Anticholinergic vs Long-Acting β-Agonist in Combination With Inhaled Corticosteroids in Black Adults With Asthma: The BELT Randomized Clinical Trial.
OBJECTIVE
The efficacy and safety of long-acting β-agonists (LABAs) have been questioned. Black populations may be disproportionately affected by LABA risks.


OBJECTIVE
To compare the effectiveness and safety of tiotropium vs LABAs, when used with inhaled corticosteroids (ICS) in black adults with asthma and to determine whether allelic variation at the Arg16Gly locus of the β2-adrenergic receptor (ADRB2) geneis associated with treatment response.


METHODS
A multisite (n = 20), open-label, parallel-group, pragmatic randomized clinical trial conducted from March 2011 through July 2013, enrolling black adults with moderate to severe asthma in the United States.


METHODS
Patients eligible for, or receiving, step 3 or step 4 combination therapy per National Heart, Lung, and Blood Institute guidelines, received ICS plus either once-daily tiotropium (n = 532) or twice-daily LABAs (n = 538,) and were followed up for up to 18 months. Patients underwent genotyping, attended study visits at baseline, 1, 6, 12, and 18 months, and completed monthly questionnaires.


METHODS
The primary outcome was time to asthma exacerbation, defined as a worsening asthma event requiring oral or parenteral corticosteroids. Secondary outcomes included patient-reported outcomes (Asthma Quality of Life Questionnaire, Asthma Control Questionnaire [ACQ], Asthma Symptom Utility Index, and Asthma Symptom-Free Days questionnaire), spirometry (FEV1), rescue medication use, asthma deteriorations, and adverse events.


RESULTS
There was no difference between LABA + ICS vs tiotropium + ICS in time to first exacerbation (mean No. of exacerbations/person-year, 0.42 vs 0.37 (rate ratio, 0.90 [95% CI, 0.73 to 1.11], log-rank P = .31). There was no difference in change in FEV1 at 12 months (0.003 L for LABA + ICS vs -0.018 L for tiotropium + ICS; between-group difference, 0.020 [95% CI, -0.021 to 0.061], P = .33) and at 18 months (-0.053 L vs -0.078 L; between-group difference, 0.025 [95% CI, -0.045 to 0.095], P = .49). There were no differences in ACQ score at 18 months (change in score from baseline, -0.68 for LABA + ICS vs -0.72 for tiotropium + ICS; between-group difference, 0.04 [95% CI, -0.18 to 0.27], P = .70). There were no differences in other patient-reported outcomes. Arg16Gly ADRB2 alleles were not associated with differences in the effects of tiotropium + ICS vs LABA + ICS (hazard ratio for time to first exacerbation, 0.84 [95% CI, 0.47 to 1.51] for Arg/Arg vs 0.85 [95% CI, 0.63 to 1.15] for Arg/Gly or Gly/Gly, P = .97).


CONCLUSIONS
Among black adults with asthma treated with ICS, adding a LABA did not improve time to asthma exacerbation compared with adding tiotropium. These findings were not affected by polymorphisms at the Arg16Gly locus of ADRB2. These findings do not support the superiority of LABA + ICS compared with tiotropium + ICS for black patients with asthma.


BACKGROUND
ClinicalTrials.gov identifier: NCT01290874.
Brigham and Women's Hospital, Boston, Massachusetts2now with National Jewish Health, Denver, Colorado.
Michael E
ME
Wechsler
Olmsted Medical Center, Rochester, Minnesota.
Barbara P
BP
Yawn
Brigham and Women's Hospital, Boston, Massachusetts.
Anne L
AL
Fuhlbrigge
University of Colorado, Denver, Colorado.
Wilson D
WD
Pace
Harvard Clinical Research Institute, Boston, Massachusetts6now with Duke Clinical Research Institute, Durham, North Carolina.
Michael J
MJ
Pencina
Harvard Clinical Research Institute, Boston, Massachusetts7Boston University, Boston, Massachusetts.
Gheorghe
G
Doros
Brigham and Women's Hospital, Boston, Massachusetts8now with Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
Shamsah
S
Kazani
Brigham and Women's Hospital, Boston, Massachusetts.
Benjamin A
BA
Raby
Harvard Clinical Research Institute, Boston, Massachusetts.
Jane
J
Lanzillotti
Olmsted Medical Center, Rochester, Minnesota.
Suzanne
S
Madison
Brigham and Women's Hospital, Boston, Massachusetts.
Elliot
E
Israel
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use*; D001741:Black or African American; D000420:Albuterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000627:therapeutic use; D005260:Female; D005540:Forced Expiratory Flow Rates; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D000069447:Tiotropium Bromide
C553443:ADRB2 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; D018680:Cholinergic Antagonists; D004983:Ethanolamines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D018343:Receptors, Adrenergic, beta-2; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide