Moxifloxacin in Acute Exacerbations of Chronic Bronchitis
Moxifloxacin in Acute Exacerbations of Chronic Bronchitis
This non-interventional, naturalistic observational study enrolled a large cohort of outpatients (n = 2672) with AECB, Anthonisen types I to III, to receive moxifloxacin treatment at the recommended dose of 400 mg once daily. A special feature of the study is the well-documented patient history regarding previous AECBs, concomitant diseases, and comedications related both to the underlying respiratory disease as well as to other comorbidities before study entry. The majority of patients (approximately 80%) had experienced an exacerbation within the previous 12 months. Also reflecting current clinical experience, a large proportion of the patients had an underlying respiratory condition (e.g. COPD, emphysema, or asthma).
Moxifloxacin administered for a mean of 6.4 days (range 1–15 days) was a highly effective treatment in these patients. Individual symptoms and signs of sputum volume, fever, cough, dyspnea, and sputum character resolved or improved in the majority of patients (range 77–89%) during the observational period. Improvements in symptoms occurred after a mean of 3.4 days and over 93% of patients were symptom-free after 10 days. No differences in the efficacy of moxifloxacin were observed between patients either without or with a diverse range of comorbidities.
Unlike in clinical trials, the dosing regimen used in this non-interventional study was left to the sole discretion of the treating physician. It is interesting to note the high rate of physician compliance (99.6%) with the dose recommended in the Summary of Product Characteristics. This suggests that physicians considered the recommended dose of moxifloxacin to be highly effective, without the need to adjust the dose, e.g. for body weight. The lack of need for dose adjustment has the advantages of easier dosing and a reduced risk of overdosing.
The results of this study are in agreement with previous studies of moxifloxacin treatment in patients with AECB, including the international observational GIANT study, where symptom improvement occurred after a mean of 3.4 days. Physicians' summary assessments of moxifloxacin were also similar in the two studies, including a rating of 'very good or good' in excess of 95% of patients.
The rapid recovery from symptoms observed in this study is a desirable characteristic of an effective treatment for patients with AECB. Other observational and controlled studies and cross-sectional analyses report that moxifloxacin is associated with a more rapid recovery from symptoms than other commonly used treatments. The mean duration of treatment until symptom improvement in the current study was broadly similar among patients, but with a trend to increased treatment duration in patients with greater AECB severity, concomitant diseases, and older age.
Physicians rated the tolerability of moxifloxacin as 'very good or good' in approximately 98% of patients, similar to the rate (97%) reported in the observational study by Miravitlles et al.. Incidences of TEAEs and drug-related adverse events were low. The incidence of TEAEs was lower in the current study than reported in controlled clinical studies (e.g.), which may be attributed to an underreporting of mild/moderate adverse events that is a feature of observational studies.
The profile of adverse events reported in this study is in agreement with current knowledge of this antibiotic. A meta-analysis of clinical trial and post-marketing surveillance data for moxifloxacin identified nausea, dizziness, and diarrhea as the most frequent adverse events, which occurred at a rate similar to comparator medications. For most patients in the current study, adverse events resolved during the course of treatment and were associated with low rates of treatment withdrawal (0.4%). The observational study by Miravitlles et al. reported similarly low rates of treatment-related withdrawal (0.6%).
The overall satisfaction with moxifloxacin treatment expressed by both physicians and patients was high. Relative to previous antibiotics, moxifloxacin also provided a superior efficacy and a faster onset of effect in the majority of patients.
Notable demographic and disease characteristics of this population from South Eastern/Eastern Europe include a markedly higher incidence of COPD among non-smokers when compared with data from Western Europe and the USA. This indicates that additional environmental factors, such as high levels of industrial air pollution and/or occupational or home indoor air pollution, contributed to the development of COPD in patients from the participating countries, as described by Mannino and Buist.
Limitations of the current study include the primary role of physician judgment for decisions on patient selection and management; the absence of a control group to quantify the response to other antibacterial agents; and the lack of bacteriological assessment, which precludes a correlation with the clinical outcomes. All prescribing choices were made by physicians. As approximately 16% of patients who received moxifloxacin were classified with Anthonisen type III AECB, antibiotic therapy was not prescribed in accordance with current guidelines in all circumstances. A similar experience was reported in the GIANT study.
A strength of observational studies is that they provide an important accompaniment to randomized controlled trials and reflect real-world practice in terms of prescribing behavior. The lack of bacteriological assessment in this study is in line with current practice for the outpatient treatment of AECB. The high response rate in this study, which included patients with a range of common comorbidities, suggests that treatment with broader-spectrum drugs such as moxifloxacin is appropriate for patients with moderate-to-severe AECB who are managed outside hospital.
Discussion
This non-interventional, naturalistic observational study enrolled a large cohort of outpatients (n = 2672) with AECB, Anthonisen types I to III, to receive moxifloxacin treatment at the recommended dose of 400 mg once daily. A special feature of the study is the well-documented patient history regarding previous AECBs, concomitant diseases, and comedications related both to the underlying respiratory disease as well as to other comorbidities before study entry. The majority of patients (approximately 80%) had experienced an exacerbation within the previous 12 months. Also reflecting current clinical experience, a large proportion of the patients had an underlying respiratory condition (e.g. COPD, emphysema, or asthma).
Moxifloxacin administered for a mean of 6.4 days (range 1–15 days) was a highly effective treatment in these patients. Individual symptoms and signs of sputum volume, fever, cough, dyspnea, and sputum character resolved or improved in the majority of patients (range 77–89%) during the observational period. Improvements in symptoms occurred after a mean of 3.4 days and over 93% of patients were symptom-free after 10 days. No differences in the efficacy of moxifloxacin were observed between patients either without or with a diverse range of comorbidities.
Unlike in clinical trials, the dosing regimen used in this non-interventional study was left to the sole discretion of the treating physician. It is interesting to note the high rate of physician compliance (99.6%) with the dose recommended in the Summary of Product Characteristics. This suggests that physicians considered the recommended dose of moxifloxacin to be highly effective, without the need to adjust the dose, e.g. for body weight. The lack of need for dose adjustment has the advantages of easier dosing and a reduced risk of overdosing.
The results of this study are in agreement with previous studies of moxifloxacin treatment in patients with AECB, including the international observational GIANT study, where symptom improvement occurred after a mean of 3.4 days. Physicians' summary assessments of moxifloxacin were also similar in the two studies, including a rating of 'very good or good' in excess of 95% of patients.
The rapid recovery from symptoms observed in this study is a desirable characteristic of an effective treatment for patients with AECB. Other observational and controlled studies and cross-sectional analyses report that moxifloxacin is associated with a more rapid recovery from symptoms than other commonly used treatments. The mean duration of treatment until symptom improvement in the current study was broadly similar among patients, but with a trend to increased treatment duration in patients with greater AECB severity, concomitant diseases, and older age.
Physicians rated the tolerability of moxifloxacin as 'very good or good' in approximately 98% of patients, similar to the rate (97%) reported in the observational study by Miravitlles et al.. Incidences of TEAEs and drug-related adverse events were low. The incidence of TEAEs was lower in the current study than reported in controlled clinical studies (e.g.), which may be attributed to an underreporting of mild/moderate adverse events that is a feature of observational studies.
The profile of adverse events reported in this study is in agreement with current knowledge of this antibiotic. A meta-analysis of clinical trial and post-marketing surveillance data for moxifloxacin identified nausea, dizziness, and diarrhea as the most frequent adverse events, which occurred at a rate similar to comparator medications. For most patients in the current study, adverse events resolved during the course of treatment and were associated with low rates of treatment withdrawal (0.4%). The observational study by Miravitlles et al. reported similarly low rates of treatment-related withdrawal (0.6%).
The overall satisfaction with moxifloxacin treatment expressed by both physicians and patients was high. Relative to previous antibiotics, moxifloxacin also provided a superior efficacy and a faster onset of effect in the majority of patients.
Notable demographic and disease characteristics of this population from South Eastern/Eastern Europe include a markedly higher incidence of COPD among non-smokers when compared with data from Western Europe and the USA. This indicates that additional environmental factors, such as high levels of industrial air pollution and/or occupational or home indoor air pollution, contributed to the development of COPD in patients from the participating countries, as described by Mannino and Buist.
Limitations of the current study include the primary role of physician judgment for decisions on patient selection and management; the absence of a control group to quantify the response to other antibacterial agents; and the lack of bacteriological assessment, which precludes a correlation with the clinical outcomes. All prescribing choices were made by physicians. As approximately 16% of patients who received moxifloxacin were classified with Anthonisen type III AECB, antibiotic therapy was not prescribed in accordance with current guidelines in all circumstances. A similar experience was reported in the GIANT study.
A strength of observational studies is that they provide an important accompaniment to randomized controlled trials and reflect real-world practice in terms of prescribing behavior. The lack of bacteriological assessment in this study is in line with current practice for the outpatient treatment of AECB. The high response rate in this study, which included patients with a range of common comorbidities, suggests that treatment with broader-spectrum drugs such as moxifloxacin is appropriate for patients with moderate-to-severe AECB who are managed outside hospital.