Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma

Abstract

This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.

Impact of Race on Asthma Treatment Failures in the Asthma Clinical Research Network

“…However, data from the SMART study (a large multicenter trial examining safety of salmeterol) (3) and the current findings suggest that differential response to LABAs in African Americans exist. Indeed, despite the fact that multiple studies of similar and smaller size in predominantly white populations had demonstrated superiority of added salmeterol in exacerbations, symptom control, and medication use (19)(20)(21), the only prospective asthma study in African Americans to date (salmeterol or ICS vs. ICS alone in 475 African Americans) (22) revealed a blunted response to LABA in African Americans. That study failed to demonstrate that exacerbations were decreased or that asthma control (except night-time awakenings) was improved by the addition of salmeterol.…”

Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option?

“…4) [18]. This provides additional evidence that a treatment regimen involving an increase of the maintenance ICS dose alone has limited additional benefit in improving symptom control in most patients [7,15,[31][32][33][34]. Such a regimen may result in overtreatment with ICS, potentially increasing the risk of long-term side-effects [33,35].…”

“…Clinically relevant exacerbations and as-needed medication use were the key effectiveness measures, as often used in clinical practice. In addition, patients were not excluded from the study based on reversibility criteria as in standard efficacy trials of LABA therapy [7,13,15], a factor potentially reducing the applicability of clinical trial findings to routine clinical practice [16].…”

“…In addition to being more convenient than separate inhalers, combination inhalers control asthma at lower doses of ICS compared with ICS alone [6,7] and may prevent patients from over-relying on their LABA or short-acting b 2 -agonist (SABA) at the expense of ICS therapy. Currently, there are two ICS/LABA combination inhalers available: budesonide/formoterol and salmeterol/fluticasone.…”

Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma

“…Systematic reviews have found a 12-14% reduction in the risk of an exacerbation with traditional ICS/LABA maintenance therapy plus SABA for relief compared with a higher ICS dose plus SABA in patients with moderate to severe asthma (17,18). However, the value of increasing ICS dose for improving daily asthma control may be limited (19).…”