title: A randomized controlled double-masked trial of albuterol add-on therapy in patients with multiple sclerosis.
abstract: BACKGROUND
  Interleukin 12 (IL-12), a cytokine that promotes generation of helper T cells subtype 1, is increased in multiple sclerosis. Albuterol sulfate, a β2-adrenergic agonist, reduces IL-12 expression, so we tested the effect of albuterol as an add-on treatment to glatiramer acetate therapy.
  
  
  OBJECTIVE
  To investigate the clinical and immunologic effects of albuterol treatment as an add-on therapy in patients starting glatiramer acetate treatment.
  
  
  METHODS
  Single-center double-masked clinical trial.
  
  
  METHODS
  Academic research. Patients Subjects with relapsing-remitting multiple sclerosis.
  
  
  METHODS
  In this single-center double-masked clinical trial, subjects with relapsing-remitting multiple sclerosis were randomized to receive a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of albuterol daily for 2 years. The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years, and the primary immunologic end point was the change in expression of IL-13 and interferon γ at each study time point. The classification level of evidence from this trial is C for each question, as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol.
  
  
  RESULTS
  Forty-four subjects were randomized to receive glatiramer acetate plus albuterol or glatiramer acetate plus placebo, and 39 subjects contributed to the analysis. Improvement in the Multiple Sclerosis Functional Composite was observed in the glatiramer acetate plus albuterol group at the 6-month (P = .005) and 12-month (P = .04) time points but not at the 24-month time point. A delay in the time to first relapse was also observed in the glatiramer acetate plus albuterol group (P = .03). Immunologically, IL-13 and interferon-γ production decreased in both treatment groups, and a treatment effect on IL-13 production was observed at the 12-month time point (P < .05). Adverse events were generally mild, and only 3 moderate or severe events were considered related to the treatment.
  
  
  CONCLUSIONS
  Treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00039988.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. skhoury@rics.bwh.harvard.edu
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
authors.forename: Brian C
authors.initials: BC
authors.lastname: Healy
authors.forename: Pia
authors.initials: P
authors.lastname: Kivisäkk
authors.forename: Vissia
authors.initials: V
authors.lastname: Viglietta
authors.forename: Svetlana
authors.initials: S
authors.lastname: Egorova
authors.forename: Charles R G
authors.initials: CR
authors.lastname: Guttmann
authors.forename: Josiah F
authors.initials: JF
authors.lastname: Wedgwood
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.forename: Guy
authors.initials: G
authors.lastname: Buckle
authors.forename: Sandra
authors.initials: S
authors.lastname: Cook
authors.forename: Susheel
authors.initials: S
authors.lastname: Reddy
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy*; D016017:Odds Ratio; D010455:Peptides / Q000627:therapeutic use*; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000318:Adrenergic beta-Agonists; D018793:Interleukin-13; D010455:Peptides; D000068717:Glatiramer Acetate; D007371:Interferon-gamma; D000420:Albuterol