title: Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone.
abstract: BACKGROUND
  Concerns remain about the safety of adding long-acting β2-agonists to inhaled glucocorticoids for the treatment of asthma. In a postmarketing safety study mandated by the Food and Drug Administration, we evaluated whether the addition of formoterol to budesonide maintenance therapy increased the risk of serious asthma-related events in patients with asthma.
  
  
  METHODS
  In this multicenter, double-blind, 26-week study, we randomly assigned patients, 12 years of age or older, who had persistent asthma, were receiving daily asthma medication, and had had one to four asthma exacerbations in the previous year to receive budesonide-formoterol or budesonide alone. Patients with a history of life-threatening asthma were excluded. The primary end point was the first serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization), as assessed in a time-to-event analysis. The noninferiority of budesonide-formoterol to budesonide was defined as an upper limit of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The primary efficacy end point was the first asthma exacerbation, as assessed in a time-to-event analysis.
  
  
  RESULTS
  A total of 11,693 patients underwent randomization, of whom 5846 were assigned to receive budesonide-formoterol and 5847 to receive budesonide. A serious asthma-related event occurred in 43 patients who were receiving budesonide-formoterol and in 40 patients who were receiving budesonide (hazard ratio, 1.07; 95% confidence interval [CI], 0.70 to 1.65]); budesonide-formoterol was shown to be noninferior to budesonide alone. There were two asthma-related deaths, both in the budesonide-formoterol group; one of these patients had undergone an asthma-related intubation. The risk of an asthma exacerbation was 16.5% lower with budesonide-formoterol than with budesonide (hazard ratio, 0.84; 95% CI, 0.74 to 0.94; P=0.002).
  
  
  CONCLUSIONS
  Among adolescents and adults with predominantly moderate-to-severe asthma, treatment with budesonide-formoterol was associated with a lower risk of asthma exacerbations than budesonide and a similar risk of serious asthma-related events. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01444430 .).
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Stephen P
authors: SP
authors: Peters
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Eugene R
authors: ER
authors: Bleecker
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Giorgio W
authors: GW
authors: Canonica
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Yong B
authors: YB
authors: Park
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Ricardo
authors: R
authors: Ramirez
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Sally
authors: S
authors: Hollis
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Harald
authors: H
authors: Fjallbrant
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Carin
authors: C
authors: Jorup
authors: From Wake Forest School of Medicine, Winston-Salem, NC (S.P.P., E.R.B.); University of Genoa, Genoa, Italy (G.W.C.); Hallym University, Seoul, South Korea (Y.B.P.); Centro de Investigacion y Atencion Integral, Durango, Mexico (R.R.); AstraZeneca, Macclesfield, United Kingdom (S.H.); AstraZeneca Research and Development, Gothenburg, Sweden (H.F., C.J.); and AstraZeneca, Gaithersburg, MD (U.J.M.).
authors: Ubaldo J
authors: UJ
authors: Martin
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000517:prevention & control; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068759:Formoterol Fumarate / Q000008:administration & dosage* / Q000009:adverse effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D019819:Budesonide; D000068759:Formoterol Fumarate