Repeated dosing effects of mediator antagonists in inhaled corticosteroid-treated atopic asthmatic patients.

Background: The anti-inflammatory effects of repeated dosing with mediator antagonists as add-on therapy to that with inhaled corticosteroids (ICSs) in patients with asthma remain to be fully established.

Objective: We elected to evaluate the effects of repeated dosing with fexofenadine (FEX) and montelukast (ML) at clinically recommended doses in ICS-treated asthmatic patients using adenosine monophosphate (AMP) bronchial challenge as the primary outcome.

Methods: Eighteen atopic asthmatic patients receiving a mean (+/- SEM) dose of 631 +/- 104 micro g daily of ICSs, which remained unchanged throughout the entire study, were randomized in double-blind, cross-over fashion to receive FEX, 180 mg, ML, 10 mg, or placebo (PL) for 1 week. There was a 1-week washout period prior to each randomized treatment. Measurements of the provocative concentration of a substance (ie, AMP) causing a 20% fall in FEV(1) (PC(20)) were made after each washout period and randomized treatment period.

Results: The values for AMP PC(20) after the washout period prior to each randomized treatment were not significantly different (FEX, 74 +/- 15 mg/mL; ML, 73 +/- 18 mg/mL; PL, 71 +/- 19 mg/mL). There were significant improvements (p < 0.05) in AMP PC(20) with the use of FEX (127 +/- 38 mg/mL) and ML (121 +/- 27 mg/mL) compared to PL (78 +/- 23 mg/mL). Spontaneous recovery after AMP challenge, as determined by area under the 60-min time-response curve, was significantly enhanced (p < 0.05) with the use of ML (352 +/- 95%.min [corrected]) compared to FEX (758 +/- 140%.min) and PL (683 +/- 134%.min [corrected]). Both FEX and ML significantly suppressed (p < 0.05) the levels of exhaled nitric oxide, while only ML significantly reduced (p < 0.05) the peripheral blood eosinophil count compared to PL. Morning and evening peak expiratory flow were significantly higher (p < 0.05), and the frequency of salbutamol rescue was significantly reduced (p < 0.05) with FEX and ML compared to PL.

Conclusion: Repeated dosing with FEX and ML as add-on therapy improved AMP PC(20) and other surrogate inflammatory markers along with asthma diary outcomes in ICS-treated atopic asthmatic patients. Further studies are indicated to evaluate the long-term add-on effects of FEX on asthma exacerbations.