Authors' objectives

To investigate whether inhaled corticosteroids (ICS) exhibit a dose-response relationship in the treatment of mild to moderate persistent asthma.

Searching

PubMed and MEDLINE were searched from January 1996 to January 2001 using the following search terms: 'asthma' and 'corticosteroids', 'glucocorticoids', 'beclomethasone', 'budesonide', 'fluticasone', 'flunisolide', 'mometasone' or 'triamcinolone acetonide'. The reference lists of the articles were also examined for other publications.

Study selection

Assessment of study quality

The authors do not state that they assessed validity.

Data extraction

Two reviewers independently extracted the data. Detailed information on the clinical trials of interest was extracted from documents obtained from the US Food and Drug Administration. When relevant data could not be found, additional data were requested from the authors of the primary studies. The information tabulated in the review included: study identification, washout period, duration of treatment, doses, device (type of inhaler), number of patients, mean age, asthma severity, FEV1 cutoff, mean FEV1, and outcome data.

Methods of synthesis

Results of the review

Sixteen RCTs with 4,703 participants were included in the review. There were 8 trials (n=2,227) of fluticasone propionate, 3 (n=1,337) of triamcinolone acetonide, 3 (n=597) of budesonide, and 2 (n=542) of mometasone furoate.

A statistically-significant dose response in am PEFR was observed with fluticasone propionate (95% confidence interval, CI: 4.9, 11.5), triamcinolone acetonide (95% CI: 4.7, 18.0) and budesonide (95% CI: 5.8, 24.9). A statistically-significant dose response to fluticasone propionate and triamcinolone acetonide was also observed in pm PEFR (95% CI: 2.0, 8.7 and 95% CI: 2.4, 13.7, respectively) and asthma symptom score (95% CI: -0.069, -0.002 and 95% CI: -0.60, -0.10, respectively). In terms of FEV1, the dose response was only statistically significant with budesonide (95% CI: 0.025, 0.17).

The relationships generally remained significant when analyses omitting the highest dose were conducted; the exception being the dose response in pm PEFR with fluticasone propionate, which was not significant.

Authors' conclusions

Dose-response relationships were not uniformly observed with all of the drugs or for all of the response measures. Outcome measures, particularly am and pm PEFR, and to a lesser extent, FEV1, were sensitive to the dose of ICS. However, this effect was driven mainly by ICS doses below or at the low end of the recommended ranges, and not by the highest doses. The use of higher doses of ICS in patients with mild to moderate persistent asthma did not appear to increase the efficacy of these drugs.

CRD commentary

The review question and the inclusion and exclusion criteria were clearly stated. The authors searched MEDLINE and PubMed, which are almost identical, but do not appear to have searched for unpublished data. In addition, they do not state whether any language restrictions were applied, or justify why their search dates were relatively narrow. Thus, it is possible that some studies may have been missed, introducing retrieval bias. The validity of the individual studies does not appear to have been assessed.

The authors state that eligible studies were independently extracted by two reviewers. Sufficient details of the individual studies were tabulated, and the studies were summarised appropriately using a meta-regression. However, the authors' conclusions presented in the abstract could have provided more information to clearly reflect the results and conclusions presented in the paper, i.e. where dose-response relationships exist (increasing the dose beyond a threshold value may provide little additional benefit in the alleviation of asthma symptoms).

The conclusions (as presented in the paper) appear to follow the results, but would be strengthened by including an assessment of the quality of the studies.

Implications of the review for practice and research

Practice: The authors state that therapeutic benefits can be maximised and adverse effects minimised by using the lowest effective ICS dose.

Research: The authors did not state any implications for further research.

Funding

Worldwide Outcomes Research, Merck and Co, Inc.

Bibliographic details

Bousquet J, Ben-Joseph R, Messonnier M, Alemao E, Gould A L. A meta-analysis of the dose-response relationship of inhaled corticosteroids in adolescents and adults with mild to moderate persistent asthma. Clinical Therapeutics 2002; 24(1): 1-20. [PubMed: 11833824]

Indexing Status

Subject indexing assigned by NLM

MeSH

Administration, Inhalation; Adolescent; Adrenal Cortex Hormones /administration & dosage /therapeutic use; Adult; Algorithms; Anti-Asthmatic Agents /administration & dosage /therapeutic use; Asthma /drug therapy /pathology /physiopathology; Dose-Response Relationship, Drug; Humans; Randomized Controlled Trials as Topic; Respiratory Function Tests; Treatment Outcome

AccessionNumber

12002008139

Database entry date

31/01/2003

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.