A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four.
BACKGROUND
The recommendations for the treatment of moderate persistent asthma in the Global Initiative for Asthma (GINA) guidelines for paediatric asthma are mainly based on scientific evidence extrapolated from studies in adults or on consensus. Furthermore, clinical decision-making would benefit from formal ranking of treatments in terms of effectiveness.Our objective is to assess all randomized trial-based evidence specifically pertaining to 5-18 year olds with moderate persistent asthma. Rank the different drug treatments of GINA guideline steps 3&4 in terms of effectiveness.


METHODS
Systematic review with network meta-analysis. After a comprehensive search in Central, Medline, Embase, CINAHL and the WHO search portal two reviewers selected RCTs performed in 4,129 children from 5-18 year old, with moderate persistent asthma comparing any GINA step 3&4 medication options. Further quality was assessed according the Cochrane Collaboration's tool and data-extracted included papers and built a network of the trials. Attempt at ranking treatments with formal statistical methods employing direct and indirect (e.g. through placebo) connections between all treatments.


RESULTS
8,175 references were screened; 23 randomized trials (RCT), comparing head-to-head (n=17) or against placebo (n=10), met the inclusion criteria. Except for theophylline as add-on therapy in step 4, a closed network allowed all comparisons to be made, either directly or indirectly. Huge variation in, and incomplete reporting of, outcome measurements across RCTs precluded assessment of relative efficacies.


CONCLUSIONS
Evidence-based ranking of effectiveness of drug treatments in GINA steps 3&4 is not possible yet. Existing initiatives for harmonization of outcome measurements in asthma trials need urgent implementation.
Division of Clinical Methods & Public Health, Department of General Practice, Academic Medical Center-University of Amsterdam, P,O, Box 22700, Amsterdam, 1100 DD, The Netherlands. l.b.vandermark@amc.uva.nl
Lonneke B
LB
van der Mark
P H Edo
PH
Lyklema
Ronald B
RB
Geskus
Jacob
J
Mohrs
Patrick J E
PJ
Bindels
Wim M C
WM
van Aalderen
Gerben
G
Ter Riet
D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005541:Forced Expiratory Volume; D006801:Humans; D017063:Outcome Assessment, Health Care; D016896:Treatment Outcome
D018927:Anti-Asthmatic Agents