Efficacy and Safety of Inhaled Zanamivir
Efficacy and Safety of Inhaled Zanamivir
Background: Influenza in patients with asthma can cause acute exacerbation and in patients with chronic obstructive pulmonary disease (COPD) it can lead to respiratory distress. Zanamivir is an effective treatment for both influenza A and B. However, controlled studies with zanamivir specifically in asthma or COPD patients with influenza illness are limited.
Objective: To investigate the clinical efficacy and safety of inhaled zanamivir for the treatment of influenza in patients with asthma or COPD. Design and Setting: This randomised, double-blind, placebo-controlled, multicentre study was conducted at 159 sites in 15 countries.
Patients and Participants: 525 patients with asthma or COPD aged ≥12 years and with influenza-like illness were enrolled; 313 (60%) of these had laboratory-confirmed influenza virus infection and were included in the primary efficacy analysis.
Methods: Patients were randomised to inhaled zanamivir 10mg or matching placebo via Diskhaler twice daily for 5 days. Patients recorded symptoms and pulmonary function twice daily in diary cards. The primary end-point in both patient groups was time to alleviation of symptoms of influenza.
Results: Zanamivir significantly reduced the median time to alleviation of influenza symptoms compared with placebo (5.5 days vs7.0 days; difference 1.5 days; 95% confidence interval 0.50 to 3.25 days; p = 0.009). Zanamivir significantly reduced the mean overall influenza assessment score compared with placebo (p = 0.004) over days 1 to 5. Patients recorded fewer nights of sleep disturbance with zanamivir compared with placebo (median 2 nights vs3 nights; p = 0.042) during treatment. Zanamivir reduced the incidence of complications (requiring antibiotics and a change in respiratory medication) compared with placebo by 58% (p = 0.064). Zanamivir did not adversely affect pulmonary function, as determined by measurements of forced expiratory volume in 1 second and peak expiratory flow rate, compared with placebo. Zanamivir was well tolerated, with a safety profile similar to placebo. Compliance with treatment was high, with 495 (94%) patients successfully completing at least 4 days of treatment (8 doses). Furthermore, 90% of patients felt that the Diskhaler was easy or very easy to use.
Conclusion: Zanamivir is an effective treatment for influenza in patients with asthma or COPD, and has a safety profile similar to that of placebo. Importantly, zanamivir does not adversely affect pulmonary function in this high-risk population.
Influenza outbreaks occur mainly during the winter months and are responsible for serious morbidity and increased mortality. In epidemic years influenza infection rates can vary from 10 to 20%of the general population. The elderly or the immunocompromised and those with underlying diseases, such as chronic respiratory disease, cardiovascular disease and diabetes, are especially at risk of developing influenza-related complications. In these patients, influenza can exacerbate underlying medical conditions or lead to secondary bacterial pneumonia or primary influenza viral pneumonia. In the USA, hospitalisation rates due to acute respiratory disease during influenza epidemics are about 197/100 000 for persons with high-risk conditions compared with 93/100 000 for persons without. The highest rates of hospitalisation occur among those over 65 years of age with pulmonary conditions (875/100 000). Influenza-related mortality is low in otherwise healthy adults aged between 45 and 64 years (about 2/100 000), but can increase to 870/100 000 in those with underlying cardiovascular and pulmonary disease. In recent influenza epidemics, approximately 80 to 90% of the excess mortality occurred in those over 64 years of age.
Individuals deemed at high risk of developing influenza-related complications are recommended for annual vaccination against influenza. Despite the proven efficacy of influenza vaccines, less than 30% of those who were younger than 65 years and at high risk were vaccinated in the USA in 1997. Of particular concern is that less than 10 to 15% of patients with chronic lung disease such as asthma are vaccinated. Furthermore, the efficacy of vaccination may be limited by several factors such as patient's age, immunocompetence, timing of vaccination, and the degree of similarity between the vaccine and the circulating influenza strain.
The antiviral agents amantadine and rimantadine have been available for over 20 years for the prophylaxis and treatment of influenza. However, they are not effective against influenza B and their use has not gained wide acceptance due in part to the rapid emergence of drug-resistant variants and a poor adverse event profile. In addition, it is uncertain whether amantadine or rimantadine are beneficial in treating severe influenza infections or in preventing complications.
Zanamivir is the first specific influenza virus neuraminidase inhibitor, with a potent inhibitory activity against both influenza A and B viruses. It is an orally inhaled agent that is delivered directly to the primary site of viral replication: the respiratory tract. Treatment with zanamivir is well tolerated and has not been associated with the development of viral resistance in clinical trials to date. Studies have shown that zanamivir significantly shortens the time to alleviation of the symptoms of influenza A and B infection by up to 2.5 days. A recent pooled analysis of the efficacy of zanamivir in high-risk patients suggested that these patients derive a similar degree of benefit from zanamivir treatment; zanamivir shortened the time to alleviation of the symptoms of influenza A and B infection by 2.5 days compared with placebo. In addition, zanamivir reduced the incidence of influenza-related complications requiring treatment with antibiotics by 43% compared with placebo.
Respiratory viral infections are implicated as a significant cause of acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Patients with asthma or COPD are at greater risk of developing influenza-related complications because their airways are already compromised. In a prospective study, influenza virus was isolated from 19% of patients hospitalised following an acute exacerbation of their asthma. In particular, influenza infection can induce asthma exacerbation in 75 to 100% of children aged 8 to 16 years. With an estimated global burden of asthma of the order of 130 million people, effective treatment of influenza infections in this population is needed. Patients with asthma or COPD are not precluded from treatment with zanamivir, but precautions for use in these patients were added to the product labelling following rare post-marketing reports of bronchospasm and reduced lung function in patients using zanamivir. In otherwise healthy patients with mild or moderate asthma, inhaled zanamivir was well tolerated and did not significantly affect pulmonary function and airway responsiveness. High-risk patients treated with inhaled zanamivir had reduced influenza-related complications without increased risk for asthma exacerbation or increased asthma symptoms.
Controlled studies with zanamivir specifically in asthma or COPD patients with influenza illness are limited. We therefore investigated the efficacy and safety of zanamivir in the treatment of influenza A and B infection in patients diagnosed with asthma or COPD.
Background: Influenza in patients with asthma can cause acute exacerbation and in patients with chronic obstructive pulmonary disease (COPD) it can lead to respiratory distress. Zanamivir is an effective treatment for both influenza A and B. However, controlled studies with zanamivir specifically in asthma or COPD patients with influenza illness are limited.
Objective: To investigate the clinical efficacy and safety of inhaled zanamivir for the treatment of influenza in patients with asthma or COPD. Design and Setting: This randomised, double-blind, placebo-controlled, multicentre study was conducted at 159 sites in 15 countries.
Patients and Participants: 525 patients with asthma or COPD aged ≥12 years and with influenza-like illness were enrolled; 313 (60%) of these had laboratory-confirmed influenza virus infection and were included in the primary efficacy analysis.
Methods: Patients were randomised to inhaled zanamivir 10mg or matching placebo via Diskhaler twice daily for 5 days. Patients recorded symptoms and pulmonary function twice daily in diary cards. The primary end-point in both patient groups was time to alleviation of symptoms of influenza.
Results: Zanamivir significantly reduced the median time to alleviation of influenza symptoms compared with placebo (5.5 days vs7.0 days; difference 1.5 days; 95% confidence interval 0.50 to 3.25 days; p = 0.009). Zanamivir significantly reduced the mean overall influenza assessment score compared with placebo (p = 0.004) over days 1 to 5. Patients recorded fewer nights of sleep disturbance with zanamivir compared with placebo (median 2 nights vs3 nights; p = 0.042) during treatment. Zanamivir reduced the incidence of complications (requiring antibiotics and a change in respiratory medication) compared with placebo by 58% (p = 0.064). Zanamivir did not adversely affect pulmonary function, as determined by measurements of forced expiratory volume in 1 second and peak expiratory flow rate, compared with placebo. Zanamivir was well tolerated, with a safety profile similar to placebo. Compliance with treatment was high, with 495 (94%) patients successfully completing at least 4 days of treatment (8 doses). Furthermore, 90% of patients felt that the Diskhaler was easy or very easy to use.
Conclusion: Zanamivir is an effective treatment for influenza in patients with asthma or COPD, and has a safety profile similar to that of placebo. Importantly, zanamivir does not adversely affect pulmonary function in this high-risk population.
Influenza outbreaks occur mainly during the winter months and are responsible for serious morbidity and increased mortality. In epidemic years influenza infection rates can vary from 10 to 20%of the general population. The elderly or the immunocompromised and those with underlying diseases, such as chronic respiratory disease, cardiovascular disease and diabetes, are especially at risk of developing influenza-related complications. In these patients, influenza can exacerbate underlying medical conditions or lead to secondary bacterial pneumonia or primary influenza viral pneumonia. In the USA, hospitalisation rates due to acute respiratory disease during influenza epidemics are about 197/100 000 for persons with high-risk conditions compared with 93/100 000 for persons without. The highest rates of hospitalisation occur among those over 65 years of age with pulmonary conditions (875/100 000). Influenza-related mortality is low in otherwise healthy adults aged between 45 and 64 years (about 2/100 000), but can increase to 870/100 000 in those with underlying cardiovascular and pulmonary disease. In recent influenza epidemics, approximately 80 to 90% of the excess mortality occurred in those over 64 years of age.
Individuals deemed at high risk of developing influenza-related complications are recommended for annual vaccination against influenza. Despite the proven efficacy of influenza vaccines, less than 30% of those who were younger than 65 years and at high risk were vaccinated in the USA in 1997. Of particular concern is that less than 10 to 15% of patients with chronic lung disease such as asthma are vaccinated. Furthermore, the efficacy of vaccination may be limited by several factors such as patient's age, immunocompetence, timing of vaccination, and the degree of similarity between the vaccine and the circulating influenza strain.
The antiviral agents amantadine and rimantadine have been available for over 20 years for the prophylaxis and treatment of influenza. However, they are not effective against influenza B and their use has not gained wide acceptance due in part to the rapid emergence of drug-resistant variants and a poor adverse event profile. In addition, it is uncertain whether amantadine or rimantadine are beneficial in treating severe influenza infections or in preventing complications.
Zanamivir is the first specific influenza virus neuraminidase inhibitor, with a potent inhibitory activity against both influenza A and B viruses. It is an orally inhaled agent that is delivered directly to the primary site of viral replication: the respiratory tract. Treatment with zanamivir is well tolerated and has not been associated with the development of viral resistance in clinical trials to date. Studies have shown that zanamivir significantly shortens the time to alleviation of the symptoms of influenza A and B infection by up to 2.5 days. A recent pooled analysis of the efficacy of zanamivir in high-risk patients suggested that these patients derive a similar degree of benefit from zanamivir treatment; zanamivir shortened the time to alleviation of the symptoms of influenza A and B infection by 2.5 days compared with placebo. In addition, zanamivir reduced the incidence of influenza-related complications requiring treatment with antibiotics by 43% compared with placebo.
Respiratory viral infections are implicated as a significant cause of acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Patients with asthma or COPD are at greater risk of developing influenza-related complications because their airways are already compromised. In a prospective study, influenza virus was isolated from 19% of patients hospitalised following an acute exacerbation of their asthma. In particular, influenza infection can induce asthma exacerbation in 75 to 100% of children aged 8 to 16 years. With an estimated global burden of asthma of the order of 130 million people, effective treatment of influenza infections in this population is needed. Patients with asthma or COPD are not precluded from treatment with zanamivir, but precautions for use in these patients were added to the product labelling following rare post-marketing reports of bronchospasm and reduced lung function in patients using zanamivir. In otherwise healthy patients with mild or moderate asthma, inhaled zanamivir was well tolerated and did not significantly affect pulmonary function and airway responsiveness. High-risk patients treated with inhaled zanamivir had reduced influenza-related complications without increased risk for asthma exacerbation or increased asthma symptoms.
Controlled studies with zanamivir specifically in asthma or COPD patients with influenza illness are limited. We therefore investigated the efficacy and safety of zanamivir in the treatment of influenza A and B infection in patients diagnosed with asthma or COPD.