Effect of zanamivir on duration and resolution of influenza symptoms

Background: Zanamivir is a neuraminidase inhibitor, the first of a new clas s of drugs with potent, specific antiviral activity against influenza A and B. Administration by inhalation results in direct delivery to the respirat ory tract, the principal site of viral replication. Objective: This study was undertaken to determine the effectiveness of zana mivir on duration and resolution of influenza symptoms. Methods: Using a method similar to that employed in amantadine treatment st udies to obtain supporting evidence of efficacy for US Food and Drug Admini stration consideration, pooled data from 6 zanamivir phase II and III clini cal trials involving primarily previously healthy adults were analyzed to c ategorize patients as accelerated resolvers (temperature <37.8<degrees>C le ss than or equal to 24 hours after dosing, plus a greater than or equal to 50% reduction in symptom score by 36 hours), early resolvers (temperature < 37.8<degrees>C less than or equal to 36 hours after dosing), and nonacceler ated resolvers (febrile >36 hours after dosing). Patients in the accelerate d and early categories were termed rapid resolvers; the others were slow re solvers. Patients recorded their symptom severity, temperature, ability to perform normal daily activities, and use of relief medication on a diary ca rd. The primary end point of median time to alleviation of symptoms was als o reexamined, with the additional requirement that patients were not taking relief medication when their symptoms were alleviated. This analysis was i ntended to control for the possible effect of relief medication on the prim ary end point. Results: In the influenza-positive population (n = 1572), significantly mor e zanamivir-treated patients were rapid resolvers compared with those recei ving placebo (807 [72%] vs 765 [64%], P < 0.001). Significant benefits of z anamivir treatment were observed in patients with a baseline temperature of <greater than or equal to>37.8 degreesC (630 [68%] vs 595 [57%], P < 0.001 ) or <greater than or equal to> 38.3 degreesC (382 [67%] vs 365 [52%], P < 0.001) and in patients considered by their physician to have severe symptom s at the start of therapy (252 [70%] vs 222 [63%], P = 0.02). Differences w ere even more apparent in patients with high-risk conditions (74% vs 53%, P = 0.014) and in those aged <greater than or equal to>50 years (70% vs 54%, P = 0.005). Zanamivir treatment was also associated with a significant red uction in time to alleviation of symptoms with no use of relief medication. This was particularly noticeable in those aged greater than or equal to 50 years; time to alleviation was 13 days in patients receiving placebo and 6 days in patients receiving zanamivir (P < 0.001). In these trials, adverse events were reported at a similar frequency in patients receiving zanamivi r and those receiving placebo. Conclusions: Zanamivir is more effective than placebo in patients with infl uenza at providing early symptom relief and a reduced duration of illness a t a time when use of relief medication has ended. These benefits are seen a cross different patient groups but appear to be particularly marked in pati ents who are aged <greater than or equal to>50 years, who have underlying i llnesses, who are considered high risk, or who are more severely ill at the beginning of therapy.