Long-term safety and efficacy of zafirlukast in the treatment of asthma: interim results of an open-label extension trial.
BACKGROUND
Current guidelines recommend anti-leukotriene agents as alternative treatments for mild persistent asthma; however, information on their long-term safety and efficacy is needed.


OBJECTIVE
To evaluate long-term safety and efficacy of and compliance with oral zafirlukast (Z; 20 mg BID) during the first 39 weeks of ongoing, multicenter, open-label extension (OLE) of a previously reported 13-week, randomized (2:1), double-blind (DB), placebo (P)-controlled trial in mild-to-moderate asthmatic patients treated previously with beta2-agonists alone.


METHODS
Patients (12 to 76 years; FEV1 > or = 55% predicted) elected to enter OLE after completing the DB trial. Safety evaluated by adverse events (AEs), laboratory tests, and physical and electrocardiographic examinations. Efficacy assessed by spirometry measurements [FEV1, FEV1 % predicted, personal-best (post-bronchodilator) FEV1] and treatment failure rates. Compliance was calculated as percentage of treatment dispensed. After a visit at OLE week 3 (week 16), patients had visits every 12 weeks.


RESULTS
A total of 443 patients (nz-->z = 310, np-->z = 133) entered the OLE. Results through the OLE period showed that 80% of patients overall reported AEs. Of patients randomized to Z and P during DB period, 68% and 67%, respectively, reported AEs during quarter I (Q1); percentage of Z-treated patients reporting AEs during the OLE ranged from 66% (Q2) to 44% (Q4). Review by quarters showed occurrence of AEs in Z-treated groups (Q2-4) was similar to that in P group (Q1). Compared with baseline (week 0), modest yet significant improvements (P < or = .02) in all spirometry measurements were noted in Z --> Z and P --> Z groups at OLE week 3, with sustained effects noted during OLE period. Treatment failure rates during OLE ranged from 7.2% (Q2) to 3.3% (Q4). Mean compliance ranged from 98% (OLE week 3) to 95% (OLE week 39).


CONCLUSIONS
Long-term treatment with zafirlukast was safe and well tolerated in asthmatic patients. Sustained efficacy and asthma control and good compliance were observed over extended treatment period. Results demonstrate long-term safety and effectiveness of and compliance with this anti-leukotriene agent.
Grossman
J
J
VIVRA Research, Tucson, Arizona 85705, USA.
Smith
L J
LJ
Wilson
A M
AM
Thyrum
P T
PT
D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D005260:Female; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome
D018927:Anti-Asthmatic Agents; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; C062735:zafirlukast