Assessment of montelukast, doxofylline, and tiotropium with budesonide for the treatment of asthma: which is the best among the second-line treatment? A randomized trial.

Data comparing various second-line treatments for asthma with subjective and objective assessment are lacking. This study aimed to compare the efficacy and safety of montelukast, doxofylline, and tiotropium with a low-dose budesonide in patients with mild to moderate persistent asthma. Patients, all of whom were concurrently using inhaled budesonide (400 µg), were treated for 6 months with formoterol (12 µg), montelukast (10 mg), doxofylline (400 mg), or tiotropium (18 µg). Outcomes included forced expiratory volume in 1 second (FEV1), Saint George Respiratory Questionnaire (SGRQ) scores, asthma symptom scores (daytime and nighttime), and assessment of tolerability and rescue medication use. A total of 297 patients completed the study. In all 4 groups, significant improvements were observed in all the outcome measures, with formoterol treatment having greater and earlier improvements than the other 3 second-line controller medications with budesonide. Among the second-line treatments, monteradlukast improved the FEV1 from day 45 (P < 0.01), SGRQ scores from day 30 (P < 0.0001), daytime scores from day 30 (P < 0.05), nighttime scores from day 30 (P < 0.0001), and rescue medication use from day 15 (P < .0001) at a faster rate than doxofylline or tiotropium with budesonide. No patients discontinued the treatment because of adverse reactions. Among the tested second-line treatment regimens, the budesonide/montelukast combination was found to be superior to either the budesonide/doxofylline or budesonide/tiotropium combination in all the outcome measures without adversely affecting the tolerability of the patients. Further clinical studies with blinding techniques are likely to be useful.