Inhaled, nasal and topical corticosteroid burden and association with corticosteroid-associated adverse events.
Patients with type 2 inflammation-associated diseases are often treated with multiple formulations of corticosteroids. Long-term risks of using combinations of local corticosteroids are poorly characterised.
Using Danish nationwide databases, investigate associations between local corticosteroid exposure and 11 corticosteroid exposure-associated conditions compared to non-users, and eventual dose-response relationship for exposed individuals.
Systemic corticosteroid-naïve adults who redeemed inhaled, nasal and/or topical corticosteroids 2000-2012 were matched with non-initiators and followed for up to 23 years. Overall (inhaled, nasal and topical) exposure was calculated for 6-month periods as low (<1.25 daily prednisolone-equivalent mg), moderate (1.25-2.5 mg) or high (>2.5 mg). Competing risk Cox models with time-varying effects were used, presented as HR per additional 6-month period of exposure.
Overall, 292,393 local corticosteroid users were included (mean age 45, 47.7% female). Corticosteroid exposure-associated condition incidences were generally low, but all conditions had higher subdistribution-HRs in users, ranging from 1.4 to 3.8 for cataracts and obesity (p<0.001).For local corticosteroid users, increased risk per 6-month exposure was observed for osteoporosis (low-high dose: HRs 1.01-1.10), obesity (1.03-1.03) and pneumonia (1.03-1.15). Risk of cardiovascular disease, heart failure, cataract and gastroesophageal reflux disease increased with high-dose exposure only at HRs 1.03, 1.02, 1.04 and 1.04 per additional 6-month period of exposure, respectively.Stratified by formulation, high-dose inhaled and topical corticosteroids demonstrated the strongest associations.
In individuals using local corticosteroids, the overall corticosteroid burden, including shorter periods of high-dose exposure, associates with corticosteroid exposure-associated adverse events albeit with generally low incidence and hazard.
Using Danish nationwide databases, investigate associations between local corticosteroid exposure and 11 corticosteroid exposure-associated conditions compared to non-users, and eventual dose-response relationship for exposed individuals.
Systemic corticosteroid-naïve adults who redeemed inhaled, nasal and/or topical corticosteroids 2000-2012 were matched with non-initiators and followed for up to 23 years. Overall (inhaled, nasal and topical) exposure was calculated for 6-month periods as low (<1.25 daily prednisolone-equivalent mg), moderate (1.25-2.5 mg) or high (>2.5 mg). Competing risk Cox models with time-varying effects were used, presented as HR per additional 6-month period of exposure.
Overall, 292,393 local corticosteroid users were included (mean age 45, 47.7% female). Corticosteroid exposure-associated condition incidences were generally low, but all conditions had higher subdistribution-HRs in users, ranging from 1.4 to 3.8 for cataracts and obesity (p<0.001).For local corticosteroid users, increased risk per 6-month exposure was observed for osteoporosis (low-high dose: HRs 1.01-1.10), obesity (1.03-1.03) and pneumonia (1.03-1.15). Risk of cardiovascular disease, heart failure, cataract and gastroesophageal reflux disease increased with high-dose exposure only at HRs 1.03, 1.02, 1.04 and 1.04 per additional 6-month period of exposure, respectively.Stratified by formulation, high-dose inhaled and topical corticosteroids demonstrated the strongest associations.
In individuals using local corticosteroids, the overall corticosteroid burden, including shorter periods of high-dose exposure, associates with corticosteroid exposure-associated adverse events albeit with generally low incidence and hazard.
Authors
Julius Håkansson Julius Håkansson, Skov Skov, Wuyts Andersen Wuyts Andersen, Ali Ali, Thomsen Thomsen, Løkke Løkke, Ibsen Ibsen, Hilberg Hilberg, Meteran Meteran, Johnsen Johnsen, Schwarz Schwarz, Backer Backer, Ulrik Ulrik
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