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FOCUS ON PULMONARY
DISORDERS Devra K. Dang, Section
Advisor
Inhaled corticosteroids: Risks outweigh benefit in COPD
Key point: The benefit of adding an inhaled
corticosteroid (ICS) to a long-acting beta-2 agonist (LABA) in patients
with chronic obstructive pulmonary disease (COPD) is limited; serious
risks including increased incidence of pneumonia and other infections
exist.
Finer points: This large systematic review, which
was recently published in Chest, compared the safety and efficacy of
combination therapy (ICS plus LABA) to monotherapy with LABA. The
following inclusion criteria were used: (1) stable adult patients older
than 40 years with COPD; (2) therapy with LABA plus ICS as the
intervention arm, compared with monotherapy with LABA; (3) study
duration longer than 1 month; (4) randomized, controlled trial; and (5)
primary out-comes being severe COPD exacerbation, defined as requiring
hospitalization or withdrawal, and moderate COPD exacer-bation, defined
as requiring systemic corticosteroids or antibiotic use; and examining
all-cause mortality, respiratory deaths, and cardiovascular mortality
during the treatment period. Secondary outcomes included mean change in
forced expiratory volume in 1 second (FEV1), mean change from baseline
in St. George respiratory questionnaire total score, end-of-treatment
dyspnea score, withdrawals, and adverse events.
A total of 18 randomized, controlled clinical trials involving 12,446
stable patients with moderate to severe COPD were identified using
Medline, EMBASE (January 1980–May 2009), and the Cochrane
Controlled Trials Register. In the pooled analysis, combination therapy
was associated with a significantly reduced risk of moderate COPD
exacerbations compared with monotherapy with LABA (17.5% vs. 20.1%,
respectively), with evidence of statistical heterogeneity among trials.
The number needed to treat for benefit was 31 (95% CI 20–93).
However, no significant differences were observed between groups with
the other primary outcomes (severe COPD exacerbation, overall mortality,
risk of respiratory death, and car-diovascular mortality).
Compared with LABA monotherapy, combination therapy produced
significantly greater increases in mean change in FEV1 from baseline,
end-of-treatment dyspnea scores, and health-related quality-of-life
scores; however, according to the authors, “the size of these
benefits did not reach the suggested clinically important minimal
differences.” Of greatest concern, combination therapy was
associated with significant increases in pneumonia (63% increase in
relative risk [RR]), viral respiratory infections (22% increase in RR),
and oropharyngeal candidiasis (59% increase in RR) compared with
monotherapy with LABA.
What you need to know: Current guidelines recommend
using combination therapy for patients with severe and very severe COPD.
This analysis shows that the relative benefits of combination therapy
must be weighed against the risks. Future definitions of different COPD
phenotypes may allow clinicians to better understand which patients will
most benefit from combination therapy.
The authors noted that the primary limitations to the study came from
the quality of the reported data. The trials did not use consistent
definitions of COPD exacerbation or pneumonia. In addition, the majority
of the studies were not de-signed to evaluate outcomes such as
all-cause, respiratory, or cardiovascular mortality. The risk of bias
was unclear in 13 of the 18 trials included in the meta-analysis.
Finally, the fact that 80% of patients in the studies were men limits
the ability to generalize the results, because historical data suggest
that COPD affects men and women equally.
What your patients need to know: Tell patients that
most people with COPD only need treatment with a long-acting inhaled
bronchodilator (either LABA or tiotropium), at least until future
research identifies which patients are most likely to benefit from
combination therapy.
Source:
Related resource on www.pharmacist.com
Beth Farnstrom (bfarnstrom@aphanet.org)
Posted November 17, 2009
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