Systematic Literature Review to Assess Prevalence of Gina-Defined Segments of Asthma and Phenotypes

VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6

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PRS3 Feasibility of Matching-Adjusted Indirect Comparison (MAIC) of Omalizumab (OMA) vs. Mepolizumab (Mepo) in Moderate-to-Severe Asthma

study suggested that a majority of patients who switched to budesonide/formoterol Spiromax Stayed on this therapy. Further longitudinal observations might be supportive to this conclusion.

Ayyagari R1, Álvares L2, Mu F1, Hacking V3, Martinez R2, Signorovitch JE1 1Analysis Group, Inc., Boston, MA, USA, 2Novartis Pharma AG, Basel, Switzerland, 3Novartis Pharmaceuticals UK Ltd, Surrey, UK

PRS6 Burden of Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome (ACOS)

Objectives: The relative efficacy of OMA to MEPO for asthma patients has not been studied in randomized clinical trials (RCTs). Naïve indirect comparisons (ICs) are invalid due to differences between trials. The feasibility of an IC using MAIC is unknown. This study aims to assess feasibility of a MAIC of efficacy of OMA vs. MEPO.  Methods: 4 OMA RCTs included in a systematic review (Norman et al. 2013) and 3 published MEPO RCTs were screened for comparability. The pivotal phase 3 trials in Europe, INNOVATE (Humbert et al, 2005; OMA vs. placebo; n= 419) and MENSA (Ortega et al, 2014; MEPO vs. placebo; n= 385), were selected. Patient data from INNOVATE were adjusted using MAIC for differences in baseline characteristics (age, sex, body mass index, smoking history, asthma duration, oral glucocorticoid use, pre-bronchodilation forced expiratory volume in 1 second (FEV1), % predicted FEV1, FEV1:forced vital capacity, morning peak expiratory flow, immunoglobulin E, blood eosinophils, and severe exacerbations in the previous year). Matching feasibility was assessed using effective sample size.  Results: Main differences between INNOVATE vs MENSA included: population (allergic asthmatics vs. asthmatics with high serum eosinophilia); clinically significant exacerbation definition; inhaled glucocorticoid use; trial time period (2001-2004 vs. 2012-2014). After MAIC, the effective sample size for estimating active vs. placebo effects was only 25 patients (active, n= 14 and placebo, n= 11).  Conclusions: Differences between INNOVATE and MENSA resulted in too small an effective sample size to compare efficacy of OMA vs MEPO. Alternative approaches should be explored. PRS4 Comparative Efficacy of Reslizumab and Mepolizumab For The Treatment of Asthma: A Network Meta-Analysis Sharma R1, Cheung A1, Bolzani A1, Barakat S2, Sun SX3, Tarasova O2, Druyts E1, FitzGerald JM4 1Precision Health Economics, Vancouver, BC, Canada, 2Teva Canada Innovation, Montreal, QC, Canada, 3Teva Pharmaceuticals, Malvern, PA, USA, 4University of British Columbia, Vancouver, BC, Canada

Objectives: Reslizumab and mepolizumab have been developed to target severe eosinophilic asthma phenotypes. In the absence of head-to-head comparisons, a network meta-analysis (NMA) was conducted to assess the relative efficacy of reslizumab 3.0 mg/kg compared to mepolizumab (100 mg, fixed dose, subcutaneous injection).  Methods: A systematic literature review was conducted to identify randomised controlled trials (RCTs) assessing the efficacy and safety of reslizumab and mepolizumab in patients with moderate-to-severe inadequately controlled asthma. The RCT results were synthesized using NMAs for exacerbation rates, and time to first exacerbation, analysed at end of study, and change in eosinophil count and forced expiratory volume in one second (FEV1, litres), analysed at various timepoints. All analyses were performed in a Bayesian framework.  Results: Eleven RCTs were included. Early responder (week 16) analysis in the moderate-to-severe asthma population revealed statistical improvements with reslizumab for change in eosinophil counts compared to mepolizumab (MD: -173.51 cells/µl, 95%CrI: -262.97 to -84.62) and best supportive care, BSC (MD: -362.16 cells/µl, 95%CrI: -399.92 to -325.04). Reslizumab was also statistically advantageous to BSC in reducing the rate of severe exacerbations (RR: 0.45; 95%CrI: 0.28-0.71). Time to first exacerbation was significantly prolonged with reslizumab compared to BSC (hazard ratio: 0.54; 95%CrI: 0.44-0.66). Among severe asthmatic patients, reslizumab was comparable to mepolizumab in reducing the rate of severe exacerbations (risk ratio, RR: 0.74, 95%CrI: 0.561.01) and statistically advantageous in improving FEV1 (4-week mean difference, MD: 0.16, 95%CrI: 0.03-0.28).  Conclusions: Reslizumab appears to be a suitable alternative to mepolizumab in treating patients with moderate-to-severe asthma. PRS5 Real-Life Persistence of Budesonide/Formoterol Spiromax for The Management of Asthma and COPD in The UK Benhaddi H1, Van Der Tol M2, Price D3, Batsiou M4, Ariely R5 1TEVA Pharma, Brussels, Belgium, 2TEVA Pharma, Amsterdam, The Netherlands, 3Research In Real Life, Singapore, Singapore, 4Research In Real Life, Cambridge, UK, 5TEVA Pharma, Malvern, PA, USA

Objectives: Asthma and chronic obstructive pulmonary disease (COPD) are major respiratory diseases with high morbidity, mortality and socio-economic costs. Budesonide/formoterol Spiromax is indicated for the management of asthma and COPD. This study measured the extent to which patients who switched to budesonide/formoterol Spiromax remained on this therapy. The aim of this study is to evaluate the persistence of change in patients switching to budesonide/formoterol Spiromax from other licensed inhaled corticosteroid (ICS) / long-acting β 2 agonist (LABA) fixed-dose combinations (FDC)  Methods: Retrospective database study of Asthma and COPD patients treated with ICS/LABA FDC during 1 year and switching to budesonide/formoterol Spiromax. Data was extracted from the Optimum Patient Care Research Database (OPCRD) which comprises anonymised data from 500+ clinical practices in the UK. Persistence of change to budesonide/formoterol Spiromax was defined as percentage of patients switching to budesonide/formoterol Spiromax and with no prescription for ICS/LABA FDC in the 6 months following. A change-back rate of < 17% was assumed to indicate acceptibility of the switch to budesonide/ formoterol Spiromax.  Results: Overall, 181 patients were included. 90.6% were on Symbicort Turbuhaler® and 4.4%, 3%, and 1.7% were on Evohaler®, Accuhaler® and Fostair® respectively during the baseline period prior to switching to budesonide/ formoterol Spiromax. Only 17 (9.4%) patients had ≥ 1 prescription for other ICS/LABA FDC after initiation with budesonide/formoterol Spiromax during the follow-up period which was lower than the “change-back” rate of 17%.  Conclusions: This

Pathak P1, Gruenberger J2, Vuppala B1, Yadav V1, Ghosh S1, Gupta S1 1Novartis, Hyderabad, India, 2Novartis, Basel, Switzerland

Objectives: Coexistence of Asthma and Chronic Obstructive Pulmonary Disease is defined as overlap syndrome. Large variations have been observed in the published prevalence estimates of ACOS due to ambiguity in the disease definitions. The aim of this systematic review and meta-analysis was to update the prevalence estimate of ACOS and analyze trends in epidemiology, and the associated economic and humanistic burden (Alshabanat et al., 2015).  Methods: Literature published in MEDLINE and EMBASE were searched up to May 2016 to identify studies reporting data in epidemiology, healthcare resource utilization, associated costs, and health-related quality-of-life for patients with ACOS. Random effects metaanalysis was performed to pool the prevalence of ACOS in COPD patients using R software. Data was compared between the overlap-syndrome and COPD-only group.  Results: Twenty-six studies were included in this systematic review. The overall pooled prevalence of ACOS among COPD patients was 27% (95% CI: 16%–38%) and 23% (95% CI: 15%–31%) in the population and hospital-based studies, respectively. Hospitalization rates were more than double in the ACOS group compared to COPD-only group. Patients with ACOS also had more frequent emergency room visits, higher healthcare costs, and lower health-related quality of life compared to patients with COPD. However, conflicting results were observed with respect to mortality with several studies reporting lower mortality rates in the ACOS group than the COPD-only group.  Conclusions: This review reiterates that there is a substantial economic and humanistic burden associated with ACOS. It is important to mention though, since there are no confirmed criteria for diagnosing ACOS, studies using different criteria were included in this analysis. PRS7 Systematic Literature Review to Assess Prevalence of Gina-Defined Segments of Asthma and Phenotypes Shah A1, Gala S1, Nanavaty M1, Narayanan S2, Mwamburi M1 1Market Access Solutions LLC, Raritan, NJ, USA, 2Market Access Solutions, LLC, Potomac, MD, USA

Objectives: Asthma is a complex, heterogeneous disease that can be subdivided into numerous overlapping phenotypes or segments on the basis of clinical, patho-physiological, and inflammatory markers. Novel treatments including biologics have targeted immunologic phenotypes within moderate-severe asthma. Lack of consistency in definitions of severity and control status among studies reporting the prevalence of various segments presents challenges. We reviewed publications reporting prevalence of asthma segments based on the definitions of control and severity using Global INitiative for Asthma guidelines (GINA) to understand the prevalence of the heterogeneous segments of asthma and to identify gaps.  Methods: A systematic review was conducted in PubMed and Embase to identify publications reporting prevalence of severe (GINA step 4 and 5) or moderate (GINA step 3) asthma populations and GINA asthma control (i.e. controlled, partially controlled or uncontrolled). Search was limited to studies in the English, between 1999 and 2016, and assessing adults and/or adolescents.  Results: Of 405 titles and abstracts screened, nine studies were included in the analysis with eight studies from Europe, one from Nigeria, and none from the Americas. Majority of patients (66%-84%) with uncontrolled asthma were severe across Europe and Nigeria. In a study in Germany in allergic asthma, 13% were severe (19% of whom were uncontrolled) and 29% were moderate (4% uncontrolled). In Italy, 43% of Asthma-COPD Overlap Syndrome (ACOS) had uncontrolled asthma. In Spain, the prevalence of severe, uncontrolled asthma was 4% of all asthmatics.  Conclusions: Moderatesevere uncontrolled asthma represent the highest clinical and economic burden and unmet needs. Literature reporting prevalence of asthma segments is sparse with inconsistent definitions and a denominators. Robust real-world data analyses are needed to determine and define phenotypes and respective overlaps empirically to aid in mapping opportunities, unmet needs, designing trials, establishing care pathways, and defining payer and pricing policies.

PRS8 Prevalence of Severe Asthma and Poorly Controlled Severe Asthma During 2009–2013 in The Netherlands Smits E1, Overbeek JA1, Valgardsson VS2, Van Laer J3, Penning-van Beest F1 1PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands, 2Janssen-Cilag AS, Oslo, Norway, 3Janssen Pharmaceutica N.V., Beerse, Belgium

Objectives: Asthma is a major health problem and patients with (poorly controlled) severe asthma are at high risk of exacerbations, hospitalization and death. Furthermore, they often have severely impaired quality of life. Literature regarding the prevalence of severe asthma and poorly controlled severe asthma is scarce and unknown for the Netherlands. Objective is to determine the prevalence of severe asthma and poorly controlled severe asthma over time, using healthcare databases in the Netherlands.  Methods: A cross-sectional study was performed, using data from the PHARMO Database Network, a population-based network in the Netherlands combining data from different healthcare settings such as outpatient pharmacies, general practitioners (GP) and hospitals. Prevalences of asthma, severe asthma and poorly controlled severe asthma were determined among adult patients between 2009 and 2013. Patients with a GP recorded diagnosis of asthma were included. (Poorly controlled) severe asthma was based on an algorithm including asthma medication and/or exacerbations.  Results: The source population