Rachael DiSantostefano

Risk of pneumonia with inhaled corticosteroid/long-acting β2 agonist therapy in chronic obstructive pulmonary disease: a cluster analysis

Background Pneumonia poses a significant risk in patients with moderate to severe chronic obstructive pulmonary disease but data are limited on the disease phenotypes most susceptible to pneumonia. Methods Cluster analysis using a data-driven recursive partitioning algorithm was employed using baseline data from two pooled one-year randomized exacerbation trials (n=3,255) of fluticasone furoate/vilanterol or vilanterol alone to identify distinct patient groups at greatest risk of pneumonia or serious (hospitalization or death) pneumonia. Results Five clusters were identified. Patients at greater risk of first pneumonia had more severe obstruction (forced expiratory volume in one second/forced vital capacity <46%) and either a body mass index <19 kg/m2 (hazard ratio 7.8, 95% confidence interval 4.7–13.0; n=144) or a pneumonia history and greater comorbidities (hazard ratio 4.8, 95% confidence interval 3.0–7.7; n=374) relative to the cluster with the lowest pneumonia risk (reference; n=1310). Multiple comorbidities and use of psychoanaleptics also contributed to an increased risk of pneumonia in more obstructed patients. Independent of cluster, use of inhaled corticosteroids was associated with pneumonia (hazard ratio 1.89, 95% confidence interval 1.25–2.84) and serious pneumonia (hazard ratio 2.92, 95% confidence interval 1.40–6.01). Conclusion Cluster analysis can identify patient populations at risk for serious safety outcomes and inform risk management strategies to optimize patient management. The greatest risk for pneumonia was in subjects with multiple pneumonia risk factors.

The frequency of, and adherence to, single maintenance and reliever therapy instructions in asthma: a descriptive analysis

Inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combinations are recommended regular maintenance options for asthma. ICS/LABAs containing formoterol may also be indicated for single maintenance and reliever therapy (SMART). This analysis evaluated the frequency of SMART dosing of budesonide/formoterol fixed-dose combination (BFC) in the United Kingdom. Secondary objectives were to assess adherence and use of short-acting ß2-agonists (SABAs). This was a descriptive analysis of treatment patterns using the UK Clinical Practice Research Datalink-GP OnLine Database data (2009–2013). SMART dosing was determined when prescription instructions contained guidance for daily dosing plus ‘and when required’. Treatment and prescription refill patterns of BFC and SABA were described in the year following the index date to identify adherence and SMART dosing instructions versus other dosing regimens. Of 14,818 patients identified, 173 (1.2%) had evidence of prescriptions for SMART dosing at their index BFC prescription. Despite being prescribed SMART dosing, 91 of 173 patients (53%) were additionally dispensed SABA in the year following the index date. The mean number of BFC inhalers used was less than required for daily treatment for SMART and non-SMART dosing groups (4.7 and 4.8, respectively).This analysis suggests that SMART dosing is infrequent when examining dosing instructions. Therefore, results of randomised clinical trials using SMART dosing may not translate to clinical practice in the United Kingdom because of the low level of SMART prescription, concurrent use of SABA, and inadequate refill persistence observed. Further research is needed to understand SMART dosing in real-world clinical practice.

The feasibility of using multiple databases to study rare outcomes: the potential effect of long-acting beta agonists with inhaled corticosteroid therapy on asthma mortality.

Long‐acting beta agonists (LABAs) when used without concomitant inhaled corticosteroids (ICS) increase the risk of asthma‐related deaths, but the effect on asthma‐related death of LABA used in combination with ICS therapy is unknown. To address this question, we explored the feasibility of conducting an observational study using multiple US health care data sources.