The rationale for removing a boxed safety warning about long-acting beta-agonist (LABA) bronchodilators from inhalants combining LABA with a corticosteroid was described in recent commentary by the FDA, in accompanying independent analysis of research from a collaboration of inhalant manufacturers.

The warning was issued in 2003 in response to asthma-related hospitalizations, intubations and deaths linked to LABA use. As the incidents were likely to have occurred without concurrent inhaled corticosteroid, the FDA mandated in 2011 that the 4 manufacturers marketing inhaled LABA plus corticosteroid combination products for asthma in the US conduct prospective, randomized, controlled trials comparing the safety of their product with that of inhaled glucocorticoid alone.

With concurrence of the FDA, the manufacturers harmonized their trial methods and established an independent joint oversight committee to provide a final combined analysis of 4 trials conducted in adolescents and adults.