Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children

Abstract

Background Anti-leukotrienes (5-lipoxygenase inhibitors and leukotriene receptors antagonists) serve as alternative monotherapy to inhaled corticosteroids (ICS) in the management of recurrent and/or chronic asthma in adults and children. Objectives To determine the safety and efficacy of anti-leukotrienes compared to inhaled corticosteroids as monotherapy in adults and children with asthma and to provide better insight into the influence of patient and treatment characteristics on the magnitude of effects. Search methods We searched MEDLINE (1966 to Dec 2010), EMBASE (1980 to Dec 2010), CINAHL (1982 to Dec 2010), the Cochrane Airways Group trials register, and the Cochrane Central Register of Controlled Trials (Dec 2010), abstract books, and reference lists of review articles and trials. We contacted colleagues and the international headquarters of anti-leukotrienes producers. Selection criteria We included randomised trials that compared anti-leukotrienes with inhaled corticosteroids as monotherapy for a minimum period of four weeks in patients with asthma aged two years and older. Data collection and analysis Two review authors independently assessed the methodological quality of trials and extracted data. The primary outcome was the number of patients with at least one exacerbation requiring systemic corticosteroids. Secondary outcomes included patients with at least one exacerbation requiring hospital admission, lung function tests, indices of chronic asthma control, adverse effects, withdrawal rates and biological inflammatory markers. Main results Sixty-five trials met the inclusion criteria for this review. Fifty-six trials (19 paediatric trials) contributed data (representing total of 10,005 adults and 3,333 children); 21 trials were of high methodological quality; 44 were published in full-text. All trials pertained to patients with mild or moderate persistent asthma. Trial durations varied from four to 52 weeks. The median dose of inhaled corticosteroids was quite homogeneous at 200 μg/day of microfine hydrofluoroalkane-propelled beclomethasone or equivalent (HFABDP eq). Patients treated with anti-leukotrienes were more likely to suffer an exacerbation requiring systemic corticosteroids (N = 6077 participants; risk ratio (RR) 1.51, 95% confidence interval (CI) 1.17, 1.96). For every 28 (95% CI 15 to 82) patients treated with anti-leukotrienes instead of inhaled corticosteroids, there was one additional patient with an exacerbation requiring rescue systemic corticosteroids. The magnitude of effect was significantly greater in patients with moderate compared with those with mild airway obstruction (RR 2.03, 95% CI 1.41, 2.91 versus RR 1.25, 95% CI 0.97, 1.61), but was not significantly influenced by age group (children representing 23% of the weight versus adults), anti-leukotriene used, duration of intervention, methodological quality, and funding source. Significant group differences favouring inhaled corticosteroids were noted in most secondary outcomes including patients with at least one e...

Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis

“…Conversely, study withdrawals, extracted as a proxy to adverse events, were more frequent in the montelukast group in five out of eight studies [ 38 – 40 , 46 , 48 ]. This result is consistent with another systematic review [ 24 ] which found that LTRA associated with a 24% increased risk of overall withdrawals in paediatric patients, but also with no statistically significant group difference due to adverse effects. Although treatment may occasionally be discontinued for mild or moderate adverse events, withdrawals are especially important because they reflect the ultimate decision of the participant and/or physician to discontinue treatment.…”

“…We found five systematic reviews evaluating the efficacy of montelukast or LTRA specifically on paediatric asthma patients [ 13 , 20 – 23 ], confirming the superiority of ICS in symptom control [ 20 , 21 , 24 ], symptom scores [ 13 ], symptom-free days [ 24 ], night-time awakening [ 24 ] and HRQoL [ 24 ]. Other systematic reviews compared LTRA with placebo [ 12 ], or as an addition to usual care [ 23 ].…”

Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis

“…Conversely, study withdrawals, extracted as a proxy to adverse events, were more frequent in the montelukast group in five out of eight studies [ 38 – 40 , 46 , 48 ]. This result is consistent with another systematic review [ 24 ] which found that LTRA associated with a 24% increased risk of overall withdrawals in paediatric patients, but also with no statistically significant group difference due to adverse effects. Although treatment may occasionally be discontinued for mild or moderate adverse events, withdrawals are especially important because they reflect the ultimate decision of the participant and/or physician to discontinue treatment.…”

“…We found five systematic reviews evaluating the efficacy of montelukast or LTRA specifically on paediatric asthma patients [ 13 , 20 – 23 ], confirming the superiority of ICS in symptom control [ 20 , 21 , 24 ], symptom scores [ 13 ], symptom-free days [ 24 ], night-time awakening [ 24 ] and HRQoL [ 24 ]. Other systematic reviews compared LTRA with placebo [ 12 ], or as an addition to usual care [ 23 ].…”

A Comparison of Confounding Adjustment Methods for Assessment of Asthma Controller Medication Effectiveness

“…Our finding that LTRAs may be just as effective as ICSs in preventing asthma-related exacerbations in real-life settings is contrary to the results of randomized clinical trials in which patients using ICSs were found to experience fewer asthma-related exacerbations than patients using LTRAs (15). One possible reason for our findings is that additional nonadherence beyond that adjusted for by the time-varying PDC played a role (13). Alternatively, persistent unmeasured confounding could also explain our results.…”

Questions in Mild Asthma: An Official American Thoracic Society Research Statement

“…A meta-analysis of six studies of mild asthma concluded that LTRAs plus SABA relievers reduced exacerbation risk and improved lung function compared with a SABA alone ( 99 ). However, LTRA efficacy was lower compared with that of regular low-dose ICS, as confirmed in Cochrane meta-analyses ( 100 ). In the LOCSS step-down trial in mild asthma, LTRAs showed higher rates of treatment failure compared with ICS regimens ( 97 ).…”

Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis

“…Conversely, study withdrawals, extracted as a proxy to adverse events, were more frequent in the montelukast group in five out of eight studies [ 38 – 40 , 46 , 48 ]. This result is consistent with another systematic review [ 24 ] which found that LTRA associated with a 24% increased risk of overall withdrawals in paediatric patients, but also with no statistically significant group difference due to adverse effects. Although treatment may occasionally be discontinued for mild or moderate adverse events, withdrawals are especially important because they reflect the ultimate decision of the participant and/or physician to discontinue treatment.…”

“…We found five systematic reviews evaluating the efficacy of montelukast or LTRA specifically on paediatric asthma patients [ 13 , 20 – 23 ], confirming the superiority of ICS in symptom control [ 20 , 21 , 24 ], symptom scores [ 13 ], symptom-free days [ 24 ], night-time awakening [ 24 ] and HRQoL [ 24 ]. Other systematic reviews compared LTRA with placebo [ 12 ], or as an addition to usual care [ 23 ].…”

A Comparison of Confounding Adjustment Methods for Assessment of Asthma Controller Medication Effectiveness

“…Our finding that LTRAs may be just as effective as ICSs in preventing asthma-related exacerbations in real-life settings is contrary to the results of randomized clinical trials in which patients using ICSs were found to experience fewer asthma-related exacerbations than patients using LTRAs (15). One possible reason for our findings is that additional nonadherence beyond that adjusted for by the time-varying PDC played a role (13). Alternatively, persistent unmeasured confounding could also explain our results.…”

Questions in Mild Asthma: An Official American Thoracic Society Research Statement

“…A meta-analysis of six studies of mild asthma concluded that LTRAs plus SABA relievers reduced exacerbation risk and improved lung function compared with a SABA alone ( 99 ). However, LTRA efficacy was lower compared with that of regular low-dose ICS, as confirmed in Cochrane meta-analyses ( 100 ). In the LOCSS step-down trial in mild asthma, LTRAs showed higher rates of treatment failure compared with ICS regimens ( 97 ).…”

Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis

“…Conversely, study withdrawals, extracted as a proxy to adverse events, were more frequent in the montelukast group in five out of eight studies [ 38 – 40 , 46 , 48 ]. This result is consistent with another systematic review [ 24 ] which found that LTRA associated with a 24% increased risk of overall withdrawals in paediatric patients, but also with no statistically significant group difference due to adverse effects. Although treatment may occasionally be discontinued for mild or moderate adverse events, withdrawals are especially important because they reflect the ultimate decision of the participant and/or physician to discontinue treatment.…”

“…We found five systematic reviews evaluating the efficacy of montelukast or LTRA specifically on paediatric asthma patients [ 13 , 20 – 23 ], confirming the superiority of ICS in symptom control [ 20 , 21 , 24 ], symptom scores [ 13 ], symptom-free days [ 24 ], night-time awakening [ 24 ] and HRQoL [ 24 ]. Other systematic reviews compared LTRA with placebo [ 12 ], or as an addition to usual care [ 23 ].…”

A Comparison of Confounding Adjustment Methods for Assessment of Asthma Controller Medication Effectiveness

“…Our finding that LTRAs may be just as effective as ICSs in preventing asthma-related exacerbations in real-life settings is contrary to the results of randomized clinical trials in which patients using ICSs were found to experience fewer asthma-related exacerbations than patients using LTRAs (15). One possible reason for our findings is that additional nonadherence beyond that adjusted for by the time-varying PDC played a role (13). Alternatively, persistent unmeasured confounding could also explain our results.…”

Questions in Mild Asthma: An Official American Thoracic Society Research Statement

“…A meta-analysis of six studies of mild asthma concluded that LTRAs plus SABA relievers reduced exacerbation risk and improved lung function compared with a SABA alone ( 99 ). However, LTRA efficacy was lower compared with that of regular low-dose ICS, as confirmed in Cochrane meta-analyses ( 100 ). In the LOCSS step-down trial in mild asthma, LTRAs showed higher rates of treatment failure compared with ICS regimens ( 97 ).…”