Asthma Clinical Research Network (ACRN)
Salmeterol Off CorticoSteroids (SOCS)
In patients with moderate asthma whose symptoms are well-controlled by using an inhaled ß-agonist on an "as-needed" basis and an ICS on a scheduled basis, salmeterol on a scheduled basis has the same effects as ICS and as placebo with respect to morning peak expiratory flow and other asthma outcome measures.
The SOCS and SLIC (Salmeterol ± Inhaled Corticosteroids) trials were conducted in tandem with a common 6-week run-in period on ICS. At the end of the run-in period, the milder patients were allocated to SOCS (FEV1 > 80% predicted, PEF variability £ 20%) and the more moderate patients allocated to SLIC. The SOCS patients were randomized to salmeterol (42 µg bid), triamcinolone (400 µg bid), or placebo. Randomized treatment continued for 16 weeks, followed by a 6-week placebo run-out period. The primary outcome variable was the change in AM PEF during the double-blind treatment period. Secondary endpoints included markers of asthma severity, such as FEV1, symptom diaries, ß-agonist rescue, quality-of-life scores, methacholine responsiveness, and asthma exacerbations. Markers of inflammation were evaluated via sputum induction on all patients and bronchoalveolar lavage and bronchial biopsy on a subset of patients.
Enrollment for the SOCS and SLIC studies began in February 1997 and the last subject visits were completed in January 1999. There were 164 randomized patients (54, 54, and 56 on salmetrol, triamcinolone, and placebo, respectively). No significant differences between the salmeterol and triamcinolone groups were observed with respect to AM PEF, PM PEF, asthma symptom scores, rescue albuterol sulfate use, and quality of life. Both active treatments were superior to placebo. The salmeterol group had more treatment failures than the triamcinolone group (13/54 [24%] vs 3/54 [6%]; p = .004) and more asthma exacerbations (11/54 [20%] vs 4/54 [7%]; p = .04). Thus, patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control. The major publication appeared in JAMA:
Lazarus S, Boushey H, Fahy J, Chinchilli V, Lemanske R, Sorkness C, Kraft M, Fish J, Peters S, Craig T, Drazen J, Ford J, Israel E, Martin R, Mauger E, Nachman S, Spahn J, Szefler S, and the Asthma Clinical Research Network. Long-acting ß2 -agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: A randomized controlled trial. JAMA 2001; 285(20):2583-2593.
Asthma Clinical Research Network (ACRN)
SaLmeterol ± Inhaled Corticosteroids (SLIC)
In patients with moderate asthma whose symptoms are suboptimally controlled by using an inhaled ß-agonist on an "as-needed" basis and an ICS on a scheduled basis, the addition of salmeterol on a scheduled basis has no effect on ICS dose reduction and/or elimination over time without a concomitant increase in asthmatic symptoms, or a decrease in the protection against methacholine-induced bronchoconstriction.
The SOCS (Salmeterol Off Corticosteroids) and SLIC trials were conducted in tandem with a common 6-week run-in period on ICS. At the end of the run-in period, the milder patients were allocated to SOCS (FEV1 > 80% predicted, PEF variability £ 20%) and the more moderate patients allocated to SLIC. Patients allocated into SLIC underwent two randomizations, as indicated below in the schematic diagram. The primary outcome variable in SLIC was time to treatment failure, defined as a significant decrease in FEV1, decrease in PEF, increase in symptoms, or increase rescue albuterol use relative to baseline.
Enrollment for the SOCS and SLIC studies began in February 1997 and the last subject visits were completed in January 1999. Treatment failure occurred in 8.3% (95% CI, 2%-15%) of the SL(-)IC group 8 weeks after triamcinolone treatment was reduced compared with 2.8% (95% CI, 0%-7%) of the SL(+)IC group during the same period. Treatment failure occurred in 46.3% (95% CI, 34%-59%) of the SL(-)IC group 8 weeks after ICS was eliminated compared with 13.7% (95% CI, 5%-22%) of the SL(+)IC group. The relative risk (95% CI) at the end of the ICS elimination phase of the SL(-)IC groupt to the SL(+)IC group was 4.3 (2.0-9.2, p < .001). Thus, in patients with persistent asthma suboptimally controlled by ICS monotherapy but whose asthma symptoms improve after addition of salmeterol, a substantial reduction (50%) in ICS dose can occur without a significant loss of asthma control. However, total elimination of ICS therapy results in a significant deterioration in asthma control and cannot be recommended. The major publication appeared in JAMA:
Lemanske J, Sorkness C, Mauger E, Lazarus S, Boushey H, Fahy J, Drazen J, Chinchilli V, Craig T, Fish J, Ford J, Israel E, Kraft M, Martin R, Nachman S, Peters S, Spahn J, Szefler S, and the Asthma Clinical Research Network. Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: A randomized controlled trial. JAMA 2001; 285(20):2594-2603.