retrospective, noninterventional chart review study. Data from medical records of patients with advanced/metastatic EGFR wild-type, MET-dysregulated NSCLC (December 2017-September 2018) were abstracted into electronic data collection forms. RESULTS: Overall, 211 patient charts were included in this analysis; 157 patients had MET exon 14 skipping mutations (METex14; with or without concomitant MET amplification) and 54 had MET amplification only. All patients were tested for METex14, whereas MET amplification was evaluated in 168 patients. No overlap was reported between MET dysregulation and ALK, ROS1 or RET rearrangements, or HER2 exon 20 insertions. Overall, 56 of 211 patients (26.5%) received MET inhibitor (METi) therapy in any treatment-line setting (31.2% in the METex14 cohort; 13% in the MET-amplified only cohort). In the METex14 cohort, median OS in patients receiving METi was 25.4 months versus 10.7 months in patients who did not (HR [95% CI]: 0.532 [0.340-0.832]; P = .0055). In the MET-amplified only cohort, median OS was 20.6 months in patients treated with METi compared with 7.6 months in those without METi (HR [95% CI]: 0.388 [0.152-0.991]; P = .0479). CONCLUSIONS: MET alterations in NSCLC typically occur in the absence of other oncogenic driver mutations and are associated with poor survival outcomes. Notably, METi therapies are associated with improved survival outcomes in patients with MET-dysregulated NSCLC.

Understanding the patient experience and treatment benefits in patients with non-small-cell lung cancer with brain metastasis.

BACKGROUND: Despite the high prevalence of brain metastases (BM) secondary to non-small-cell lung cancer (NSCLC) (NSCLC/BM), patients' experiences (symptoms and impacts) are not fully understood. This study sought to understand the patient experience with NSCLC/BM and identify a patient-reported outcome (PRO) measure fit to capture the most important NSCLC/BM symptoms and impacts. METHODS: A targeted literature review was completed; the National Comprehensive Cancer Network (NCCN)/Functional Assessment of Cancer Therapy-Brain Symptom Index, 24-item version (NFBrSI-24) was identified as a relevant measure that assessed the core symptoms and impacts associated with NSCLC/BM. Qualitative interviews composed of concept elicitation and cognitive debriefing with oncologists (n = 3) and adult patients (n = 16) with NSCLC/BM were conducted to confirm the content validity and evaluate the relevance and appropriateness of the NFBrSI-24 for this condition. RESULTS: The NSCLC/BM symptoms and impacts identified in the literature and reported by oncologists and patients were consistent and captured in the NFBrSI-24. Study participants reported significant burden associated with the symptoms (commonly fatigue, headache) and impacts of NSCLC/BM. Participants indicated that the NFBrSI-24 captured their most salient experiences with NSCLC/BM and that symptom improvement or a delay in progression, as measured by the NFBrSI-24, would be meaningful. During the cognitive debriefing, participants generally indicated that the NFBrSI-24 was comprehensive and easy to understand/answer and that it assessed symptoms they considered most important to treat. CONCLUSIONS: These results suggest that the NFBrSI-24 adequately captures an appropriate measure of NSCLC/BM symptoms and impact.

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study.

INTRODUCTION: Capmatinib, a MET inhibitor, showed substantial antitumour activity with manageable side effects in patients with MET exon 14 (METex14)-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 study. We report patient-reported outcomes (PROs) from this study. METHODS: Enrolled treatment-naïve (1L) or pre-treated (2L+) patients with aNSCLC with a METex14-skipping mutation received 400 mg capmatinib twice daily during 21-day treatment cycles. PROs were collected at baseline and every six weeks thereafter using EORTC QLQ-C30 global health status/quality of life (GHS/QoL), QLQ-LC13 symptoms, and EQ-5D-5L visual analogue scale (VAS) questionnaires. RESULTS: As of 6 January 2020, 27/28 1L and 65/69 2L+ patients had completed PROs at baseline; compliance rates remained >70%. Cough improved early, with meaningful improvements (≥10-point change from baseline) observed throughout cycles (mean change from baseline [SD] by week 7: 1L -13.0 [39.9], 2L+ -8.2 [28.4]; week 43: 1L -28.2 [26.7], 2L+ -10.5 [27.3]). QoL, assessed by GHS/QoL and VAS, improved by week 7 in 1L and 2L+ patients, with improvements generally sustained over time. Median time to definitive deterioration (TTDD) in GHS/QoL was 16.6 months (95% CI: 9.7, not estimable [NE]) in 1L and 12.4 months (95% CI: 4.2, 19.4) in 2L+ patients. Median TTDD for dyspnoea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE) for 1L and 2L+ patients, respectively, and NE for cough and chest pain. CONCLUSIONS: Capmatinib was associated with clinically meaningful improvements in cough and preserved QoL, further supporting its use in patients with METex14-mutated aNSCLC. TRIAL REGISTRATION: ClinicalTrials.gov registry number: NCT02414139.

Secukinumab and Sustained Reduction in Fatigue in Patients With Ankylosing Spondylitis: Long-Term Results of Two Phase III Randomized Controlled Trials.

OBJECTIVE: To investigate the longer-term effects of secukinumab 150 mg on fatigue in patients with ankylosing spondylitis (AS) in the MEASURE 1 study (up to 3 years) and the MEASURE 2 study (up to 2 years). METHODS: Patients with active AS were randomized to secukinumab or placebo in MEASURE 1 (10 mg/kg intravenous [IV] followed by 150 mg subcutaneous) and MEASURE 2 (150 mg subcutaneous). Patients were naive to treatment with anti-tumor necrosis factor (anti-TNF-naive) therapy or had an inadequate response/intolerance to anti-TNF therapy (anti-TNF-IR). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Relationships between fatigue response and baseline characteristics and clinical/laboratory variables were explored. RESULTS: Significant improvements in FACIT-F scores from baseline were observed with secukinumab across both studies versus placebo at week 16 (P < 0.05). Improvements were sustained through week 156 (MEASURE 1) and week 104 (MEASURE 2). Significantly more patients reported fatigue responses (FACIT-F improvement ≥4; observed data) with secukinumab 150 mg than with placebo at week 16 in both MEASURE 1 (P < 0.05) and MEASURE 2 (P < 0.01). Fatigue responses were achieved by 75.6% of patients receiving secukinumab at week 156 (MEASURE 1) and 81.4% at week 104 (MEASURE 2); these results were consistent in patients who were anti-TNF-naive (74.3% and 84.6%, respectively) and anti-TNF-IR (81.3% and 75.0%, respectively). Baseline characteristics did not predict improvement in fatigue consistently. Fatigue responses were moderately to strongly correlated with responses in several clinical measures, including the Assessment of SpondyloArthritis international Society (ASAS) 20%/40% improvement, ASAS5/6 responses, the Ankylosing Spondylitis Disease Activity Score with C-reactive protein level, the Bath Ankylosing Spondylitis Disease Activity Index, and the Short Form 36 health questionnaire scores. CONCLUSION: Secukinumab provided rapid and sustained improvements in fatigue for up to 3 years, regardless of prior anti-TNF exposure.

Exploring determinants of psoriasis patients' treatment choices: a discrete-choice experiment study in the United States and Germany.

BACKGROUND: Biologic psoriasis treatments are differentiated by efficacy, side effects, and other attributes. OBJECTIVE: Determine attributes of biologic psoriasis treatments that drive patients' treatment choices. METHODS: Respondents (USA: n = 300; Germany: n = 300) with moderate-to-severe psoriasis completed a discrete-choice-experiment survey, choosing between hypothetical treatments characterized by attributes with varying levels: chance of clear skin after 1 year, number of first-year treatments, first-year risks of mild-to-moderate injection site reaction (ISR) and serious infection, and years of proven efficacy/safety. RESULTS: U.S. respondents most valued clear skin (conditional relative importance, 1.88; p < .05). While other attributes were of generally equivalent importance, ISR risk outweighed serious-infection risk (1.06 vs. 0.70; p < .05). German respondents placed greatest importance on ISR risk (1.61; p < .05) and clear skin (1.49; p < .05). LIMITATIONS: Respondents evaluated hypothetical treatments and were recruited from web panels. CONCLUSIONS: Clear skin and ISR risk are stronger drivers of treatment choice than injection frequency and infection risk.

The effect of secukinumab on patient-reported outcomes in patients with active psoriatic arthritis in a randomised phase 3 trial.

BACKGROUND: The phase 3 FUTURE 5 trial (NCT02404350) showed the clinical and radiographical efficacy of secukinumab in patients with psoriatic arthritis. This analysis aimed to assess the effect of secukinumab on patient-reported outcomes (PROs). METHODS: FUTURE 5 was a phase 3, multicentre, parallel-group randomised trial in which patients who were 18 years old or older, met the classification criteria for psoriatic arthritis at screening, and had symptoms of moderate-to-severe psoriatic arthritis for at least 6 months were randomly assigned to receive secukinumab 300 mg, 150 mg, 150 mg no loading dose (NL), or placebo weekly from baseline to week 4 and every 4 weeks thereafter. The prespecified PROs of the FUTURE 5 trial were assessed first in the overall population. We report mean changes from baseline and the proportion of patients reporting improvements equal to or more than the minimum clinically important differences (MCIDs) and scores equal to or more than the normative values for patient global assessments (PtGA) of disease activity; psoriasis and arthritis visual analogue scale (VAS) scores; pain VAS; Health Assessment Questionnaire Disability Index (HAQ-DI); 36-item Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F); and quality of life questionnaires. Patients were then stratified and assessed according to their tumour necrosis factor (TNF) inhibitor status (TNF-naive and TNF-inadequate responder [TNF-IR] populations) as a post-hoc analysis. FINDINGS: Patients in all secukinumab groups reported significant least-squares mean changes from placebo at week 16 in all PROs except SF-36 mental component summary (MCS), irrespective of TNF inhibitor use. These included PtGA (300 mg difference vs placebo -12·2 [95% CI -16·3 to -8·1], 150 mg -8·22 [-12·4 to -4·1], 150 mg NL -8·3 [-12·5 to -4·2]; all p<0·0001), pain VAS (300 mg -14·3 [-18·3 to -10·2], 150 mg -11·5 [-15·6 to -7·5], 150 mg NL -11·3 [-15·3 to -7·2]; all p<0·0001), HAQ-DI (300 mg -0·33 [-0·42 to -0·24], 150 mg -0·23 [-0·32 to -0·14], 150 mg NL -0·24 [-0·33 to -0·15]; all p<0·0001), and FACIT-F (300 mg 4·8 [3·2 to 6·4], 150 mg 4·2 [2·6 to 5·8], 150 mg NL 3·5 [1·9 to 5·1]; all p<0·0001). Similarly, the proportion of patients with improvements equal to or better than MCID at week 16 was higher in the secukinumab group compared with the placebo group for most PROs except SF-36 (MCS), regardless of TNF inhibitor use. INTERPRETATION: Secukinumab resulted in early, statistically significant, clinically meaningful, sustained improvements in PROs across all doses compared with placebo in patients with active psoriatic arthritis. These improvements were seen irrespective of previous TNF inhibitor use, in a post-hoc analysis. These results indicate that secukinumab provides comprehensive improvement for patients with psoriatic arthritis, regardless of previous therapy. FUNDING: Novartis.

Patient-reported outcomes are important elements of psoriasis treatment decision making: A discrete choice experiment survey of dermatologists in the United States.

BACKGROUND: Psoriasis Area and Severity Index (PASI) response rates have been the benchmark for evaluating treatment efficacy in trials involving moderate-to-severe psoriasis. OBJECTIVE: To understand how dermatologists assess biologics and which trade-off rules they apply when planning psoriasis treatment. METHODS: Two online surveys of 130 and 129 US dermatologists (surveys 1 and 2, respectively) were conducted with use of direct and indirect elicitation via discrete choice experiment. Respondents were asked to choose hypothetical biologics on the basis of 6 attributes (a ≥75% reduction from baseline in PASI score or a ≥90% reduction from baseline in PASI score, infection risk, dosing frequency, and 3 patient-reported outcomes [PROs] [relief of depression, relief of itching, and impact on usual activities]). RESULTS: Most dermatologists (74% in survey 1 and 76% in survey 2) reported using both PASI and PROs when selecting a biologic. PASI response rate was the most important attribute (35%-38% of overall decision weight), whereas combined PRO attributes had similar importance (36% of decision weight). Infection risk and dosing frequency influenced the decision to a lesser extent. LIMITATIONS: Potential bias in considering 3 PROs versus 1 PASI rate and 1 safety attribute. CONCLUSION: PASI is most important for dermatologists selecting biologics, but PROs are also considered, especially when PASI response rate is similar between treatments. PRO data should be collected in trials involving moderate-to-severe psoriasis.

Dose increase beyond labelled dose of biologics is associated with incremental pharmacy costs: results from a real-world study in the UK.

Background: There is limited evidence regarding biologics dosing patterns and its costs among psoriasis patients in the United Kingdom (UK). Objective: This retrospective study assessed biologics dose increase beyond labelled dose and associated UK pharmacy costs in moderate to severe psoriasis patients. Methods: Adult psoriasis patients on biologic prescription for ≥12 continuous months between January 2010 and March 2015 with their diagnosis recorded in the UK Hospital Treatment Insights Database within one month of such prescription were included. The proportion of patients receiving ≥30% higher the average daily maintenance dose as per the UK product label, and associated 12-month costs were reported. Results: The study included 362 patients, receiving adalimumab (48%), etanercept (17%), ustekinumab (12%), and infliximab (23%). Beyond labelled dose increase was noted in 14% adalimumab, 20% etanercept, 18% ustekinumab and 28% infliximab patients with an associated mean annual extra cost per patient of £7936, £5912, £2422 and £2275, respectively. Conclusion: Dose increase beyond labelled dose of biologics was commonly observed in moderate to severe psoriasis in the UK and resulted in substantial annual incremental pharmacy costs.

Evaluating the cost-effectiveness of secukinumab in moderate-to-severe psoriasis: a Japanese perspective.

AIM: To evaluate the cost-effectiveness of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, compared to other clinically used biologics (adalimumab, infliximab, and ustekinumab) in Japan for the treatment of moderate-to-severe psoriasis from the healthcare system (total costs) and patient co-payment (using different frequencies of drug purchase) perspectives. METHODS: A decision-tree (first year)/Markov model (subsequent years), with an annual cycle, was developed. The model adopted a 5-year time horizon. Efficacy inputs were obtained from a mixed-treatment comparison analysis, and other model inputs were collected from published literature and local Japanese sources. Model outcomes included quality-adjusted life years (QALYs) and an incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained. The annual discounting rate of 2% was applied to both costs and outcomes. RESULTS: Results for the healthcare system perspective showed that secukinumab had the highest number of quality-adjusted life years (QALYs) (4.07) vs other biologics, dominated ustekinumab and infliximab, and the ICER of secukinumab compared to adalimumab was ¥8,418,222/QALY gained. In the patient co-payment perspective with the monthly purchase of drugs, ustekinumab had the lowest co-payment cost, followed by infliximab, adalimumab, and secukinumab. In the patient co-payment perspective with a once every 3 months purchase of secukinumab and adalimumab, the co-payment costs of secukinumab, adalimumab, and ustekinumab became comparable, and infliximab had the highest co-payment cost. LIMITATIONS: Only short-term efficacy data was modeled, as there was a lack of data on long-term outcomes. Treatment sequencing was restricted to first-line biologic treatment. Drop-out rates for comparators were assumed to be equivalent to secukinumab in the absence of available data. CONCLUSIONS: Secukinumab is a cost-efficient treatment for moderate-to-severe psoriasis, providing greater health outcomes to patients at lower total costs compared to infliximab and ustekinumab, as well as comparable patient co-payment relative to other biologic treatments.

Secukinumab is Superior to Ustekinumab in Clearing Skin in Patients with Moderate to Severe Plaque Psoriasis (16-Week CLARITY Results).

INTRODUCTION: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab. METHODS: In the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator's Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients' quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized. RESULTS: Both co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%). CONCLUSION: The results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov Identifier, NCT02826603. FUNDING: Novartis Pharma AG, Basel, Switzerland.

Disease Burden and Treatment Patterns of Psoriasis in Russia: A Real-World Patient and Dermatologist Survey.

INTRODUCTION: Data regarding disease burden and quality of life (QoL) for patients with psoriasis from Russia are limited. The objective of this study was to describe the demographic and clinical characteristics, comorbidities, and treatment patterns of systemic therapy eligible psoriasis patients in Russia in order to assess the impact of psoriasis on the QoL and work productivity of the patients and to evaluate patient/dermatologist concordance on disease severity, signs/symptoms, and satisfaction with psoriasis treatment. METHODS: Data were collected by the Growth from Knowledge Disease Atlas global real-world evidence programme from nine countries. The data from the Russian population are presented here. Adult patients who had a current or prior history of moderate-to-severe psoriasis and were receiving prescription treatment at the time of the survey were included. Dermatologist-reported data on disease severity, symptoms, comorbidities, and treatment as well as patient-reported data on QoL and work productivity were collected. Descriptive analysis of the data was conducted. Patient/dermatologist concordance was assessed using Cohen's κ. RESULTS: A total of 300 patients from Russia were included. The mean Psoriasis Area and Severity Index score was 9.0 and the mean disease duration was 9.9 years. The proportion of patients with itch, skin pain, and comorbidities increased as current psoriasis severity increased. The disease had a negative impact on patients' QoL (mean Dermatology Life Quality Index score: 7.1) and work productivity (33.2% drop in work productivity), which further deteriorated as disease severity increased. A large proportion of the enrolled patients (60%) were treated with topical agents only. Overall, the level of concordance between patients and their dermatologists regarding psoriasis severity and satisfaction with overall disease control achieved was low. CONCLUSION: Results demonstrate a substantial disease burden on psoriasis patients in Russia, despite receiving treatment for their psoriasis, as well as low patient/dermatologist concordance of views on treatment outcomes. These findings also highlight a need to further incorporate the patient's views into treatment decision-making in Russia. FUNDING: Novartis Pharma AG, Basel, Switzerland.

Higher Psoriasis Skin Clearance Is Associated with Lower Annual Indirect Costs in the United States: A Post Hoc Analysis from the CLEAR Study.

BACKGROUND: Psoriasis is associated with a high economic burden to society. New psoriasis systemic treatments offer the potential for improved skin clearance. Whether a higher degree of clearing translates into economic benefit through decreased work impairment has not been fully determined. OBJECTIVE: To assess whether more complete clearing of psoriasis is associated with a reduction in disease-related indirect costs. METHODS: Pooled data from employed patients included in the CLEAR study, a phase 3b study comparing the efficacy and safety of secukinumab (337 subjects) versus ustekinumab (339 subjects), were classified into 4 levels of skin clearance improvement at weeks 16 and 52: Psoriasis Area and Severity Index (PASI) improvement from baseline of < 50% (PASI < 50), 50%-74% (PASI 50-74), 75%-89% (PASI 75-89), and ≥ 90% (PASI ≥ 90). Patients completed the Work Productivity and Activity Impairment questionnaire for psoriasis (WPAI-PSO), which assessed absenteeism, presenteeism, and a composite overall work impairment over the previous 7 days at weeks 16 and 52. U.S. Department of Labor data were used to calculate annual indirect costs due to work productivity loss. RESULTS: In the CLEAR study, 452 (67%) were employed at baseline and included in this analysis. At week 16, mean overall work impairment significantly decreased with higher PASI improvements: 22.8% for PASI < 50, compared with 13.3% for PASI 50-74 (P = 0.001); 6.4% for PASI 75-89 (P < 0.001); and 4.9% for PASI ≥ 90 (P < 0.001), with the majority of work impairment related to presenteeism. Calculated mean work hours lost by overall work impairment decreased with higher PASI improvements: 8.2 hours lost/week (429 hours/year) for patients with PASI 50; 4.6 hours lost/week (251 hours/year) for PASI 50-74; 2.3 hours lost/week (121 hours/year) for PASI 75-89; and 1.8 hours lost/week (93 hours/year) for PASI ≥ 90. Associated mean annual indirect costs due to work productivity loss per worker decreased with higher PASI improvements: $10,318 for PASI < 50, $6,042 for PASI 50-74, $2,901 for PASI 75-89, and $2,233 for PASI ≥ 90. Similar results were observed at week 52. Mean overall work impairment decreased with higher PASI improvements, ranging from 26.3% for PASI < 50 to 6.9% for PASI ≥ 90. A decrease in overall work hours lost (ranging from 9.5 hours lost/week [495 hours/year] for PASI < 50 to 2.5 hours/week [130 hours/year] for PASI ≥ 90), as well as associated annual indirect costs due to work productivity loss (ranging from $11,906 for PASI < 50 to $3,125 for PASI ≥ 90), were also shown with higher PASI improvements at week 52. CONCLUSIONS: Among working patients with moderate to severe psoriasis, higher PASI improvements were associated with lower work productivity loss and reduced annual indirect costs. By improving and sustaining skin clearance, psoriasis treatments may contribute to increased work productivity and decreased societal economic burden. DISCLOSURES: Funding for this study was provided by Novartis Pharmaceuticals. Zhao and Herrera are employed by Novartis. Gilloteau is employed by Novartis Pharma AG. McBride, Graham, and Miles are employed by RTI Health Solutions, which provides consulting and other research services to pharmaceutical, device, governmental, and nongovernmental organizations and received funding from Novartis for manuscript development, analysis development, and general consultation. Feldman reports grants and personal fees from Novartis, Abbvie, Janssen, Lilly, and Celgene, along with personal fees from Amgen and Valeant.

Effect of secukinumab on quality of life and psoriasis-related symptoms: A comparative analysis versus ustekinumab from the CLEAR 52-week study.

BACKGROUND: Secukinumab has demonstrated greater sustained skin clearance than ustekinumab through week 52, greater improvement in symptoms and health-related quality of life, and comparable safety profile. OBJECTIVE: To assess the impact of secukinumab versus that of ustekinumab on complete relief from psoriasis-related symptoms, time to response in terms of health-related quality of life, and cumulative benefit among patients with moderate-to-severe plaque psoriasis. METHODS: Psoriasis-related pain, itching, and scaling and the Dermatology Life Quality Index (DLQI) score were compared between treatments on the basis of time to complete relief of symptoms and time to DLQI response in the CLEAR trial. Cumulative benefit over 52 weeks based on Psoriasis Area and Severity Index score, symptom relief, and DLQI response were evaluated by area under the curve analysis. RESULTS: Significantly more patients treated with secukinumab achieved complete relief of pain at weeks 16 and 52 (all P < .05). Complete relief of itching and scaling occurred significantly faster with secukinumab (median, 4 weeks faster for itching and 8 weeks faster for scaling [P < .001]). Response as measured by the DLQI was 4 weeks faster with secukinumab (P < .0001). Cumulative benefits were greater with secukinumab (all P < .05). LIMITATIONS: Analyses were post hoc. CONCLUSION: This patient-reported outcome analysis confirms greater and sustained benefits of secukinumab versus those of ustekinumab treatment on patients' lives.

Economic burden of comorbidities in psoriasis patients in the United States: results from a retrospective U.S. database.

BACKGROUND: Psoriasis is a multifactorial, inflammatory, skin disease associated with various comorbidities. The cost of those comorbidities is not well characterized. The present study assesses the incremental burden of comorbidities on healthcare resource utilization, direct costs and indirect costs associated with short-term disabilities among patients with psoriasis in the United States. METHODS: A retrospective, U.S. cohort analysis was conducted using a large claims database. Adult psoriasis patients with at least two diagnoses of psoriasis during the years 2010 and 2011 (one psoriasis diagnosis had to happen in the year 2010) and with continuous enrollment of medical and pharmacy benefits in the years 2010 and 2011 were included. Psoriasis patients were categorized and compared according to the presence or absence of pre-selected comorbidities in the year 2010. Adjusted annual direct (costs associated with outpatient, emergency room, and inpatient claims, and outpatient pharmacy claims) and indirect costs (short-term disabilities) was assessed in patients with and without comorbidities using a regression analysis, controlling for age, gender, and psoriasis severity in year 2010. RESULTS: In total, 56,406 patients (mean [SD]) age, 51.6 [14.6] years) were included in the analysis. The most prevalent comorbidities were hypertension (34.3%), hyperlipidemia (33.5%), cardiovascular disease (17.7%), diabetes (14.2%), and psoriatic arthritis (9.9%). Psoriasis patients with comorbidities used more healthcare resources than those without comorbidities. The incidence rate ratio (IRR) (95% CI) for patients with cardiovascular disease was 1.5 (1.4 - 1.5) for outpatient visits, 2.6 (2.4 - 2.8) for hospitalizations, and 2.3 (2.2 - 2.5) for ER visits, showing higher IRRs across all three types of resource use. The mean annual adjusted direct cost differences (i.e., incremental adjusted costs) in psoriasis patients with and without comorbidities were $9914.3, $8386.5, and $8275.1 for psoriatic arthritis, peripheral vascular disease, and cardiovascular disease, respectively. The mean annual incremental adjusted indirect costs of short-term disabilities were $1333, $1195, $994.9, and $996.6 for cerebrovascular disease, obesity, peripheral vascular disease, and depression, respectively. CONCLUSION: The presence of comorbidities was associated with higher healthcare resource utilization and costs among patients with psoriasis.

Psoriasis patients with psoriasis Area and Severity Index (PASI) 90 response achieve greater health-related quality-of-life improvements than those with PASI 75-89 response: results from two phase 3 studies of secukinumab.

BACKGROUND: The emergence of new biological therapies showing high and sustained level of Psoriasis Area and Severity Index (PASI) 90 response has provided the possibility of both greater skin clearance and increased quality of life (QOL). OBJECTIVE: To evaluate the association of greater response in skin clearance with improvements in skin-related QOL up to 52 weeks. METHODS: Subjects achieving various levels of skin clearance (PASI 90-100 or PASI 75-89) and Dermatology Life Quality Index (DLQI) (0/1) response were compared using ERASURE and FIXTURE trial data. Similar analyses with IGA ratings of Clear or Almost Clear were performed. RESULTS: Significantly more PASI 90-100 responders at week 12 had DLQI 0/1 response than PASI 75-89 (69.4% vs. 47.1%; p < .001) and sustained DLQI 0/1 response at week 52 (74.0% vs. 56.7%; p < .001). IGA results were similar. CONCLUSIONS: These results show that PASI 90-100 is a relevant therapeutic goal in moderate to severe psoriasis compared to PASI 75-89 when considering patients' QOL.

Secukinumab sustains early patient-reported outcome benefits through 1 year: Results from 2 phase III randomized placebo-controlled clinical trials comparing secukinumab with etanercept.

BACKGROUND: Psoriasis is a chronic condition with negative impact on patients' quality of life that most often requires lifelong effective and safe treatment. OBJECTIVE: This analysis focused on the effect of secukinumab treatment on patient-reported health-related quality of life as assessed by the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis. METHODS: The proportion of subjects achieving DLQI score 0/1 response at week 24, time to DLQI score 0/1 response, and sustained DLQI score 0/1 response up to week 52 were compared between secukinumab and etanercept. RESULTS: Of 1470 subjects, 1144 received secukinumab and 326 received etanercept. DLQI score 0/1 response rates were significantly higher for secukinumab than for etanercept at week 24. The median time to DLQI score 0/1 response was significantly shorter for secukinumab versus etanercept (12 vs 24 weeks; P < .01). The majority of secukinumab-treated subjects achieved DLQI score 0/1 response at week 24 and sustained it through week 52 along with a 90% to 100% reduction in the Psoriasis Area and Severity Index total score response. LIMITATIONS: Placebo comparisons are limited during the maintenance period because of rerandomization at week 12. CONCLUSION: Secukinumab treatment provided faster and greater sustained improvements in quality of life than etanercept over 52 weeks, consistent with greater clinical response.

Caring for relatives with lung cancer in Europe: an evaluation of caregivers' experience.

PURPOSE: Informal caregiving for cancer patients is associated with substantial costs and negative health impact. This study investigated the health, humanistic and economic consequences of caring for lung cancer patients in five European Union (EU) countries. METHODS: The study included respondents to the 2010/2011 EU National Health and Wellness Survey from France, Germany, Italy, Spain and the United Kingdom who self-reported being caregivers of a relative with lung cancer (n = 107) or non-caregivers (n = 103,868). Bivariate and multivariable analyses tested the association of caregiving with stress-related comorbidities; health-related quality of life (HRQoL), using the Short Form-12; healthcare resource use; and work productivity/activity impairment, using the Work Productivity and Activity Impairment (WPAI) questionnaire. Costs were based on absenteeism and presenteeism rates. RESULTS: Caregivers versus non-caregivers had significantly higher odds of depression, insomnia, headache and gastrointestinal symptoms, and worse HRQoL. Caregivers reported significantly higher rates of presenteeism-related, overall work and activity impairment; higher odds of impairment across WPAI measures; and higher annual indirect costs with presenteeism and overall work impairment. CONCLUSIONS: Caregiving for lung cancer patients is associated with significant health/work impairments and costs, highlighting a need for increased, personalized caregiver support.

Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges.

BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2(nd) generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation.