Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study

David B Price,1,2 Frank Trudo,3 Jaco Voorham,1 Xiao Xu,4 Marjan Kerkhof,1 Joanna Ling Zhi Jie,1 Trung N Tran5 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Medical Affairs, AstraZeneca, Wilmington, DE, USA; 4Global Payer Evidence and Pricing, AstraZeneca, Gaithersburg, MD, USA; 5Medical Evidence and Observational Research, AstraZeneca, Gaithersburg, MD, USA Purpose: Prior work suggests a threshold of four courses/year of systemic corticosteroid (SCS) therapy is associated with adverse consequences. The objective of this study was to investigate the onset of adverse outcomes beginning at SCS initiation in a broad asthma population. Patients and methods: This historical matched cohort study utilized anonymized, longitudinal medical record data (1984–2017) of patients (≥18 years) with active asthma. Matched patients with first SCS prescription (SCS arm) and no SCS exposure (non-SCS arm) were followed until first outcome event. Associations between time-varying exposure measures and onset of 17 SCS-associated adverse outcomes were estimated using Cox proportional hazard regression, adjusting for confounders, in separate models. Results: We matched 24,117 pairs of patients with median record availability before SCS initiation of 9.9 and 8.7 years and median follow-up 7.4 and 6.4 years in SCS and non-SCS arms, respectively. Compared with patients in the non-SCS arm, patients prescribed SCS had significantly increased risk of osteoporosis/osteoporotic fracture (adjusted hazard ratio 3.11; 95% CI 1.87–5.19), pneumonia (2.68; 2.30–3.11), cardio-/cerebrovascular diseases (1.53; 1.36–1.72), cataract (1.50; 1.31–1.73), sleep apnea (1.40; 1.04–1.86), renal impairment (1.36; 1.26–1.47), depression/anxiety (1.31; 1.21–1.41), type 2 diabetes (1.26; 1.15–1.37), and weight gain (1.14; 1.10–1.18). A dose-response relationship for cumulative SCS exposure with most adverse outcomes began at cumulative exposures of 1.0–<2.5 g and for some outcomes at cumulative exposures of only 0.5–<1 g (vs >0–<0.5 g reference), equivalent to four lifetime SCS courses. Conclusion: Our findings suggest urgent need for reappraisal of when patients need specialist care and consideration of nonsteroid therapy. Keywords: adverse outcomes, asthma, cumulative exposure, oral corticosteroids, systemic corticosteroid

Validation of an administrative claims-based diagnostic code for pneumonia in a US-based commercially insured COPD population

David M Kern,1 Jill Davis,2 Setareh A Williams,3 Ozgur Tunceli,1 Bingcao Wu,1 Sally Hollis,4 Charlie Strange,5 Frank Trudo2 1HealthCore, Inc., Wilmington, DE, 2AstraZeneca Pharmaceuticals, Wilmington, DE, 3AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA; 4AstraZeneca Pharmaceuticals, Cheshire, UK; 5Department of Medicine, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA Objective: To estimate the accuracy of claims-based pneumonia diagnoses in COPD patients using clinical information in medical records as the reference standard.Methods: Selecting from a repository containing members’ data from 14 regional United States health plans, this validation study identified pneumonia diagnoses within a group of patients initiating treatment for COPD between March 1, 2009 and March 31, 2012. Patients with ≥1 claim for pneumonia (International Classification of Diseases Version 9-CM code 480.xx–486.xx) were identified during the 12 months following treatment initiation. A subset of 800 patients was randomly selected to abstract medical record data (paper based and electronic) for a target sample of 400 patients, to estimate validity within 5% margin of error. Positive predictive value (PPV) was calculated for the claims diagnosis of pneumonia relative to the reference standard, defined as a documented diagnosis in the medical record.Results: A total of 388 records were reviewed; 311 included a documented pneumonia diagnosis, indicating 80.2% (95% confidence interval [CI]: 75.8% to 84.0%) of claims-identified pneumonia diagnoses were validated by the medical charts. Claims-based diagnoses in inpatient or emergency departments (n=185) had greater PPV versus outpatient settings (n=203), 87.6% (95% CI: 81.9%–92.0%) versus 73.4% (95% CI: 66.8%–79.3%), respectively. Claims-diagnoses verified with paper-based charts had similar PPV as the overall study sample, 80.2% (95% CI: 71.1%–87.5%), and higher PPV than those linked to electronic medical records, 73.3% (95% CI: 65.5%–80.2%). Combined paper-based and electronic records had a higher PPV, 87.6% (95% CI: 80.9%–92.6%).Conclusion: Administrative claims data indicating a diagnosis of pneumonia in COPD patients are supported by medical records. The accuracy of a medical record diagnosis of pneumonia remains unknown. With increased use of claims data in medical research, COPD researchers can study pneumonia with confidence that claims data are a valid tool when studying the safety of COPD therapies that could potentially lead to increased pneumonia susceptibility or severity. Keywords: positive predictive value, pneumonia, validation, claims data, medical record revie