TY - JOUR
T1 - Adjunctive Systemic Corticosteroids for Pulmonary Exacerbations of Cystic Fibrosis
AU - STOP2 Investigators
AU - McElvaney, Oliver J.
AU - Heltshe, Sonya L.
AU - Odem-Davis, Katherine
AU - West, Natalie E.
AU - Sanders, Don B.
AU - Fogarty, Barbra
AU - VanDevanter, Donald R.
AU - Flume, Patrick A.
AU - Goss, Christopher H.
N1 - Publisher Copyright:
Copyright © 2024 by the American Thoracic Society.
PY - 2024/5/1
Y1 - 2024/5/1
N2 - Rationale: Pulmonary exacerbations (PEx) remain the most common cause of morbidity, recurrent hospitalization, and diminished survival in people with cystic fibrosis (PWCF) and are characterized by excess inflammation. Corticosteroids are potent, widely available antiinflammatory drugs. However, corticosteroid efficacy data from randomized controlled trials in PWCF are limited. Objectives: To determine whether adjunctive systemic corticosteroid therapy is associated with improved outcomes in acute CF PEx. Methods: We performed a secondary analysis of Standardized Treatment of Pulmonary Exacerbations 2 (STOP2), a large multicenter randomized controlled trial of antimicrobial treatment durations for adult PWCF presenting with PEx, that included the use of corticosteroids as a stratification criterion in its randomization protocol. Corticosteroid treatment effects were determined after propensity score matching for covariates including age, sex, baseline forced expiratory volume in 1 second (FEV1), genotype, and randomization arm. The primary outcome measure was the change in percentage predicted FEV1 (ppFEV1). Symptoms, time to next PEx, and the incidence of adverse events (AEs) and serious adverse events (SAEs) were assessed as secondary endpoints. Phenotypic factors associated with the clinical decision to prescribe steroids were also investigated. Results: Corticosteroids were prescribed for 168 of 982 PEx events in STOP2 (17%). Steroid prescription was associated with decreased baseline ppFEV1, increased age, and female sex. Cotreatment with corticosteroids was independent of treatment arm allocation and did not result in greater mean ppFEV1 response, longer median time to next PEx, or more substantial symptomatic improvement compared with propensity-matched PWCF receiving antibiotics alone. AEs were not increased in corticosteroid-treated PWCF. The total number of SAEs—but not the number of corticosteroid-related or PEx-related SAEs—was higher among patients receiving corticosteroids. Conclusions: Empiric, physician-directed treatment with systemic corticosteroids, although common, is not associated with improved clinical outcomes in PWCF receiving antibiotics for PEx.
AB - Rationale: Pulmonary exacerbations (PEx) remain the most common cause of morbidity, recurrent hospitalization, and diminished survival in people with cystic fibrosis (PWCF) and are characterized by excess inflammation. Corticosteroids are potent, widely available antiinflammatory drugs. However, corticosteroid efficacy data from randomized controlled trials in PWCF are limited. Objectives: To determine whether adjunctive systemic corticosteroid therapy is associated with improved outcomes in acute CF PEx. Methods: We performed a secondary analysis of Standardized Treatment of Pulmonary Exacerbations 2 (STOP2), a large multicenter randomized controlled trial of antimicrobial treatment durations for adult PWCF presenting with PEx, that included the use of corticosteroids as a stratification criterion in its randomization protocol. Corticosteroid treatment effects were determined after propensity score matching for covariates including age, sex, baseline forced expiratory volume in 1 second (FEV1), genotype, and randomization arm. The primary outcome measure was the change in percentage predicted FEV1 (ppFEV1). Symptoms, time to next PEx, and the incidence of adverse events (AEs) and serious adverse events (SAEs) were assessed as secondary endpoints. Phenotypic factors associated with the clinical decision to prescribe steroids were also investigated. Results: Corticosteroids were prescribed for 168 of 982 PEx events in STOP2 (17%). Steroid prescription was associated with decreased baseline ppFEV1, increased age, and female sex. Cotreatment with corticosteroids was independent of treatment arm allocation and did not result in greater mean ppFEV1 response, longer median time to next PEx, or more substantial symptomatic improvement compared with propensity-matched PWCF receiving antibiotics alone. AEs were not increased in corticosteroid-treated PWCF. The total number of SAEs—but not the number of corticosteroid-related or PEx-related SAEs—was higher among patients receiving corticosteroids. Conclusions: Empiric, physician-directed treatment with systemic corticosteroids, although common, is not associated with improved clinical outcomes in PWCF receiving antibiotics for PEx.
KW - CF
KW - PEx
KW - clinical trial
KW - corticosteroids
KW - respiratory infection
UR - http://www.scopus.com/inward/record.url?scp=85186942838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85186942838&partnerID=8YFLogxK
U2 - 10.1513/AnnalsATS.202308-673OC
DO - 10.1513/AnnalsATS.202308-673OC
M3 - Article
C2 - 38096105
AN - SCOPUS:85186942838
SN - 2329-6933
VL - 21
SP - 716
EP - 726
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
IS - 5
ER -