Effect of zanamivir on duration and resolution of influenza symptoms.
BACKGROUND
Zanamivir is a neuraminidase inhibitor, the first of a new class of drugs with potent, specific antiviral activity against influenza A and B. Administration by inhalation results in direct delivery to the respiratory tract, the principal site of viral replication.


OBJECTIVE
This study was undertaken to determine the effectiveness of zanamivir on duration and resolution of influenza symptoms.


METHODS
Using a method similar to that employed in amantadine treatment studies to obtain supporting evidence of efficacy for US Food and Drug Administration consideration, pooled data from 6 zanamivir phase II and III clinical trials involving primarily previously healthy adults were analyzed to categorize patients as accelerated resolvers (temperature <37.8 degrees C < or = 24 hours after dosing, plus a > or = 50% reduction in symptom score by 36 hours), early resolvers (temperature <37.8 degrees C < or = 36 hours after dosing), and nonaccelerated resolvers (febrile >36 hours after dosing). Patients in the accelerated and early categories were termed rapid resolvers; the others were slow resolvers. Patients recorded their symptom severity, temperature, ability to perform normal daily activities, and use of relief medication on a diary card. The primary end point of median time to alleviation of symptoms was also reexamined, with the additional requirement that patients were not taking relief medication when their symptoms were alleviated. This analysis was intended to control for the possible effect of relief medication on the primary end point.


RESULTS
In the influenza-positive population (n = 1572), significantly more zanamivir-treated patients were rapid resolvers compared with those receiving placebo (807 [72%] vs 765 [64%], P < 0.001). Significant benefits of zanamivir treatment were observed in patients with a baseline temperature of > or = 37.8 degrees C (630 [68%] vs 595 [57%], P < 0.001) or > or = 38.3 degrees C (382 [67%] vs 365 [52%], P < 0.001) and in patients considered by their physi- cian to have severe symptoms at the start of therapy (252 [70%] vs 222 [63%], P = 0.02). Differences were even more apparent in patients with high-risk conditions (74% vs 53%, P = 0.014) and in those aged > or = 50 years (70% vs 54%, P = 0.005). Zanamivir treatment was also associated with a significant reduction in time to alleviation of symptoms with no use of relief medication. This was particularly noticeable in those aged > or = 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 zanamivir and those receiving placebo.


CONCLUSIONS
Zanamivir is more effective than placebo in patients with influenza at providing early symptom relief and a reduced duration of illness at a time when use of relief medication has ended. These benefits are seen across different patient groups but appear to be particularly marked in patients who are aged > or = 50 years, who have underlying illnesses, who are considered high risk, or who are more severely ill at the beginning of therapy.
Monto
A S
AS
Department of Epidemiology, University of Michigan School of Public Health, Ann Arhor, USA. asmonto@umich.edu
Moult
A B
AB
Sharp
S J
SJ
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006146:Guanidines; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D011714:Pyrans; D016032:Randomized Controlled Trials as Topic; D012794:Sialic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D053243:Zanamivir
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D009439:Neuraminidase; D053243:Zanamivir