Adverse Outcomes from Initiation of Systemic Corticosteroids for Asthma: Long-term Observational Study

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.