Evaluation of the effects of zafirlukast 40 mg b.i.d. in addition to preexisting therapy of high-dose inhaled steroids on symptomatic patients with reversible respiratory obstruction : preliminary data

Clinical evidence of the efficacy of zafirlukast is available for mild-to-moderate asthma, but further evidence is needed on its use in the more severe forms, uncontrolled by traditional therapy. The aim of this study was to evaluate the efficacy of zafirlukast 40 mg b.i.d. as an add-on to high dose inhaled corticosteroids (HDICs). A secondary aim was to assess the drug's safety and the patients' evaluation of oral therapy and compliance. Twenty-two asthmatic patients (13 females, aged 12-70 years) taking short-acting beta 2-agonists as needed and HDICs as maintenance therapy, entered a 2-week screening phase. At the end, 18 patients with baseline forced expiratory volume (FEV)1 = 50-80% of predicted, a reversibility of > or = 15% and a > or = 10 weekly total of daytime symptom score, were given zafirlukast 40 mg b.i.d. and were reevaluated every 4 weeks for 12 weeks. Adverse events, withdrawals and changes in hematology were recorded. A diary and a questionnaire were used for subjective patient assessment. Sixteen patients (nine females, mean age 40) completed the study. Mean FEV1, (absolute value and percentage vs. predicted) was significantly higher (p < 0.05) vs. baseline after zafirlukast, with a mean improvement of 0.2 l/sec (2.4 vs. 2.2) or 6% (76% vs. 70%) of predicted. Similarly, a significant (p < 0.001) increase in peak expiratory flow was observed (6 vs. 5.5 l/sec). There was no statistically significant variation in forced expiratory flow 25-75. Analysis of the diaries showed a statistically significant reduction (p < 0.05) of morning symptoms (0.73 vs. 4.6) and of daytime symptoms score (2.3 vs. 5.3). There was no evidence of improvement in night time symptoms and use of beta 2-agonists. Three patients experienced adverse events and four suffered a single exacerbation not requiring hospital admission. Subjective evaluation was positive: 75% reported an improvement, 25% found no change and 40% particularly appreciated the oral therapy. In conclusion, treatment with zafirlukast (40 mg b.i.d.) showed a significant improvement in function parameters and symptoms. Zafirlukast was well tolerated and accepted by patients. Further research is needed, as the small number of patients does not allow definitive conclusions to be drawn.