Once-Daily Triple Therapy in Patients with COPD: Patient-Reported Symptoms and Quality of Life

Introduction

Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies. The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses. FULFIL co-primary endpoint data have been previously reported.

Methods

FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β₂-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations. A subset participated for 52 weeks. Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD? (E-RS: COPD), St George’s Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.

Results

FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period. FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR. At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).

Conclusion

These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR. The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.

Trial registration

ClinicalTrials.gov number: NCT02345161.

Funding

GSK.

     

Evaluating the Impact and Benefits of Fluticasone Furoate/Vilanterol in Individuals with Asthma or COPD: A Mixed-Methods Analysis of Patient Experiences

Introduction

This study evaluated patients’ experiences with fluticasone furoate/vilanterol (FF/VI) combination therapy in UK patients with asthma or chronic obstructive pulmonary disease (COPD).

Methods

Participants aged ≥?18 years, with self-reported, physician-diagnosed asthma or COPD (≥?1 year) who had been receiving FF/VI (≥?3 months) were recruited from UK primary care. This two-phase, mixed-methods study consisted of a semi-structured, telephone-interview phase (qualitative) and a self-completed online/paper-survey phase (quantitative).

Results

The telephone-interview phase included 50 individuals [asthma, n?=?25; COPD, n?=?25; mean age (SD) 56.7 years (13.3); 50% female]. Of these, 21 with asthma reported that their condition was stable/well controlled and 13 with COPD felt their condition was manageable. Most participants found FF/VI easy to use (asthma, 25; COPD, 23), easy to integrate into their daily routine (asthma, 25; COPD, 24), and able to control symptoms for ≥?24 h (asthma, 14; COPD, 16). During the survey phase, 199 individuals were recruited [asthma, n?=?100; COPD, n?=?99; mean age (SD) 63.6 years (15.1); 59.3% female]. Most participants were satisfied/very satisfied with the efficacy of FF/VI in terms of all-day symptom relief (asthma, 84%; COPD, 75%) and found FF/VI easy/very easy to fit into their daily routine (asthma, 99%; COPD, 96%), easy/very easy to use (asthma, 97%; COPD, 92%), and convenient/very convenient to take as instructed (asthma, 95%; COPD, 93%). Significantly more individuals with asthma (87% versus 46%, P?<?0.001) and numerically more individuals with COPD (84% versus 76%, P?=?0.055) were satisfied/very satisfied with FF/VI compared with their most recent previous maintenance medication.

Conclusion

The majority of individuals in this study had confidence in FF/VI and were satisfied or very satisfied with various key attributes of the treatment.

Trial Registration

GSK study HO-15-15503/204888.

Funding

GSK.

     

Efficacy and Safety of Aclidinium/Formoterol versus Tiotropium in COPD: Results of an Indirect Treatment Comparison

Introduction

The objective of this study was to estimate the relative efficacy and safety of fixed-dose combination aclidinium/formoterol 400/12 μg twice daily compared to tiotropium 18 μg once daily in adult patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).

Methods

A systematic literature review performed in March 2014, using a predefined search strategy in MEDLINE, EMBASE and Cochrane Library, identified 17 randomized placebo-controlled trials, (tiotropium n = 15; aclidinium/formoterol n = 2). Outcomes of interest were: bronchodilation (peak and trough forced expiratory volume in 1 s (FEV₁)), COPD symptoms [Transition Dyspnea Index (TDI) focal score and % of responders (>1 unit improvement)] and Health Related Quality of Life (HRQoL) [St. George’s Respiratory Questionnaire (SGRQ) total score and % responders (>4 unit improvement)], % of patients with ≥1 exacerbations, adverse events (AE), serious adverse events (SAE), hospitalization and mortality, all at 24 weeks. In the absence of head-to-head trials between aclidinium/formoterol and tiotropium, a Bayesian indirect treatment comparison (ITC) was used with placebo as common control.

Results

Regarding bronchodilation, aclidinium/formoterol was found to be more efficacious than tiotropium at peak FEV₁, with mean difference in change from baseline (DCFB) 143 mL [95% credible interval (CrI): 112, 174] and at trough FEV₁ [DCFB 26 mL (95% CrI ?2, 55)]. Aclidinium/formoterol is expected to be more efficacious than tiotropium in improving dyspnea symptoms measured by TDI [DCFB 0.54 points (95% CrI 0.09, 0.99); odds ratio (OR) of responders 1.51 (95% CrI 1.11, 2.06)]. SGRQ results are comparable for aclidinium/formoterol versus tiotropium [DCFB ?0.52 (95% CrI ?2.21, 1.17); OR of responders 1.16 (95% CrI 0.47, 2.87)]. The ITC results suggest similar safety profiles regarding AEs, SAEs and hospitalization.

Conclusion

Based on the ITC, aclidinium/formoterol is expected to be more efficacious than tiotropium in terms of lung function and symptom control while providing comparable HRQoL results and safety profile.

Funding

AstraZeneca.

     

Cost-Effectiveness of Ranibizumab Versus Aflibercept for Macular Edema Secondary to Branch Retinal Vein Occlusion: A UK Healthcare Perspective

Introduction

Ranibizumab and aflibercept are anti-vascular endothelial growth factor agents licensed for the treatment of visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). The aim of this study was to estimate, from a UK healthcare payer’s perspective, the cost-effectiveness of ranibizumab versus aflibercept in this indication.

Methods

A Markov model was used to simulate the outcomes and costs of treating BRVO. Patient baseline characteristics and efficacy data for ranibizumab were obtained from the BRAVO trial. The relative efficacy of aflibercept was derived from a published network meta-analysis. Injection frequencies were derived from ranibizumab and aflibercept studies included in the network meta-analysis. Health states were defined by increments of 10 letters in best corrected visual acuity (BCVA). Patients could gain or lose a maximum of two health states between cycles. The first cycle was 6 months, followed by monthly cycles. Different utility values were assigned to the better-seeing and worse-seeing eyes based on BCVA. A 2-year treatment time frame and a lifetime time horizon were used. Future costs and health outcomes were discounted at 3.5% per annum. Sensitivity analyses were used to test the robustness of the model.

Results

The lifetime cost per patient treated was £15,273 with ranibizumab and £17,347 with aflibercept. Ranibizumab was dominant over aflibercept, producing incremental health gains of 0.0120 quality-adjusted life-years (QALYs) and cost savings of £2074. Net monetary benefit for ranibizumab at a willingness-to-pay threshold of £20,000/QALY was £2314. Sensitivity analyses showed that the results were robust to variations in model parameters.

Conclusions

Ranibizumab provides greater health gains at a lower overall cost than aflibercept in the treatment of visual impairment due to macular edema secondary to BRVO. Ranibizumab is therefore cost-effective from a UK healthcare payer’s perspective.

Funding

Novartis Pharma AG, Basel, Switzerland

     

Evaluation of the Efficiency of Single-Inhaler Combination Therapy with Budesonide/Formoterol Fumarate in Patients with Bronchial Asthma in Daily Clinical Practice

Introduction

The effectiveness of single-inhaler budesonide/formoterol fumarate combination therapy for asthma has been previously shown for the original product. The aim of this nonrandomized, open-label, postauthorization efficacy study (PAES) real-life clinical assessment was to evaluate the clinical effectiveness of a second product (Bufomix Easyhaler^®) in the daily clinical practice of asthma therapy.

Methods

This multicenter PAES was conducted by 220 unselected allergologists and pulmonologists who enrolled 2200 adult outpatients (age 49.8 ± 17.9 years) with asthma treated with Bufomix Easyhaler^® for at least 14 days before enrolment. Asthma control was assessed during three subsequent visits with 8–12-week intervals on the basis of the Asthma Control Test (ACT). Adherence was assessed with the Medication Adherence Questionnaire. In addition, patient satisfaction with Bufomix Easyhaler^® was scored, and adverse drug reactions were recorded.

Results

The percentage of patients with well-controlled asthma or total control of asthma (ACT score 20-25 points) increased from 46.6% at the first visit to 90.8% at the third visit (p < 0.001). In addition, the percentage of patients with poor control of asthma (ACT score less than 15 points) decreased from 14.9% to 1.2% (p < 0.001). The adherence rate increased from 88% at the first visit to 95.3% at the third visit. Patient satisfaction with the use of this dry powder inhaler increased with the duration of its use. Only one adverse drug reaction was reported.

Conclusion

The results obtained confirm the effectiveness of Bufomix Easyhaler^® in the treatment of asthma in outpatient adults in daily clinical practice.

Funding

Orion Corporation

     

Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study

Introduction

We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β₂-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD.

Methods

This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV₁) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy. Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa. The primary end point was the change from baseline in trough FEV₁ at week 8 with a noninferiority margin of ? 50 mL in the per-protocol (PP) population. The incidence of adverse events was also assessed.

Results

In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population. UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV₁ at week 8 [FEV₁ change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28–77 mL); p < 0.001]. Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV₁ at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34–3.14). Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.

Conclusion

In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV₁ at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD. Both treatments had similar safety profiles. These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.

Trial Registration

ClinicalTrials.gov identifier NCT02799784.

Funding

GlaxoSmithKline.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Assessing Short-term Deterioration in Maintenance-naïve Patients with COPD Receiving Umeclidinium/Vilanterol and Tiotropium: A Pooled Analysis of Three Randomized Trials

Introduction

Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy. The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.

Methods

This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747). Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis. The primary endpoint was trough forced expiratory volume in 1 s (FEV₁). St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV₁, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.

Results

UMEC/VI improved trough FEV₁ versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102–189) and ITT: 95 ml (71–118); both P < 0.001]. Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO. UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51–0.85); ITT: 0.62 (0.54–0.71), both P ≤ 0.001]. Adverse events were similar across both populations and treatments.

Conclusions

Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD. Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115). Funding: This study was funded by GSK.

     

Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis Patients in the United States

Introduction

The prevalence of endometriosis and the need for treatment in the USA has led to the need to explore the contemporary cost burden associated with the disease. This retrospective cohort study compared direct and indirect healthcare costs in patients with endometriosis to a control group without endometriosis.

Methods

Women aged 18–49 years with endometriosis (date of initial diagnosis = index date) were identified in the Truven Health MarketScan^® Commercial database between 2010 and 2014 and female control patients without endometriosis were matched by age and index year. The following outcomes were compared: healthcare resource utilization (HRU) during the 12-month pre- and post-index periods (including inpatient admissions, pharmacy claims, emergency room visits, physician office visits, and obstetrics/gynecology visits), annual direct (medical and pharmacy) and indirect (absenteeism, short-term disability, and long-term disability) healthcare costs during the 12-month post-index period (in 2014 US$). Multivariate analyses were conducted to estimate annual total direct and indirect costs, controlling for demographics, pre-index clinical characteristics, and pre-index healthcare costs.

Results

Overall, 113,506 endometriosis patients and 927,599 controls were included. Endometriosis patients had significantly higher HRU during both the pre- and post-index periods compared to controls (p < 0.0001, all categories of HRU). Approximately two-thirds of endometriosis patients underwent an endometriosis-related surgical procedure (including laparotomy, laparoscopy, hysterectomy, oophorectomy, and other excision/ablation procedures) in the first 12 months post-index. Mean annual total adjusted direct costs per endometriosis patient during the 12-month post-index period was over three times higher than that for a non-endometriosis control [$16,573 (standard deviation (SD) = $21,336) vs. $4733 (SD = $14,833); p < 0.005]. On average, incremental direct and indirect 12-month costs per endometriosis patient were $10,002 and $2132 compared to their matched controls (p < 0.005).

Conclusions

Endometriosis patients incurred significantly higher direct and indirect healthcare costs than non-endometriosis patients.

Funding

AbbVie Inc.

     

Examining the Impact of Rehospitalization on Healthcare Cost of Myocardial Infarction Patients in Beijing: A Retrospective Observational Study

Introduction

To examine the impact of rehospitalization on the healthcare expenditure of myocardial infarction (MI) patients in Beijing.

Methods

Retrospective data of MI patients were retrieved from the Beijing Medical Insurance Database, an administrative database of social medical reimbursement activities for the urban population in Beijing, China. Ten percent of patients diagnosed with MI from January 1 to December 31, 2012 were randomly selected and their first hospitalization was considered as the index event. Their hospital utilization after the index event was extracted till September 30, 2013. Rehospitalization was defined as an event of hospital admission due to the same diagnosis and with a time interval of at least 14 days from the most recent admission. The healthcare cost of patients was analyzed, including inpatient cost and outpatient cost. Patients’ demographic characteristics, co-morbidities, and length of hospital stay were also collected from the database.

Results

Of the 1235 MI patients identified, 335 (mean age of 66.14 ± 15.04 years; 84.18% males) had rehospitalization. The rate of MI recurrence was 27.13%. The annual healthcare expense was significantly higher for MI patients with rehospitalization compared to MI patients without rehospitalization (99,920.43 ± 84,113.52 CNY vs. 58,877.89 ± 93,942.90 CNY; P < 0.001). The significant positive predictors of incurring healthcare expenditure were male gender, age 45 years old or more, length of stay at first hospital admission, whether having rehospitalization (yes/no), co-morbidity (heart failure and diabetes), and admission to a tertiary hospital at first hospital admission.

Conclusion

There was a high risk of MI recurrence for patients in Beijing. The annual healthcare cost of MI patients with rehospitalization was significantly higher than MI patients without rehospitalization. Male patients of 45 years old or more with heart failure and diabetes are likely to incur higher healthcare expenditure.

     

Changes in Healthcare Spending After Diagnosis of Comorbidities Among Endometriosis Patients: A Difference-in-Differences Analysis

Introduction

We sought to characterize changes in healthcare spending associated with the onset of 22 endometriosis-related comorbidities.

Methods

Women aged 18–49 years with endometriosis (N = 180,278) were extracted from 2006–2015 de-identified Clinformatics^® DataMart claims data. For 22 comorbidities, comorbidity patients were identified on the basis of having a first comorbidity diagnosis after their initial endometriosis diagnosis. Controls were identified on the basis of having no comorbidity diagnosis and were matched 1:1 to comorbidity patients on demographics and baseline spending. Total medical and pharmacy spending was measured during 12 months before and after each patient’s index date (first comorbidity diagnosis for comorbidity patients, and equal number of days after earliest endometriosis claim for controls). Pre–post spending differences were compared using difference-in-differences linear regression. Total and comorbidity-related cumulative spending per patient for all endometriosis patients were calculated annually for the 5 years following endometriosis diagnosis.

Results

The number of endometriosis patients with each comorbidity varied between 121 for endometrial cancer and 16,177 for fatigue. Healthcare spending increased significantly with the onset of eight comorbidities: breast cancer, ovarian cancer, pregnancy complications, systemic lupus erythematosus/rheumatoid arthritis/Sjogren’s/multiple sclerosis, infertility, uterine fibroids, ovarian cyst, and headache [p < 0.001 except for headache (p = 0.045)]. Spending decreased significantly for fatigue, cystitis/UTI, and eczema [p < 0.001 except for fatigue (p = 0.048)] and was not statistically different for the other 11 comorbidities. Difference-in-differences estimates were significantly higher for comorbidity patients for all comorbidities except eczema (p ≤ 0.003). Mean 5-year total cumulative spending was $58,191 per endometriosis patient, of which between 11% and 23% was attributable to comorbidity-related medical claims.

Conclusion

For all but one of the 22 comorbidities associated with endometriosis, comorbidity onset was associated with a relative increase in total healthcare spending.

Funding

AbbVie Inc.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Hypoglycemia After Initiation of Basal Insulin in Patients with Type 2 Diabetes in the United States: Implications for Treatment Discontinuation and Healthcare Costs and Utilization

Introduction

Hypoglycemia and fear of hypoglycemia may contribute to basal insulin discontinuation, poor glycemic control, and increased healthcare burden in patients with type 2 diabetes (T2D). This study aimed to determine the impact of hypoglycemia soon after basal insulin initiation on treatment discontinuation and economic outcomes in patients with T2D.

Methods

Hypoglycemic events within 6 months of basal insulin initiation were identified using retrospective cohort data from patients with T2D, at least 18 years of age, initiated on basal insulin therapy in the Clinformatics? Data Mart for Multiplan claims database from January 1, 2008, through August 31, 2012. Data were adjusted for baseline characteristics. Discontinuation was established for patients with 12-month follow-up data, while discontinuation risk was assessed in the extended analysis (6- to 24-month follow-up) by Cox regression analysis. Healthcare use and costs were determined.

Results

Of 55,608 patients, 4.5% experienced hypoglycemia within 6 months of basal insulin initiation. Patients with hypoglycemia were more likely to discontinue basal insulin within 12 months of initiation (79.0% vs. 74.2%; P < 0.001). Data, adjusted for baseline characteristics such as age, any baseline hypoglycemia, and use of oral antidiabetes drugs, showed that patients with hypoglycemia had a greater risk of discontinuation (hazard ratio 1.16; 95% confidence interval 1.03, 1.32; P = 0.0164), were more likely to have a hospitalization (41.0% vs. 24.3%; P < 0.001) or an ED visit (55.8% vs. 35.1%; P < 0.001), and had higher diabetes-related ($13,662 vs. $7506; P < 0.001) and all-cause ($30,719 vs. $19,079; P < 0.001) healthcare costs.

Conclusions

US patients with T2D who experienced hypoglycemia within 6 months of basal insulin initiation were more likely to discontinue treatment, accompanied by a greater healthcare burden.

Funding

Sanofi US, Inc.

     

Health Self-Efficacy Among Populations with Multiple Chronic Conditions: the Value of Patient-Centered Communication

Introduction

Using cross-sectional survey data, we assessed the association between chronic illness burden and health-related self-efficacy, evaluating whether patient-centered communication is associated with self-efficacy and if that relationship varies by chronic illness burden.

Methods

Data were from the Health Information National Trends Survey, a cross-sectional survey of the US adult population collected in 2012–2013 (n = 3630). Health-related self-efficacy was measured with the item: “Overall, how confident are you about your ability to take good care of your health?” and the prevalence of six chronic conditions and depression/anxiety was assessed. Patient-centered communication was measured as the frequency with which respondents perceived their healthcare providers allowed them to ask questions, gave attention to their emotions, involved them in decisions, made sure they understood how to take care of their health, helped them to deal with uncertainty, and if they felt they could rely on their healthcare providers to take care of their healthcare needs.

Results

Health-related self-efficacy was significantly lower among individuals with greater illness burden. In adjusted analysis, individuals who experienced more positive patient-centered communication reported higher levels of self-efficacy (β = 0.26, P < 0.0001); this association was strongest among those with greater illness burden.

Conclusion

Higher levels of self-efficacy were observed among patients reporting more positive patient-centered communication; the observed association was stronger among those with greater chronic illness burden.

     

An economic evaluation of budesonide/formoterol for maintenance and reliever treatment in asthma in general practice

Introduction

In budesonide/formoterol (Symbicort® Turbuhaler®, AstraZeneca, Lund, Sweden) maintenance and reliever therapy (SMART), patients with asthma take a daily maintenance dose of budesonide/formoterol, with the option of taking additional doses for symptom relief instead of a short-acting β₂-agonist (SABA). This study assesses the cost-effectiveness of SMART compared with usual care in patients with mild-to-moderate persistent asthma treated by general practitioners in the Netherlands from a societal perspective.

Methods

The study was linked to a randomized, active-controlled, open-label, multicenter, 12-month clinical trial, with a prospective collection of resource use. One hundred and two patients ≥18 years with mild-to-moderate persistent asthma and daily inhaled corticosteroids (ICS) prior to the trial were included. SMART was given as two inhalations of budesonide/formoterol (100/6 μg) once daily, plus additional doses as needed. The control group was treated according to guidelines, which prescribe medium daily doses of ICS plus an SABA if needed. A long-acting β₂-agonist (LABA) is added if necessary. Effectiveness was measured as the proportion of asthma-control days, Asthma Control Questionnaire (ACQ) scores, the net proportion of patients with relevant ACQ improvement, and the proportion of well-controlled patients. Costs included asthma medication, physician contacts, and absence from work.

Results

Mean total costs for SMART were €134.81 lower (95% CI: ?€439.48; €44.85). Production losses were €94.10 (95% CI: ?€300.60; €0.29) lower for SMART (€10.77 vs. €104.87). No significant differences in health outcomes were seen, with 3.81 fewer asthma-control days per patient-year for SMART (95% CI: ?36.8; 30.8), a 0.049 better ACQ score (95% CI: ?0.21; 0.29), a 5.8% larger net proportion of improved patients (95% CI: t15.6%; 27.3%), and a 2.1% (95% CI: ?25.5; 20.8%) smaller increase in the proportion of well-controlled patients.

Conclusions

Treating primary care patients with mild-to-moderate persistent asthma with SMART instead of ICS plus bronchodilators does not affect health outcomes and does not increase costs; therefore, is likely to be an alternative for guideline-directed treatment, from a health and economic perspective.

     

Secukinumab is Efficacious and Safe in Hispanic Patients with Moderate-to-Severe Plaque Psoriasis: Pooled Analysis of Four Phase 3 Trials

Introduction

There is little evidence available on the efficacy and safety of biologic therapies for the treatment of psoriasis in Hispanic patients. Secukinumab is demonstrated to be highly effective for clearing psoriasis. The aim of this study was to compare the efficacy and safety of secukinumab in Hispanic and non-Hispanic patients.

Methods

Data were pooled from four phase 3 studies of secukinumab in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic were included in the Hispanic subgroup.

Results

Efficacy responses (Psoriasis Area and Severity Index [PASI] 75/90/100 and Investigator’s Global Assessment 2011 modified version 0/1) for secukinumab 300 mg were greater than for etanercept at week 12 in the Hispanic and non-Hispanic patient subgroups. At week 12 with secukinumab 300 mg, PASI 90/100 responses were achieved by 70.6%/35.9% of Hispanic patients and 58.0%/28.1% of non-Hispanic patients. At week 12 with secukinumab 150 mg, PASI 90/100 responses were achieved by 59.5%/25.1% of Hispanic patients and 41.2%/13.4% of non-Hispanic patients. In both subgroups, peak efficacy responses with secukinumab were observed at week 16 and were maintained to week 52.

Conclusions

Secukinumab is highly effective for clearing psoriasis in both Hispanic and non-Hispanic patients.

Funding

Novartis Pharmaceutical Corporation.

     

Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(?) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(?) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

     

Patients’ Perspective of Medication Adherence in Chronic Conditions: A Qualitative Study

Introduction

About 50% of patients do not take their long-term therapy for chronic conditions as prescribed. Many studies have centered on patients’ adherence to a specific treatment or single conditions, but few have taken all chronic conditions into consideration from a patient’s perspective. This study aims to explore factors that impact on drug compliance and to identify strategies to improve this from the perspective of patients with at least one chronic condition.

Methods

Patients were recruited by healthcare professionals from a hospital pharmacy, four community pharmacies, patient associations, and a primary care center in Barcelona. Five focus groups were conducted (N = 36). Conversations were audiotaped and transcribed verbatim to allow qualitative analysis.

Results

Study subjects were aged 39–90 years (mean 65 years) and the mean number of comorbidities per patient was 2.3 (range 1–7). The main modifiers of therapeutic conduct were: patients’ health beliefs, patient–prescriber relationships, and patients’ motivation and perception of illness control. Study participants wanted greater participation in decision-making concerning their health and increased education about their illness and medication. They also wanted individualized healthcare that took their preferences and personal and emotional issues into account.

Conclusion

Our results highlight how the patient–prescriber’s relationship and factors such as health beliefs, motivation and perception of illness control impact on medication adherence in chronic patients. Future interventions to optimize adherence to treatment should focus on shared decision-making and more extensive health education.

Funding

Celgene Corporation.