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Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma. SS frequently spreads to other locations, referred to as metastatic SS (mSS) and is associated with a high death rate. Patients treated with first-line chemotherapy (1L setting), may need further lines of treatment (≥2L setting), which commonly involve the drugs pazopanib and trabectedin. This study assessed how well pazopanib and trabectedin work in people with ≥2L mSS, by examining both clinical trial (CT) and real-world (RW) studies. Overall, findings across 16 studies showed that mSS patients lived approximately 10 months after treatment with pazopanib or trabectedin in the ≥2L setting, and this was similar across both agents (10.3 months for pazopanib; 10.4 months for trabectedin) and between the CT (10.8 months) and the RW (9.9 months) settings. In terms of response to treatment, a higher percentage of people appeared to respond in RW settings (17.7%) than in CTs (9.5%), and to pazopanib (18.9%) compared with trabectedin (12.3%). These results show there is a need for better treatments for patients with previously treated mSS. These findings are useful benchmarks for the development of future treatment approaches for this rare disease.

Andrea Gabrio,1 Necdet B Gunsoy,2 Gianluca Baio,1 Alan Martin,3 Victoria F Paly,4 Nancy Risebrough,5 David MG Halpin,6 Dave Singh,7 Robert A Wise,8 MeiLan K Han,9 Fernando J Martinez,10 Gerard J Criner,11 Neil Martin,12 David A Lipson,13,14 Afisi S Ismaila15,16 1UCL Statistical Science, University College London, London, UK; 2Value Evidence & Outcomes, GlaxoSmithKline, Brentford, UK; 3Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UK; 4Global HTA, Health Economics, Reimbursement & Outcomes, ICON Plc., Philadelphia, PA, USA; 5Global HTA, Health Economics, Reimbursement & Outcomes, ICON plc., Toronto, ON, Canada; 6University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 7The Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 8The Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 9University of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, USA; 10Joan and Sandy Weill Department of Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA; 11Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; 12Global Medical Affairs, GlaxoSmithKline, Uxbridge, UK; 13Development Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 14Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 15Value Evidence and Outcomes, GlaxoSmithKline, Collegeville, PA, USA; 16Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Afisi S Ismaila, Value Evidence and Outcomes, GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, PA, 19426-0989, USA, Tel +19199320430; +19193158229, Email afisi.s.ismaila@gsk.comAbstract: Objectives: In the IMPACT trial (NCT02164513), triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) showed clinical benefit compared with dual therapy with either FF/VI or UMEC/VI in the treatment of chronic obstructive pulmonary disease (COPD). We used data from IMPACT to determine whether this translated into differences in COPD-related healthcare resource utilization (HRU) costs in a United Kingdom (UK) setting.Methods: In a within-trial analysis, individual patient data from the IMPACT intention-to-treat (ITT) population were analyzed to estimate rates of COPD-related HRU with FF/UMEC/VI, FF/VI, or UMEC/VI. A Bayesian approach was applied to address issues typically encountered with this kind of data, namely data missing due to early study withdrawal, subjects with zero reported HRU, and skewness. Rates of HRU were estimated under alternate assumptions of data being missing at random (MAR) or missing not at random (MNAR). UK-specific unit costs were then applied to estimated HRU rates to calculate treatment-specific costs.Results: Under each MNAR scenario, per patient per year (PPPY) rates of COPD-related HRU were lowest amongst those patients who received treatment with FF/UMEC/VI compared with those receiving either FF/VI or UMEC/VI. Although absolute HRU rates and costs were typically higher for all treatment groups under MNAR scenarios versus MAR, final economic conclusions were robust to patient withdrawals.Conclusions: PPPY rates were typically lower with FF/UMEC/VI versus FF/VI or UMEC/VI.Keywords: single-inhaler triple therapy, COPD, healthcare resource use, cost

Patients with severe eosinophilic asthma experience daily activity limitations and reduced productivity at work. Using anonymized individual patient-level data from two previously conducted randomized, double-blind, placebo-controlled studies (MENSA [GSK ID:115588/NCT01691521]; MUSCA [GSK ID:200862/NCT02281318]), we investigated the effect of mepolizumab on work productivity, activity limitation, symptoms, and rescue medication use. Patient-reported outcomes including Work Productivity and Activity Impairment-General Health (WPAI-GH) scores (impairment percentages, 0%-100%), global activity limitation (scale 1-4), and perceived change in activity limitation (Likert scale 1-7) since the start of the study were analyzed. WPAI-GH scores from MENSA were analyzed post hoc for employed patients using mixed model repeated measures; global activity limitation and perceived change in activity limitation from MUSCA were analyzed by ordinal logistic regression. Mean changes from baseline in daily asthma symptom scores (scale 0-5) and rescue medication use (occasions/day) were also assessed, via a post hoc meta-analysis of MENSA and MUSCA. At study end, WPAI-GH scores indicative of overall work impairment, impairment while working, and activity impairment consistently improved with mepolizumab versus placebo. Overall, 76% versus 54% of patients rated their activity as "much better," "better," or "slightly better" since the start of the study with mepolizumab versus placebo. Mepolizumab was associated with numerically larger improvements from baseline in asthma symptoms (treatment difference 0.21-0.29 points) and rescue medication use (treatment difference -0.08 to -0.22 occasions/day) versus placebo. Our results indicate that patients with severe eosinophilic asthma may experience improved activity limitation, work productivity, symptoms, and rescue medication use with mepolizumab.

Background A wide range of therapeutic regimens, including single-inhaler triple therapies (SITTs), are now available for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Thus, an improved understanding of patient preferences may be valuable to inform physician prescribing decisions. This study was performed to assess the factors considered by patients when making decisions about their COPD treatments using qualitative techniques. Methods In the United Kingdom, United States and Germany, individual qualitative interviews (n=10 per country) and focus groups (1 per country; [United Kingdom, n=4; United States, n=6; Germany, n=6 participants]) were conducted. Interviews and focus groups were semi‑structured, lasting approximately 60 minutes, and focused on treatment preferences. Data were analyzed according to emerging themes identified from the interviews; qualitative thematic analysis of the data was performed using specialist software. Results In interviews and focus groups, efficacy, ease of use, and lower frequency of use were favored attributes for current treatment, while side effects, medication taste, and more complex administration techniques were key dislikes. In interviews, most participants would consider a switch in medication, mainly for improved efficacy, but also to reduce medication frequency or following physician advice. Overall, efficacy and ease of use were the 2 most important attributes reported in interviews in all 3 countries. Conclusion Patients with COPD have preferences for certain attributes of medication, highlighting the multi-faceted nature of treatment effectiveness and the importance of the delivery device.These results were subsequently used to inform the design of a discrete choice experiment.

Objective: To assess the effect of asthma exacerbations and mepolizumab treatment on health status of patients with severe asthma using the St George’s Respiratory Questionnaire (SGRQ).Meth...

Victoria Federico Paly,1 Ian Naya,2 Necdet B Gunsoy,3 Maurice T Driessen,4 Nancy Risebrough,5 Andrew Briggs,6 Afisi S Ismaila7,81ICON Health Economics, ICON, Philadelphia, PA, USA; 2Global Respiratory Franchise, GSK, Brentford, Middlesex, UK; 3Value Evidence and Outcomes, GSK, Uxbridge, Middlesex, UK; 4Value Evidence & Outcomes, GSK, Brentford, Middlesex, UK; 5ICON Health Economics, ICON, Toronto, ON, Canada; 6Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; 7Value Evidence & Outcomes, GSK, Collegeville, PA, USA; 8Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaPurpose: Clinically important deterioration (CID) in chronic obstructive pulmonary disease (COPD) is a novel composite endpoint that assesses disease stability. The association between short-term CID and future economic and quality of life (QoL) outcomes has not been previously assessed. This analysis considers 3-year data from the TOwards a Revolution in COPD Health (TORCH) study, to examine this question.Patients and methods: This post hoc analysis of TORCH (NCT00268216) compared costs and utilities at 3years among patients without CID (CID-) and with CID (CID+) at 24weeks. A positive CID status was defined as either: a deterioration in forced expiratory volume in 1 second (FEV1) of ≥100 mL from baseline; or a ≥4-unit increase from baseline in St George’s Respiratory Questionnaire (SGRQ) total score; or the incidence of a moderate/severe exacerbation. Patients from all treatment arms were included. Utility change was based on the EQ-5D utility index. Costs were based on healthcare resource utilization from 24weeks to end of follow-up combined with unit costs for the UK (2016 GBP), and reported as per patient per year (PPPY). Adjusted estimates were generated controlling for baseline characteristics, treatment assignment, and number of CID criteria met.Results: Overall, 3,769 patients completed the study and were included in the analysis (stable CID- patients, n=1,832; unstable CID+ patients, n=1,937). At the end of follow-up, CID- patients had higher mean (95% confidence interval [CI]) utility scores than CID+ patients (0.752 [0.738, 0.765] vs 0.697 [0.685, 0.71]; difference +0.054; P

Hannah B Lewis,1 Melanie Schroeder,2 Necdet B Gunsoy,3 Ellen M Janssen,4 Samuel Llewellyn,5 Helen A Doll,1 Paul W Jones,6 Afisi S Ismaila7,8 1Patient Centred Outcomes, ICON plc., London, UK; 2Value Evidence and Outcomes, GlaxoSmithKline plc., Brentford, UK; 3Value Evidence and Outcomes, GlaxoSmithKline plc., Uxbridge, UK; 4Patient Centred Outcomes, ICON plc., Gaithersburg, MD, USA; 5Patient Centred Outcomes, ICON plc., Abingdon, UK; 6Respiratory Therapy Area, GlaxoSmithKline plc., Brentford, UK; 7Value Evidence and Outcomes, GlaxoSmithKline plc., Collegeville, PA, USA; 8Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Afisi S IsmailaValue Evidence and Outcomes, GlaxoSmithKline plc., 1250 South Collegeville Road, Collegeville, PA 19426-0989, USATel +1 919 932 0430Email afisi.s.ismaila@gsk.comIntroduction: With increasing availability of different treatments for chronic obstructive pulmonary disease (COPD), we sought to understand patient preferences for COPD treatment in the UK, USA, and Germany using a discrete choice experiment (DCE).Methods: Qualitative research identified six attributes associated with COPD maintenance treatments: ease of inhaler use, exacerbation frequency, frequency of inhaler use, number of different inhalers used, side effect frequency, and out-of-pocket costs. A DCE using these attributes, with three levels each, was designed and tested through cognitive interviews and piloting. It comprised 18 choice sets, selected using a D-efficient experimental design. Demographics and disease history were collected and the final DCE survey was completed online by participants recruited from panels in the UK, USA and Germany. Responses were analyzed using mixed logit models, with results expressed as odds ratios (ORs).Results: Overall, 450 participants (150 per country) completed the DCE; most (UK and Germany, 97.3%; USA, 98.0%) were included in the final analysis. Based on relative attribute importance, avoidance of side effects was found to be most important (UK: OR 11.65; USA: OR 7.17; Germany: OR 11.45; all p< 0.0001), followed by the likelihood of fewer exacerbations (UK: OR 2.22; USA: OR 1.63; Germany: OR 2.54; all p< 0.0001) and increased ease of use (UK: OR 1.84; USA: OR 1.84; Germany: OR 1.60; all p< 0.0001). Number of inhalers, out-of-pocket costs, and frequency of inhaler use were found to be less important. Preferences were relatively consistent across the three countries. All participants required a reduction in exacerbations to accept more frequent inhaler use or use of more inhalers.Conclusion: When selecting COPD treatment, individuals assigned the highest value to the avoidance of side effects, experiencing fewer exacerbations, and ease of inhaler use. Ensuring that patients’ preferences are considered may encourage treatment compliance.Keywords: discrete choice experiment, DCE, symptomatic chronic obstructive pulmonary disease, COPD, stated-preference methods

Severe asthma (SA) can be uncontrolled despite guideline-directed treatment. We described SA characteristics and identified factors associated with uncontrolled disease and frequent exacerbations. Post hoc analysis of the observational IDEAL study (201722/NCT02293265) included patients with SA aged ≥12 years receiving high-dose inhaled corticosteroids plus additional controller(s) for ≥12 months. Uncontrolled SA was defined by Asthma Control Questionnaire (ACQ)-5 scores ≥1.5 or ≥1 exacerbations (prior year), and further stratified by exacerbation frequency (no/infrequent [0–1] vs frequent [≥2]; prior year); associated factors were determined using multivariate logistic regression. Of 670 patients with SA, 540 (81%) were uncontrolled (ACQ-5 scores ≥1.5: 80%; ≥1 exacerbations [prior year]: 71%). Uncontrolled patients had lower lung function and worse health-related quality of life (HRQoL) than controlled patients; 197/540 (37%) experienced frequent exacerbations (prior year). Worse St George’s Respiratory Questionnaire (SGRQ) total score, comorbid sinusitis, or eczema were significantly associated with uncontrolled SA; younger age, never smoker status, exacerbation requiring hospitalization (previous year), worse SGRQ symptom score, comorbid nasal polyps, COPD, or osteoporosis were significantly associated with uncontrolled SA with frequent exacerbations. In IDEAL, one-fifth of patients with SA were controlled, based on symptoms. Uncontrolled, exacerbating SA was associated with specific comorbidities, frequent exacerbations, a lower lung function, and compromised HRQoL, although inference from this analysis is limited by the selective cross-sectional nature of the cohort. Nonetheless, these data highlight the need for more effective precision treatments in this population.

Introduction Previous studies showed that mepolizumab significantly reduces exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma. However, early studies reported inconsistent effects on lung function. This study specifically assessed the onset of clinical effect and the relationship of baseline blood eosinophil count of mepolizumab 100 mg subcutaneous (SC) administration on morning peak expiratory flow (AM PEF). Methods Post hoc analysis of data from two randomized, double-blind, placebo-controlled studies (MENSA, NCT01691521; MUSCA, NCT02281318) of 4-weekly mepolizumab 100 mg versus placebo in patients with severe eosinophilic asthma. Individual study results were generated using a mixed model repeated measures model controlling for multiple covariates and were combined using a fixed effects meta-analysis via inverse-variance weighting. Results Significant improvements in AM PEF after the first dose of mepolizumab 100 mg SC vs. placebo were seen as early as week 1 and continued to improve further with subsequent doses. The mean change in AM PEF was 26 L/min in the mepolizumab group compared to 4 L/min in the placebo group, p

Background: Pazopanib (P) and trabectedin (T) are approved targeted treatments for metastatic soft tissue sarcoma (mSTS). Our objective was to evaluate the efficacy (from clinical trials [CT]) and effectiveness (from real-world studies [RW]) of P and T in second line (2L+) mSS. Methods: This meta-analysis included all English language studies assessing P or T efficacy/effectiveness in patients with 2L+ mSS, 1999 onwards, identified by a systematic literature review. Outcomes were overall response rate (ORR) representing the proportion of patients who have achieved CR or PR during the study and median overall survival (mOS) in months (mos) from start of study medication. Proportions from studies were pooled using generalized linear mixed models to account for small sample sizes, zero events and random site effects. Medians were combined using the weighted median of the medians method with 95% confidence intervals from an inverted sign test. Results: 16 studies with 405 patients with 2L+ mSS met the inclusion criteria. Response was measured variably across studies (CT: RECIST v1.0, v1.1; RW: modified RECIST or clinician assessment). ORR estimates were higher in RW than CTs (Table). OS results were consistent across CTs and RW (Table). Conclusions: This is the first study to provide estimates for patients with mSS in the 2L+ setting, distinct from mSTS and pool outcomes of targeted therapies. RW estimates of ORR for both treatments were higher than those observed in trials likely due to variable definition of response and in underlying prognostic factors. mOS was consistent across both types of studies and was similar to mOS seen on placebo (10.7 mos in PALETTE study) suggesting a high unmet need in this population. Funding: GSK (213368). Outcomes with pazopanib (P) and trabectedin (T) in clinical trials (CT) and real-world (RW) studiesPTP & T pooledORR-ALL (%)N=6, n=96, 18.9 (8.5, 41.8)N=7, n=162, 12.3 (8.0, 18.9)N=13, n=258, 14.7 (9.2, 23.4)ORR-CT (%)N=1, n=38, 13.2 (2.4, 23.9)†N=3, n=57, 7.0 (2.7, 18.1)N=4, n=95, 9.5 (5.1, 17.6)ORR-RW (%)N=5, n=58, 20.2 (7.4, 54.8)N=4, n=105, 15.2 (9.7, 23.9)N=9, n=163, 17.7 (9.9, 31.5)mOS-ALL (mos)N=4, n=96, 10.3 (8.7, 13.8)N=4, n=165, 9.9 (1.5, 13.9)N=8, n=261, 9.9 (9.2, 13.9)mOS-CT (mos)ND*ND*N=3, n=113, 10.3 (8.7, 13.9)mOS-RW (mos)ND*ND*N=5, n=148, 9.9 (9.2, 13.9)*Not done due to small sample size; †results of study since N=1. N=number of studies; n=number of patients. Estimates presented with 95% confidence intervals. Citation Format: Charlotte Carroll, Nashita Patel, Necdet B. Gunsoy, Dan Parks, Heide A. Stirnadel-Farrant, Shibani Pokras. Meta-analysis of pazopanib and trabectedin in 2L+ metastatic synovial sarcoma (2L+ mSS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2630.

Objectives: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice. Methods: This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible. Results: The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31–41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (n = 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7–21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (n = 101), 27–37% were omalizumab-eligible and 18% were reslizumab-eligible. Conclusions: Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma.

Background Severe asthma is a heterogeneous disease. Patients with both eosinophilic and allergic asthma phenotypes may be eligible for treatment with mepolizumab and omalizumab. Evidence on the relative effectiveness of these treatments in this ‘overlap’ population would be informative for clinical and payer decision making. Methods A systematic literature review and indirect treatment comparison (Bayesian framework) were performed to assess the comparative effectiveness and tolerability of mepolizumab and omalizumab, as add-ons to standard of care. Studies included in the primary analysis were double-blind, randomized controlled trials, ≥12 weeks' duration enrolling patients with severe asthma with a documented exacerbation history and receiving high-dose inhaled corticosteroids plus ≥1 additional controller. Two populations were examined: patients potentially eligible for 1) both treatments (Overlap population) and 2) either treatment (Trial population). Results In the Overlap population, no differences between treatments in clinically significant exacerbations and exacerbations requiring hospitalization were found, although trends favored mepolizumab (rate ratio [RR]:0.66 [95% credible intervals (Crl):0.37,1.19]; 0.19[0.02,2.32], respectively). In the Trial population, mepolizumab treatment produced greater reductions in clinically significant exacerbations (RR:0.63 [95% CrI:0.45,0.89]) but not exacerbations requiring hospitalization compared with omalizumab (RR:0.58 [95% Crl: 0.16,2.13]), although the trend favored mepolizumab. Both treatments had broadly comparable effects on lung function, and similar tolerability profiles. Conclusions Whilst this analysis has limitations due to a restricted evidence base and residual heterogeneity, it showed that in patients with severe asthma, mepolizumab seems to be at least as effective as omalizumab and that the tolerability profiles of the two treatments did not meaningfully differentiate.

Background: Mepolizumab (mepo) is an approved add-on treatment for adults with severe refractory eosinophilic asthma (SEA). Objective: To describe the real-world population of patients (pts) with SEA receiving mepo. Methods: REALITI-A is a prospective, observational, multi-country cohort study using integrated data capture methods (eCRFs, claims data, phone app). Study aims to recruit ~1,050pts with asthma, prescribed mepo 100mg SC in a clinical practice setting. Reimbursement criteria vary by country and often include the following: blood eosinophil counts (BEC; ≥150 [baseline] and/or ≥300 [prior yr] cells/µL) and 2–4 exacerbations [prior yr] or maintenance oral corticosteroid (mOCS) use. Primary objective: to compare clinically significant exacerbations (CSE; requiring OCS and/or ED visit/hospitalisation) pre-/post-mepo use. Baseline characteristics from eCRF of the initial pts are shown here. Results: By 30 Sept 2017, 170pts were enrolled (Table). Of the 137pts with a BEC, 89.8% had counts ≥150 cells/µL at baseline (Geo mean [SD log]: 436 (1.2) cells/µL) and ≥75% had ≥300 cells/µL (prior yr). In total, 85.2% and 56.1% of pts had ≥2 and ≥4 CSE in the prior yr, respectively, and 56.1% of pts had mOCS use. Conclusions: The real-world vs clinical trial population of pts with SEA receiving mepo have more frequent exacerbations in the past yr and higher BEC. This might be driven by reimbursement criteria. Funding: GSK [204710]

Purpose With new single-inhaler triple therapies available for treatment of COPD, understanding patient preferences can be used to inform physicians’ prescribing decisions and improving patient care. A discrete choice experiment (DCE) was conducted in the UK, Germany and USA. This abstract presents results from the UK only. Methods Following qualitative research in patients with COPD, attributes describing features of COPD maintenance treatments were identified: ease of inhaler use (with an increasing number of mistakes to reduced efficacy/worsening of symptoms), number of exacerbations in the next year, daily frequency of inhaler use, number of different inhalers used and side-effects. The online DCE survey comprised 18 choice sets with logical (dominant) choice and consistency checks, along with demographic and disease history questions. Cognitive debriefing interviews and a pilot study confirmed the feasibility of the survey. The final DCE survey was completed by 150 patients in the UK. Responses to the DCE were analysed using mixed-effect logit models. Results Of the 150 UK respondents, 146 (97.3%) answered the logical choice check correctly and were included in the final models; 119 (79.3%) selected the same choice within the consistency check. The odds ratios (ORs) for the majority of attributes were >1.0 and statistically significant, showing that for each unit benefit in the attribute (e.g., lower daily medication frequency, lower frequency of side effects), there is an increased likelihood of patients preferring the treatment (see table 1). The strongest drivers of treatment choice were relief of exacerbations (OR=2.22 for each unit reduction) and reduction of side effects (OR=4.59 for some and 11.65 for no side effects versus a lot of side effects). Conclusions This study suggests that, in principle, patients in the UK with COPD place most importance on the reduction of symptoms and avoidance of side effects when choosing a treatment. However, inhaler number, ease and frequency of use were also important drivers of choice. Patient inhaler preference is important to consider when selecting COPD treatment as preference for an inhaler may improve treatment compliance. Funding GSK study 2 06 455 (HO-16–16285); ICON received funding from GSK to conduct the study only.

Introduction: Clinically important deterioration (CID) in COPD is a measure of meaningful short-term worsening in lung function, health status or a first acute exacerbation. The economic and quality of life (QoL) impact of avoiding CID is unclear. This analysis of data from the 3-year TOwards a Revolution in COPD Health (TORCH) study examined this question. Methods: This post hoc analysis of TORCH (NCT00268216) compared annual costs and QoL in unstable patients with any CID (CID+) vs stable CID-free patients (CID-). CID+ status in any treatment arm in the first 6 months was defined as: ≥100 mL decline in FEV1 or ≥4-unit deterioration in SGRQ total score from baseline or a first moderate/severe exacerbation. Costs were calculated based on healthcare resource use captured from 6 months to study end, applying UK NHS unit costs. QoL was measured using the EQ-5D utility index. Adjusted values, controlled for baseline characteristics, treatment assignment and CID status, are presented. Results: Following study completion, 3769 and 1989 patients contributed to the 3-year cost and QoL analysis, respectively. Significantly lower annual costs/patient and higher utility scores were seen for CID- vs CID+ patients (Figure). Conclusions: Maintaining COPD stability and avoiding short-term CID may be associated with year-on-year cost savings and better preservation of QoL. Funding: GSK (HO-16-16345)

Background: Acute exacerbations have a significant and permanent impact on lung function and quality of life (QoL) in patients with COPD. Previous studies focused on lung function in COPD; studies exploring the impact of exacerbations in patients with severe COPD are needed. Objective: This post-hoc meta-analysis explored the impact of exacerbations on lung function and QoL using data from two phase 3 mepolizumab RCTs in severe COPD patients with an eosinophilic phenotype and receiving inhaled glucocorticoid-based triple therapy. Methods: Pre-bronchodilator FEV1, Saint George’s Respiratory Questionnaire (SGRQ), and Euroqol-5D (EQ-5D) measures were analysed using a random intercept-slope model with a time-varying covariate for exacerbations experienced during the trials. The impact of exacerbations was estimated per moderate (requiring systemic glucocorticoid and/or antibiotic treatment) and severe exacerbation (leading to hospitalization or death) event. Results: COPD exacerbations were associated with a statistically significant worsening in SGRQ score and EQ-5D utility index, with higher impact associated with severe exacerbations (Figure 1). Moderate and severe exacerbations had a similar impact on FEV1. Conclusions: Moderate and severe exacerbations have significant impact on QoL in severe COPD patients. In patients with more severe COPD, exacerbations are a strong indicator of worsening in disease status and QoL. Funding: GSK [HO-17-18342]

Three anti-IL-5 pathway-directed therapies are approved for use in patients with severe eosinophilic asthma (SEA); however, no head-to-head comparison data are available.We sought to compare the efficacy of licensed doses of mepolizumab, benralizumab, and reslizumab in patients with SEA, according to baseline blood eosinophil counts.This indirect treatment comparison (ITC) used data from a Cochrane review and independent searches. Eligible studies were randomized controlled trials in patients aged 12 years or greater with SEA. End points included annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire score and FEVEleven studies were included. All treatments significantly reduced the rate of clinically significant exacerbations and improved asthma control versus placebo in all blood eosinophil count subgroups. Mepolizumab reduced clinically significant exacerbations by 34% to 45% versus benralizumab across subgroups (rate ratio ≥400 cells/μL: 0.55 [95% CI, 0.35-0.87]; ≥300 cells/μL: 0.61 [95% CI, 0.37-0.99]; and ≥150 cells/μL: 0.66 [95% CI, 0.49-0.89]; all P .05) and by 45% versus reslizumab in the 400 cells/μL or greater subgroup (rate ratio, 0.55 [95% CI, 0.36-0.85]; P = .007). Asthma control was significantly improved with mepolizumab versus benralizumab (all subgroups: P .05) and versus reslizumab in the 400 cells/μL or greater subgroup (P = .004). Benralizumab significantly improved lung function versus reslizumab in the 400 cells/μL or greater subgroup (P = .025).This ITC of the licensed doses suggests that mepolizumab was associated with significantly greater improvements in clinically significant exacerbations and asthma control compared with reslizumab or benralizumab in patients with similar blood eosinophil counts.

Background Mepolizumab significantly reduces exacerbations in patients with severe eosinophilic asthma. The early identification of patients likely to receive long-term benefit from treatment could ensure effective resource allocation. Objective To assess potential continuation rules for mepolizumab in addition to initiation criteria defined as 2 or more exacerbations in the previous year and blood eosinophil counts of 150 cells/mL or more at initiation or 300 cells/mL or more in the previous year. Methods This post hoc analysis included data from 2 randomized, double-blind, placebo-controlled studies (NCT01000506 and NCT01691521) of mepolizumab in patients with severe eosinophilic asthma (N [ 1,192). Rules based on blood eosinophils, physician-rated response to treatment, FEV1, Asthma Control Questionnaire (ACQ-5) score, and exacerbation reduction were assessed at week 16. To assess these rules, 2 key metrics accounting for the effects observed in the placebo arm were developed. Results Patients not meeting continuation rules based on physician-rated response, FEV1, and the ACQ-5 score still derived long-term benefit from mepolizumab. Nearly all patients failing to reduce blood eosinophils had counts of 150 cells/mL or less at baseline. For exacerbations, assessment after 16 weeks was potentially premature for predicting future exacerbations. Conclusion There was no evidence of a reliable physician-rated response, ACQ-5 score, or lung functionebased continuation rule. The added value of changes in blood eosinophils at week 16 over baseline was marginal. Initiation criteria for mepolizumab treatment provide the best method for assessing patient benefit from mepolizumab treatment, and treatment continuation should be reviewed on the basis of a predefined reduction in long-term exacerbation frequency and/or oral corticosteroid dose.

Introduction Severe asthma patients have limited therapeutic options. These patients remain at risk of exacerbations, their quality of life is negatively impacted and they place a significant burden on the health service. Mepolizumab is licensed for use in patients with severe eosinophilic asthma. As reimbursement authorities expect evidence of health economic benefits, this study aimed to estimate the cost-utility of mepolizumab as an add-on therapy to standard of care (SOC) versus SOC alone. Methods A de novo Markov cost-utility model was produced which compared the costs and outcomes of mepolizumab vs. SOC over a lifetime horizon. Primary analysis was based on data from the MENSA clinical trial (NCT01691521). Patients entering the model were assigned to mepolizumab or SOC and experienced treatment-specific probabilities of exacerbation events with an associated risk of mortality and disutility. The model included a continuation criteria where patients on mepolizumab who failed to demonstrate an exacerbation reduction were transitioned to the SOC arm. Costs and health outcomes were discounted annually at 3.5%. The model did not account for indirect costs or value in steroid reduction. Results In the basecase analysis (patients with ≥300 eosinophil cells/µL and ≥4 exacerbations in the previous 12 months) the incremental cost-effectiveness ratio (ICER) of add-on mepolizumab compared with SOC was £30,268/QALY gained. Scenario analyses showed that the ICER was sensitive to the starting age of the cohort, the source of utility and asthma-related mortality. Conclusion Mepolizumab represents a clinically efficacious and cost-effective alternative to SOC.

Rationale: Mepolizumab (Mepo) is indicated as add-on therapy for patients with severe asthma and is effective at reducing exacerbations. This post-hoc analysis aims to quantify the impact of Mepo on Work Productivity and Activity Impairment – General Health (WPAI-GH) in two clinical trials (MENSA, SIRIUS). Methods: The WPAI-GH questionnaire is a validated instrument and was administered at baseline and each 4-weekly visit. Responses were analysed using mixed model repeated measures. Results: 50% (MENSA, 285/576) and 49% (SIRIUS, 66/135) of patients were employed at baseline. Employed patients were younger and more likely to be male compared to unemployed patients, but had similar asthma disease characteristics. Mepo treatment improved WPAI-GH versus placebo patients receiving optimized standard of care (Figure 1). Conclusions: Mepo had a considerable beneficial impact on work and activity impairment in both studies; however, differences in SIRIUS and %work time missed due to health in MENSA were not significant, likely due to small number of patients in SIRIUS and few work hours reported as missed in MENSA. These results suggest that Mepo may have indirect cost benefits to employers and society by allowing patients to increase productivity. Funding: GSK [115588/NCT01691521 & 115575/NCT01691508]

Rationale: Patients with severe asthma experience substantial impact on health related quality of life. Characterization of predictors of worse health status in severe asthma may help identify patients requiring additional interventions. This post-hoc analysis of the IDEAL study (201722; NCT02293265) evaluated predictors of respiratory health status, measured by the St George9s Respiratory Questionnaire (SGRQ). Methods: The IDEAL study was a cross-sectional, non-interventional study in 6 countries, and included subjects ≥12 years with severe asthma (ATS/ERS guidelines) treated with high-dose ICS plus additional controller(s) for ≥12 months. Assessments included a blood sample, spirometry, and PRO, including the SGRQ. Clinical and demographic characteristics predictive of SGRQ score in the total cohort were evaluated with univariate analysis and multivariate linear regression. Results: In univariate analysis, predictors of SGRQ included gender, pre-bronchodilator FEV 1 %predicted, bronchodilator reversibility, smoking status, use of maintenance oral corticosteroids (OCS), history of clinically significant exacerbations (prior 12 months), and blood eosinophil level. Total IgE and use of omalizumab were not associated with SGRQ. In multivariate regression, predictors of lower health status score included history of clinically significant exacerbations, lower FEV 1 %predicted, OCS use, female gender, and current or a history of smoking. Conclusions: Among patients with severe asthma, there are clinical and demographic characteristics associated with an impact on respiratory health status measured by the SGRQ, that could be addressed by targeted intervention. Funding: GSK (NCT02293265).

The IDEAL study described the eligibility for biologic asthma treatment according to label criteria (omalizumab) or study protocols (mepolizumab, reslizumab). Methods: Post-hoc analysis of EU subjects from a cross-sectional, single-visit, observational study enrolling subjects aged ≥12 yrs with severe asthma (SA) (ATS/ERS guidelines: ≥12months high-dose ICS+ additional controller(s) treatment). Eligibility defined as: Mepolizumab: ≥2 exacerbations (corticosteroid and/or ED visit and/or hospitalization in prior 12M) and blood eosinophil ≥150 cells/µl at Visit 1 or historically ≥300cells/µl; Omalizumab: (EU1) ≥1 exacerbation in prior 12M, allergic asthma, FEV 1 ≤80% pred., meeting weight and IgE criteria or (EU2) as EU1 except ≥2 exacerbation and ACQ≥1.5; Reslizumab: ≥1 exacerbation, ACQ≥1.5, airway reversibility ≥12% and blood eosinophil ≥400cells/µl at Visit 1. Results: Of 292 SA patients recruited from France, Germany, and UK, 233 (80%) were included after exclusion of current omalizumab users. Of these, 56 subjects (24%) were eligible for mepolizumab; 50 (22%) and 29 (12%) for omalizumab EU1 and EU2 criteria, respectively; and 16 subjects (7%) for reslizumab. Among the 56 mepolizumab-eligible subjects, 22 (39%) and 20 (36%) were also eligible for omalizumab by EU1 or EU2 criteria and 12 (21.4%) eligible for reslizumab. Conclusions: In this EU-based severe asthma population not currently taking omalizumab, approximately 1/4 are mepolizumab-eligible (i.e., uncontrolled; with eosinophilic inflammation). In those mepolizumab eligible, about one third may also be eligible for omalizumab, showing that the available biologics mostly serve different SA populations. (Funded by GSK; 201722).

Introduction: Despite careful design of dose ranging studies, full characterisation of dose-response for clinical endpoints is not always achieved. The absence of a dose-response for reduction in clinically significant exacerbations with mepolizumab in the primary analysis led to a meta-analysis using individualized weight-based measures of dose. Objectives: Evaluate weight-based measures of mepolizumab dose-response for reduction in annualized exacerbation rate. Methods: Inclusion of exacerbation data with dose and bodyweight information from two GSK funded mepolizumab severe asthma pivotal studies (DREAM and MENSA). Intravenous doses were converted to subcutaneous-equivalent dose using absolute bioavailability of 80 and 70% and normalized by individual bodyweight, body mass index and body surface area at baseline. Results: Description of the dose-response showed that although the maximal treatment effect was well-estimated, location of half-maximal efficacious dose (ED 50 ) was poor. Using a Bayesian analysis with informative priors for ED 50 (away from the pharmacological ED 50 (blood eosinophil reduction) [11 mg]), convergence was achieved. Posterior ED 50 distributions showed a shift in prior belief towards the pharmacological ED 50 with narrower credibility interval. The largest effects were noted for bodyweight-adjusted dose-response. Conclusions: Exacerbation data from studies DREAM and MENSA did not show a dose-response by conventional analysis unlike with Bayesian analysis which also showed consistency between the efficacy dose-response and the well-defined dose-response for pharmacology, with an ED 50 of approximately 0.17 mg/kg (12 mg).

Objectives: Describe demographic and clinical traits among patients with severe asthma (SA) and a subset of patients with inadequately controlled severe eosinophilic asthma (SEA). Methods: IDEAL study (201722; NCT02293265) is a cross-sectional cohort of SA patients (age ≥12 years, high-dose ICS + additional controller/s for ≥12 months) recruited from specialist clinics in 6 countries. Inadequately controlled SEA was defined as (1) blood eosinophil count of ≥300 cells/μL in the past 12 months prior to study visit OR ≥150 cells/μL at study visit AND (2) ≥2 or more severe exacerbations of asthma (requiring systemic corticosteroid and/or emergency room (ER) visit and/or hospitalization) in the past 12 months. Extensive medical history supplemented with existing medical records and a blood sample were collected. Results: The cohort consisted of 670 SA patients, of whom 137 (20%) had SEA. Compared to the total SA cohort, the subset with SEA had equal proportion of females (62%), was slightly younger (mean: 48 vs. 51 yrs) and had more significant smoking history (45% vs. 36%). Mean of severe exacerbations was 3.2 vs. 1.2/patient-year and 23% vs 9% had ≥1 asthma hospitalization, with more frequent regular OCS use (20% vs. 14%). Further, higher levels of IgE (179 vs. 155 KU/L), lower FEV 1 values (64 vs. 68 FEV 1 % pred.) and more frequent comorbidities were observed. Conclusions: The IDEAL study shows a considerable disease burden in a cohort of patients with severe asthma, with impaired lung function and on average more than one exacerbation/yr. The subset with inadequately controlled severe eosinophilic asthma with more than 3 exacerbations/yr seems to drive much of this disease burden. Funded by GSK.

Background Findings from previous studies showed that mepolizumab significantly reduces the rate of exacerbations in patients with severe eosinophilic asthma. To assess the relationship between baseline blood eosinophil counts and efficacy of mepolizumab we did a secondary analysis of data from two studies, stratifying patients by different baseline blood eosinophil thresholds. Methods We did a post-hoc analysis of data, which was completed on Sept 25, 2015, from two randomised, double-blind, placebo-controlled studies of at least 32 weeks duration (NCT01000506 [DREAM] and NCT01691521 [MENSA]) done between 2009 and 2014. In these studies, mepolizumab (DREAM: 75 mg, 250 mg, or 750 mg intravenously; MENSA: 75 mg intravenously or 100 mg subcutaneously) versus placebo was given at 4-week intervals in addition to standard care (high-dose inhaled corticosteroids plus ≥1 additional controller with or without daily oral corticosteroids) to patients aged 12 years or older with a clinical diagnosis of asthma, a history of at least two exacerbations in the previous year that required systemic corticosteroid treatment, and evidence of eosinophilic airway inflammation. The primary endpoint in both studies was the annual rate of clinically significant exacerbations (defined as worsening of asthma that required the use of systemic corticosteroids, or admission to hospital, or an emergency-room visit, or a combination of these occurrences). In our analysis, the primary outcome was the annualised rate of exacerbations in patients stratified by baseline eosinophil counts (≥150 cells per μL, ≥300 cells per μL, ≥400 cells per μL, and ≥500 cells per μL) and baseline blood eosinophil ranges ( Findings Of 1192 patients, 846 received mepolizumab and 346 received placebo. The overall rate of mean exacerbations per person per year was reduced from 1·91 with placebo to 1·01 with mepolizumab (47% reduction; rate ratio [RR] 0·53, 95% CI 0·44–0·62; p Interpretation Our analysis has shown a close relationship between baseline blood eosinophil count and clinical efficacy of mepolizumab in patients with severe eosinophilic asthma and a history of exacerbations. We noted clinically relevant reductions in exacerbation frequency in patients with a count of 150 cells per μL or more at baseline. The use of this baseline biomarker will help to select patients who are likely to achieve important asthma outcomes with mepolizumab.

Background: Studies show that mepolizumab can reduce the frequency of clinically significant exacerbations in patients with severe eosinophilic asthma, compared with placebo. However, important events such as hospitalizations and emergency room visits are rare and difficult to characterize in single studies. Objective: We sought to compare hospitalization or hospitalization and/or emergency room visit rates in patients with severe eosinophilic asthma treated with mepolizumab or placebo in addition to standard of care for at least 24 weeks. Methods: This study was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. PubMed and the GSK Clinical Study Register were searched for suitable studies. The primary end points were the rate of exacerbations requiring hospitalization and the rate of exacerbations requiring hospitalization/emergency room visit. The proportion of patients with 1 or more event was also assessed. All mepolizumab doses were combined and individual patient-level data were analyzed. Results: Four studies (n = 1388) were eligible for inclusion. Mepolizumab significantly reduced the rate of exacerbations requiring hospitalization (relative rate, 0.49; 95% CI, 0.30-0.80; P = .004) and hospitalization/emergency room visit (relative rate, 0.49; 95% CI, 0.33-0.73; P < .001) versus placebo. Significant reductions of 45% and 38% were also observed for the proportion of patients experiencing 1 or more hospitalization and hospitalization and/or emergency room visit, respectively. Conclusions: Mepolizumab approximately halved exacerbations requiring hospitalization and/or emergency room visits compared with placebo in patients with severe eosinophilic asthma. This treatment addresses a key outcome in a patient population with a high unmet need (GSK Study 204664).

Background: Limited data describe the association between the frequency of asthma exacerbations and the decline in lung function in severe asthma. Objective: To determine whether asthma exacerbations are associated with enhanced decline in lung function. Methods: Changes in lung function were analyzed retrospectively using data from the DREAM and MENSA studies of mepolizumab intervention in patients with severe asthma. Patients were either nonsmokers or former smokers. A linear regression model was used to analyze the relationship between the number of exacerbations and decline in FEV1 across treatment groups. Results: In a combined post hoc analysis, 57% (n = 572) of patients had no exacerbations and experienced an improvement in postbronchodilator FEV1 of 143 mL. In contrast, in patients who experienced 3 or more exacerbations, there was a decrease in postbronchodilator FEV1 of 77 mL in the combined analysis. The linear modeling analysis estimated that for each exacerbation seen during the observational period, there was a decrease of 50 mL in FEV1 (P < .001). Conclusions: A direct relationship between the number of exacerbations in patients with severe eosinophilic asthma and decline in lung function was observed. Repeated exacerbations may be associated with accelerated loss of lung function.