Long-acting beta2 agonists are known to improve peak expiratory flow and reduce the symptoms of asthma. Treatment guidelines recommend that a long-acting beta2 agonist be added in patients whose asthma is not controlled by low or moderate dosages of an inhaled corticosteroid. This practice is more effective than increasing the dosage of inhaled corticosteroid. Lazarus and colleagues conducted a study to determine whether salmeterol, a long-acting beta2 agonist, could replace low-dose triamcinolone in patients whose asthma is well controlled—that is, can salmeterol be used as monotherapy?
During a six-week triamcinolone run-in period, all patients received four puffs of triamcinolone twice daily. Patients whose asthma was successfully controlled on this medication were enrolled in the Salmeterol or Corticosteroids Study (SOCS). Patients were then randomized to receive, by metered-dose inhaler, four puffs twice daily of triamcinolone, two puffs twice daily of salmeterol, or two puffs twice daily of placebo. The regimens were maintained for 16 weeks. Each patient was then entered in a six-week-long placebo run-out period.
During the course of the SOCS, patients rated their shortness of breath, chest tightness, wheezing, cough, and mucus on a three-point scale (zero = none, 3 = severe). They also recorded their use of rescue medication (albuterol), other illnesses, and hospitalizations. Evaluations every two to four weeks included an interval history, a physical examination, spirometry, and measurements of exhaled nitric oxide. An asthma-specific quality-of-life questionnaire was completed at baseline, six weeks, 22 weeks, and again at weeks 24 and 28 (run-out period). The primary outcome measured was change in morning peak expiratory flow. Patients who failed treatment were given a short course of prednisone or two puffs twice daily of open-label triamcinolone.
Of the 422 patients initially enrolled in the SOCS, 361 patients completed the triamcinolone run-in period. Of these, 56 were assigned to receive placebo, 54 to receive salmeterol, and 54 to receive triamcinolone. The three groups had no significant differences in peak expiratory flow. The failure rate in the patients treated with triamcinolone (6 percent) was lower than the failure rates in those given placebo (36 percent) or salmeterol (24 percent). Exacerbations occurred in 7 percent of patients in the triamcinolone group, 20 percent of those in the salmeterol group, and 29 percent of those in the placebo group.
Discontinuing triamcinolone (and starting placebo) was associated with a significant decrease in morning peak expiratory flow and forced expiratory volume in one second, as well as increases in the need for rescue medication and increased symptom scores. Similarly, those who switched from salmeterol to placebo had increased need for albuterol rescue and increased symptom scores.
The authors concluded that switching patients whose asthma was well controlled by an inhaled corticosteroid to salmeterol would cause a clinically significant loss of that control. Compared with patients who were given placebo, the salmeterol-treated patients had fewer symptoms and less need for rescue medication, but they had similar rates of asthma exacerbations and treatment failures.