Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma.
BACKGROUND
Anti-leukotriene (AL) agents are being considered as "add-on" therapy to inhaled corticosteroids (ICS), in chronic asthma.


OBJECTIVE
To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid-sparing effect of AL when added to ICS in chronic asthma.


METHODS
We searched Medline, Embase, Cinahl (until September 2001), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and ATS meeting abstracts (1998-2000).


METHODS
Randomised placebo-controlled trials of asthmatics aged 2 years and older with at least one month intervention.


METHODS
Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well-controlled) and dose of ICS in the control group (same or double).


RESULTS
Of 438 citations, 13 (12 adult and 1 paediatric) trials met inclusion criteria. Seven were published in full-text. In symptomatic patients, addition of licensed doses of anti-leukotrienes to ICS resulted in a non-significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.61; 95% Confidence Interval (CI) 0.36,1.05). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.71 L/min; 95%CI 2.98, 12.44 L/min) together with beta2-agonist use (WMD= -0.32 puffs/day; 95%CI -0.0.08, -0.56). No trials that compared the use of licensed doses of anti-leukotrienes with doubling-dose of inhaled glucocorticoids could be pooled. In ICS-sparing studies in patients who were well controlled at baseline, addition of anti-leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD -44.4 mcg/d, 95%CI -147.9, 59.0 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR= 0.56, 95%CI 0.35, 0.89).


CONCLUSIONS
There is insufficient evidence to firmly support the use of licensed doses of anti-leukotrienes as add-on therapy to inhaled glucocorticoids. Addition of anti-leukotrienes to inhaled glucocorticoids may slightly improve asthma control, but the available data do not permit this strategy to be recommended as a substitute for increasing the dose of inhaled glucocorticoids. Addition of anti-leukotrienes may be associated with superior asthma control after glucocorticoid tapering, but a glucocorticoid-sparing effect cannot be quantified at present.
Ducharme
F
F
Pediatrics and Epidemiology & Biostatistics, McGill University Health Centre, Montreal Chidren's Hospital, 2300 Tupper Street, Room C-538E, Montreal, Quebec, Canada, H3H 1P3. francine.ducharme@muhc.mcgill.ca
Hicks
G
G
Kakuma
R
R
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D013256:Steroids
D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D020024:Leukotriene Antagonists; D013256:Steroids