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

Abstract

PurposePrior 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 methodsThis 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.ResultsWe 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.ConclusionOur findings suggest urgent need for reappraisal of when patients need specialist care and consideration of nonsteroid therapy.

Rational oral corticosteroid use in adult severe asthma: A narrative review

“…A number of observational studies suggest a direct dose–response relationship between maintenance OCS use and complications, accompanied by a significant increase in asthma burden and healthcare costs . In a retrospective analysis of 12 697 asthma patients treated with SCS (oral or parenteral) for ≥6 months and 12 697 non‐steroid users, patients with low SCS exposure (i.e.…”

“…Recent evidence suggests that even short burst of OCS can be associated with AE, and each OCS prescription results in a cumulative burden, regardless of the dose and duration . Longitudinal, retrospective data indicate AE increase in a dose‐dependent manner above cumulative exposures of 1.0–2.5 g prednisone equivalent, and for some outcomes at cumulative exposures of <1 g …”

“…Unfortunately, maintenance OCS use is a leading cause of serious drug‐related adverse effects (AE), and substantially increasing healthcare costs . Emerging evidence suggests that repetitive bursts of OCS for acute asthma exacerbations also lead to cumulative AE . This is disturbing considering that a high proportion of severe asthma patients require ≥2 OCS bursts per year for managing exacerbations …”

ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions

“…Whether 3 or 5 days of OCS is more accurate for discriminating a mild from a severe exacerbation will probably not be addressable in terms of evidence. 1) Herein we report an expert-based opinion that definitely does not intend to change the definition used in trials in order to keep them comparable; and 2) as the harmfulness of cumulative doses of corticosteroids is obvious above 0.5 g per year [14], a 5-day-based definition would make better fit this OCS-associated risk with the threshold of two exacerbations. Although variable among countries and systems, emergency visit or hospitalisation, the task force members base hospitalisation or initiation of treatment with OCS on the Global Initiative for Asthma (GINA) or British Thoracic Society recommendations to improve standardisation.…”

Matching‐adjusted comparison of oral corticosteroid reduction in asthma: Systematic review of biologics

“…1,2 This burden is even greater for patients receiving maintenance treatment with oral corticosteroids (OCS) who may experience increased risk of chronic comorbidities including type 2 diabetes mellitus, osteoporosis, and cataracts; neuropsychiatric effects including insomnia and depression; and infections and cardiovascular, metabolic, and gastrointestinal complications. [3][4][5] For patients who initiated short-term or maintenance treatment with systemic corticosteroids (SCS) followed over a median of more than 7 years, increasing cumulative SCS exposure resulted in greater risk of potentially life-changing adverse outcomes, even for some patients with cumulative exposure of only 0.5-<1 g. 3 Reduction of OCS exposure is therefore an important treatment goal for patients with severe OCS-dependent asthma.…”