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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.

Genome-wide association studies (GWAS) have identified hundreds of genetic susceptibility loci for cancers and other complex diseases. However, the public health and clinical relevance of these discoveries is unclear. Evaluating the combined associations of genetic and environmental risk factors, particularly those that can be modified, will be critical in assessing the utility of genetic information for risk stratified prevention. In this commentary, using breast cancer as a model, we show that genetic information in combination with other risk factors can provide levels of risk stratification that could be useful for individual decision-making or population-based prevention programs. Our projections are theoretical and rely on a number of assumptions, including multiplicative models for the combined associations of the different risk factors, which need confirmation. Thus, analyses of epidemiological studies with high-quality risk factor information, as well as prevention trials, are needed to empirically assess the impact of genetics in risk stratified prevention.

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.

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.

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).

IntroductionOverdiagnosis of breast cancer due to mammography screening, defined as the diagnosis of screen-detected cancers that would not have presented clinically in a women's lifetime in the absence of screening, has emerged as a highly contentious issue, as harm caused may question the benefit of mammographic screening. Most studies included women over 50 years old and little information is available for younger women.MethodsWe estimated the overdiagnosis of breast cancer due to screening in women aged 40 to 49 years using data from a randomised trial of annual mammographic screening starting at age 40 conducted in the UK. A six-state Markov model was constructed to estimate the sensitivity of mammography for invasive and in situ breast cancer and the screen-detectable mean sojourn time for non-progressive in situ, progressive in situ, and invasive breast cancer. Then, a 10-state simulation model of cancer progression, screening, and death, was developed to estimate overdiagnosis attributable to screening.ResultsThe sensitivity of mammography for invasive and in situ breast cancers was 90% (95% CI, 72 to 99) and 82% (43 to 99), respectively. The screen-detectable mean sojourn time of preclinical non-progressive and progressive in situ cancers was 1.3 (0.4 to 3.4) and 0.11 (0.05 to 0.19) years, respectively, and 0.8 years (0.6 to 1.2) for preclinical invasive breast cancer. The proportion of screen-detected in situ cancers that were non-progressive was 55% (25 to 77) for the first and 40% (22 to 60) for subsequent screens. In our main analysis, overdiagnosis was estimated as 0.7% of screen-detected cancers. A sensitivity analysis, covering a wide range of alternative scenarios, yielded a range of 0.5% to 2.9%.ConclusionAlthough a high proportion of screen-detected in situ cancers were non-progressive, a majority of these would have presented clinically in the absence of screening. The extent of overdiagnosis due to screening in women aged 40 to 49 was small. Results also suggest annual screening is most suitable for women aged 40 to 49 in the United Kingdom due to short cancer sojourn times.

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