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Jonas DE, Wines RCM, DelMonte M, et al. Drug Class Review: Controller Medications for Asthma: Final Update 1 Report [Internet]. Portland (OR): Oregon Health & Science University; 2011 Apr.

Cover of Drug Class Review: Controller Medications for Asthma

Drug Class Review: Controller Medications for Asthma: Final Update 1 Report [Internet].

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Summary

Strength of Evidence (SOE)

The main results of this review are summarized in Table 31. Summaries of the strength of evidence (SOE) for each comparison are presented in Appendix H. Efficacy studies provide moderate strength of evidence (SOE) that equipotent doses of ICSs administered through comparable delivery devices do not differ in their ability to control asthma symptoms, prevent exacerbations, reduce the need for additional rescue medication, or in the overall incidence of adverse events or withdrawals due to adverse events. Evidence does not support a difference between montelukast and zafirlukast in their ability to decrease rescue medicine use or improve quality of life (low SOE for ≥ 12 years of age, insufficient <12), or between formoterol and salmeterol in their ability to control symptoms, prevent exacerbations, improve quality of life, or cause harms among patients not controlled on ICSs alone (moderate SOE). Evidence does not support a difference between budesonide/formoterol and fluticasone/salmeterol for efficacy or harms when each combination is administered via a single inhaler (moderate SOE for ≥ 12, insufficient <12).

Table 31. Summary of the evidence by key question for controller medications for the treatment of persistent asthma in adolescents/adults ≥ 12 years of age and children < 12 years of age.

Table 31

Summary of the evidence by key question for controller medications for the treatment of persistent asthma in adolescents/adults ≥ 12 years of age and children < 12 years of age.

Meta-analyses and efficacy studies provide consistent evidence favoring omalizumab over placebo for the ability to control asthma symptoms, prevent exacerbations, and reduce the need for additional rescue medication. Omalizumab-treated patients have an increased incidence of injection site reactions and anaphylaxis compared to placebo-treated patients.

Efficacy studies up to 56 weeks in duration provide consistent evidence of greater benefit for subjects treated with ICS monotherapy compared with those treated with LM monotherapy (high SOE). Direct evidence suggests no difference in tolerability or overall adverse events between ICSs and LMs (moderate SOE). Specific adverse events reported with ICSs, such as cataracts and decreased growth velocity, were not found among patients taking LMs. The best longer-term evidence on growth (avg 4.3 years) is from the CAMP study, which found a 1.1cm difference in mean increase in height (P = 0.005) between BUD and placebo-treated patients. The differences in growth occurred primarily during the first year of treatment, suggesting that the small decrease in growth velocity with ICSs occurs early in treatment and is not progressive. Evidence is insufficient to determine if long-term treatment with ICSs leads to a reduction in final adult height. Overall evidence indicates that ICSs and leukotriene receptor antagonists (LTRAs) are safer than LABAs for use as monotherapy (high SOE). LABAs are not recommended nor approved for use as monotherapy for persistent asthma because they may increase the risk of asthma-related deaths. Indirect evidence suggests that the potential increased risk of asthma-related death for those taking LABAs may be confined to patients not taking ICSs at baseline.

Meta-analyses of results from large trials up to twelve months in duration found mixed results and do not provide sufficient evidence to support the routine use of combination therapy rather than an ICS alone as first line therapy (moderate SOE for ≥ 12, insufficient <12). Of note, FDA approved prescribing information and guidelines from the NAEPP suggest that combination therapy should only be used for patients not adequately controlled on a long-term asthma controller medication, such as an ICS, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Results from large trials up to twelve months in duration support greater efficacy with the addition of a LABA to an ICS than with a higher dose ICS (high SOE for ≥ 12, low <12). Results from large trials up to one year in duration support greater efficacy with the addition of a LABA to an ICS over continuing the current dose of ICS alone for poorly controlled persistent asthma (high SOE). The addition of LMs to ICSs compared to continuing the same dose of ICSs resulted in improvement in rescue medicine use and no statistically significant differences in other health outcomes (low SOE for ≥ 12, insufficient <12). There is no apparent difference in symptoms, exacerbations, rescue medicine use, overall adverse events, or withdrawals due to adverse events between those treated with ICSs plus LTRAs compared to those treated with increasing the dose of ICSs (moderate SOE for ≥ 12, low <12). Results provide strong evidence that the addition of a LABA to ICS therapy (ICS+LABA) is more efficacious than the addition of an LTRAs to ICS therapy (ICS+LTRA) (high SOE for ≥ 12, low <12). We found no difference in overall adverse events or withdrawals due to adverse events between ICS+LABA and ICS+ LTRAs (moderate SOE for ≥12, insufficient <12).

Limitations of this Report

As with other types of research, the limitations of this systematic review are important to recognize. These can be divided into 2 groups, those relating to applicability of the results (addressed below) and those relating to methodology within the scope of this review.

Methodological limitations of the review within the defined scope included the exclusion of studies published in languages other than English and lack of a specific search for unpublished studies. In addition, the data from RCTs included in this report have limited utility for assessing real-world adherence to medications. This is largely because they enrolled selected populations, often requiring a high degree of adherence to be included in the trial. For example, many of the trials had a run-in period during which adherence was assessed and then only included subjects that met a threshold for good adherence (e.g., adherence to 80% of recommended doses).

Unfortunately, for many drugs, there are few or no effectiveness studies and many efficacy studies. As a result, clinicians must make decisions about treatment for many patients who would not have been included in controlled trials and for whom the effectiveness and tolerability of the different drugs are uncertain. An evidence report indicates whether or not there is evidence that drugs differ in their effects in various subgroups of patients, but it does not attempt to set a standard for how results of controlled trials should be applied to patients who would not have been eligible for them. With or without an evidence report, these are decisions that must be informed by clinical judgment.

In the context of developing recommendations for practice, evidence reports are useful because they define the strengths and limits of the evidence, clarifying whether assertions about the value of the intervention are based on strong evidence from clinical studies. By themselves, they do not tell you what to do: Judgment, reasoning, and applying one’s values under conditions of uncertainty must also play a role in decision making. Users of an evidence report must also keep in mind that not proven does not mean proven not; that is, if the evidence supporting an assertion is insufficient, it does not mean the assertion is not true. The quality of the evidence on effectiveness is a key component, but not the only component, in making decisions about clinical policies. Additional criteria include acceptability to physicians or patients, the potential for unrecognized harms, the applicability of the evidence to practice, and consideration of equity and justice.

Applicability

The applicability of the results are limited by the scope of the Key Questions and inclusion criteria and by the applicability of the studies included. Most studies included narrowly defined populations of patients who met strict criteria for case definition, had few comorbidities, and used few or no concomitant medications. Minorities, older patients, and the most seriously ill patients were often under represented.

Studies Currently Being Conducted

We identified no trials in progress that would meet inclusion criteria for this review that would potentially change conclusions.

Copyright © 2011 by Oregon Health & Science University.
Bookshelf ID: NBK56684
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