Montelucast PDF
Montelucast PDF
Montelucast PDF
ABSTRACT were searched using key words asthma, MON, and ICS. Stud-
Introduction: Inhaled corticosteroids (ICS) are a first-line ies that met inclusion criteria were appraised for quality.
treatment for mild persistent asthma, but montelukast Results: Of 214 identified studies, eight met inclusion criteria
(MON) monotherapy also has been beneficial. The aim of and seven were deemed high quality. Study sample sizes
this review is to evaluate current evidence comparing MON ranged from 62 to 994, 88% were multi-site, and the average
versus ICS monotherapy in pediatric patients. length of follow-up was 8.2 months. Asthma symptoms im-
Method: A systematic review was conducted of randomized proved with both therapies. Four studies reported superior-
controlled trials evaluating treatment of mild to moderate ity of ICS compared with MON; the remaining studies
persistent asthma in which MON was compared with ICS showed no differences between therapies.
monotherapy in children aged 2 to 18 years. PubMed, the Cu- Discussion: These results are consistent with the National
mulative Index to Nursing and Allied Health Literature, and Asthma Education and Prevention Program (2007) recom-
the Institute of Scientific Information’s Web of Knowledge mendation that ICS therapy should be first-line treatment in
children with mild to moderate persistent asthma. J Pediatr
Health Care. (2014) 28, 51-62.
Kristen Massingham, Pediatric Nurse Practitioner, Essex
Pediatrics, Doctor of Nursing Practice Program, Columbia
University School of Nursing, New York, NY. KEY WORDS
Shelley Fox, Family Nurse Practitioner, Khasak Dermatology, Asthma, inhaled corticosteroids, montelukast
Doctor of Nursing Practice Program, Columbia University School
of Nursing, New York, NY. Asthma affects approximately 7 million children
Arlene Smaldone, Associate Professor of Clinical Nursing, in the United States, accounting for 9.4% of the
Columbia University School of Nursing, New York, NY. pediatric population (Centers for Disease Control and
Conflicts of interest: None to report.
Prevention, 2010). Asthma prevalence in children has
increased considerably in recent years and currently is
Correspondence: Kristen Massingham, MS, CPNP, Columbia
at the highest level reported in the United States
University School of Nursing, 630 West 168th St, New York, NY
10032; e-mail: [email protected]. (Akinbami, Moorman, & Liu, 2011). Asthma is associ-
ated with a high risk of morbidity. In children with
0891-5245/$36.00
mild persistent asthma, 52% are at risk for adverse out-
Copyright Q 2014 by the National Association of Pediatric comes, including hospitalization or emergency depart-
Nurse Practitioners. Published by Elsevier Inc. All rights
ment visits (Akinbami et al., 2011). Further, asthma
reserved.
limits daily function. Approximately 60% of children
Published online January 10, 2013. with asthma miss at least one day of school each year.
http://dx.doi.org/10.1016/j.pedhc.2012.11.005 In 2008, more than 10 million school days were missed
Identification
database searching (n=214)
Additional studies identified
from
through review of reference list
PubMed (n=105)
of included articles (n=22)
CINAHL(n= 0)
ISI Web of Knowledge (n=109)
to 994 participants, with most studies (n = 6) having ment in asthma symptoms from baseline regardless of
a sample greater than 100 participants. Most studies treatment assignment. Pulmonary function was an out-
(n = 7) were multi-site trials, with the number of study come of interest in seven studies, with results favoring
sites ranging from 3 to 104. Length of follow-up ICS over MON. These studies reported significant
ranged from 2 months to 2 years with an average of changes in peak expiratory flow rate (Maspero et al.,
8.2 months; five trials were conducted over a period 2008), forced expiratory volume in 1 second (FEV1;
of 3 months or less (Kooi et al., 2008; Kumar et al., Garcia et al., 2005; Maspero et al., 2008; Ostrom et al.,
2007; Maspero et al., 2008; Ostrom et al., 2005; 2005; Sorkness et al., 2007; Szefler et al., 2005), and
Szefler et al., 2005). The dose of ICS and MON also asthma control days (Sorkness et al., 2007). Only one
varied across studies. study that measured an objective pulmonary function
Outcome measures varied across studies. It is of in- parameter (change in FEV1) as its primary outcome de-
terest that in all studies, subjects showed an improve- tected no differences between groups (Kumar et al.,
TABLE 1. Assessment of potential bias in included randomized controlled trials using the PEDro
scoring system
Author I II III IV V VI VII VIII IX X XI Total
Garcia et al. (2005) 1 1 1 1 1 1 1 1 1 1 1 11
Kooi et al. (2008) 1 1 1 1 1 1 1 0 1 1 1 10
Kumar et al. (2007) 1 1 1 1 1 1 1 1 0 1 1 10
Maspero et al. (2008) 1 1 1 1 1 1 1 1 1 1 1 11
Ostrom et al. (2005) 1 1 1 1 1 1 1 0 1 1 1 10
Sorkness et al. (2007) 1 1 1 1 1 1 1 1 1 1 1 11
Szefler et al. (2005) 1 1 1 1 1 1 0 1 0 1 1 9
Szefler et al. (2007) 1 1 1 1 0 0 0 0 1 1 1 7
1, criteria fulfilled, low possibility of bias; 0, criteria not fulfilled, high possibility of bias.
Assessment criteria: I, Eligibility criteria specified; II, random allocation; III, allocation concealed; IV, groups similar at baseline; V, subject
blinding; VI, therapist blinding; VII, assessor blinding; VIII, less than 15% dropout rate; IX, intention-to-treat analysis; X, measurement of dif-
ference between groups in outcomes; XI, size of treatment effect and measures of variability (i.e., confidence intervals, standard errors, stan-
dard deviations, interquartile ranges, and minimum-maximum range).
ICS, none
Continued on page 56
55
56
Volume 28 Number 1
TABLE 2. Continued.
Study Multisite (yes/no) Sample size Intervention groups Study duration Study findings
Maspero et al. (2008) Yes N = 548 MON, 5 mg daily + placebo inhaler BID, versus 3 months Change in evening PEFR:
Age 6-14 years SFC, 50/100 mg inhaler BID + placebo tablet daily MON, 28.0 L/min
SFC, 46.2 L/min
FEV1 improvement:
MON, 22.08%
ICS, 33.83%
RFDs:
MON, 15 days
ICS, 24 days
(p < .001)
Treatment adherence:
MON, 84%
ICS, 87%
Ostrom et al. (2005) Yes N = 342 MON, 5 mg once daily + placebo inhaler, versus 3 months Change in FEV1:
Age 6-12 years ICS, diskus 50 mcg BID + placebo oral tablet MON, 4.60%
ICS, 10.62%
RFDs:
MON, 35.0%
ICS, 45.1%
(p = .002)
Oral corticosteroid use:
MON, 4%
ICS, 3%
Treatment adherence:
MON, 97.8%
ICS, 92.8%
Sorkness et al. (2007) Yes N = 285 MON, 5 mg in the evening + placebo diskus BID, versus 11 months Change in asthma
ICS inhaler, 100 mg BID + placebo oral tablet
Journal of Pediatric Health Care
Szefler et al. (2005) Yes N = 144 MON daily (5-10 mg) + placebo inhaler versus 2 months FEV1, % predicted:
Age 6-17 years ICS, 100 mg one puff BID + placebo oral tablet MON, .20%
Crossover design ICS, 0.32%
(p = .05)
Oral corticosteroid use:
MON, 10 children
ICS, 2 children
Treatment adherence:
MON, 97% period 1
92% period 2
ICS, 94% period 1
89% period 2
Szefler et al. (2007) Yes N = 395 MON, 4-5 mg versus 12 months Probability of having
Age 2-8 years ICS, inhaled suspension 0.5 mg daily an event:
MON, 9.6%
ICS, 6.6%
p = NS
FEV1:
MON, 0.05 L
ICS, 0.09 L
p = NS
RFDs:
MON, 37.24%
ICS, 38.74%
p = NS
Oral corticosteroid use:
MON, 32%
ICS, 25.5%
Treatment adherence:
MON, 82.8%
ICS, 82.9%
BID, Twice a day; EFD, episode-free day; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; MON, montelukast; RFD, rescue-free day; PEFR, peak expiratory flow rate; NS, no
significant difference; SFC, salmeterol/fluticasone propionate.
January/February 2014
57
2007). Six studies measured rescue-free days, with the trials, only one study (Garcia et al., 2005) reported the
majority reporting superiority of ICS over MON change in eosinophil level in the MON and ICS groups
(Garcia et al., 2005; Maspero et al., 2008; Ostrom before and after intervention ( 0.08 103 vs. 0.06
et al., 2005; Sorkness et al., 2007). In general, studies 103, p = .411). Three studies measured the child’s linear
that found no differences between treatment groups growth over the duration of the study. One study found
measured more subjective patient outcomes: change that children in the MON group demonstrated greater
in daily symptom score (Kooi et al., 2008) and change annual height increase compared with the ICS group
in the probability of asthma exacerbation (Szefler (6.18 vs. 5.81 cm, p = .018; Garcia et al., 2005). The re-
et al., 2007). maining two studies found no differences between
Clinical adverse events were reported in all studies groups (Sorkness et al., 2007; Szefler et al., 2007).
and favored ICS versus MON. Asthma exacerbation Several areas of bias were noted across studies. Two
was the most frequently reported event and was re- studies had sample sizes of less than 100 subjects and
ported in all eight studies. Across studies, 182 of 1,345 may have lacked statistical power to detect treatment
children (13.5%) assigned to MON and 128 of 1,468 chil- differences; thus the results may be subject to type II er-
dren (8.7%) assigned to ICS experienced an asthma ex- ror (Kooi et al., 2008; Kumar et al., 2007). Furthermore,
acerbation; the risk of asthma exacerbation was 1.6 five of the studies were conducted for a 3-month dura-
times higher (relative risk [RR] 1.56, 95% confidence in- tion or less (Kooi et al., 2008; Maspero et al., 2008;
terval [CI] 1.3-1.9) for children assigned to MON com- Ostrom et al., 2005; Szefler et al., 2005), a period that
pared with ICS. Five studies reported the need for oral may have been too short to fully evaluate treatment re-
corticosteroid use (Kooi et al., 2008; Kumar et al., sponse and maintenance of asthma control.
2007; Ostrom et al., 2005; Szefler et al., 2005; Szefler
et al., 2007). Across studies, 81 of 488 children (16.6%) DISCUSSION
assigned to MON and 58 of 498 children assigned to Summary of Evidence
ICS (11.6%) required oral corticosteroids, with the risk Eight RCTs comparing the effects of ICS and MON in the
of oral corticosteroid use 1.4 times higher (RR 1.43, treatment of pediatric patients with mild to moderate
95% CI 1.04-1.9) for children assigned to MON versus persistent asthma were included in this systematic re-
ICS. Other less frequently reported events were head- view. All studies demonstrated that, regardless of treat-
ache (Maspero et al., 2008; Ostrom et al., 2005), upper ment assignment, asthma symptoms improved from
respiratory infection (Kooi et al., 2008; Ostrom et al., baseline. This im-
2008), and skin rash (Kooi et al., 2008; Kumar et al., provement may be .although four
2007). related to several fac-
Six studies measured treatment adherence using self- tors, including re- studies favored ICS
report (n = 3), pill counts (n = 4), diskus counts (n = 4), sponse to the assigned and four studies
and Electronic Drug Exposure Monitor (n = 2) methods. treatment medication found no
Three studies used more than one method to measure or the Hawthorne ef-
treatment adherence, such as measuring capsule counts fect, where subjects differences
and diskus dose indicator in addition to either diary may change their be- between groups,
cards or an electronic measure (Ostrom et al., 2005; havior because they no study found
Sorkness et al., 2007; Szefler et al., 2005). On average, are aware that they are
self-reported adherence was high ($ 80%) across stud- in a clinical trial. Im- MON monotherapy
ies. Study findings were inconsistent across studies. portantly, although superior to
Two studies reported higher adherence in the MON four studies favored monotherapy with
group (Ostrom et al., 2005; Szefler et al., 2005), two re- ICS and four studies
ported higher adherence in the ICS group (Maspero found no differences ICS.
et al., 2008; Sorkness et al., 2007), and two found no dif- between groups, no
ferences in adherence between the MON and ICS study found MON monotherapy superior to monother-
groups (Garcia et al., 2005; Szefler et al., 2007). apy with ICS. In addition, the two studies that reported
Less frequently measured outcomes of interest were no differences between groups had small samples and
school and parental work attendance, eosinophil may have lacked statistical power to detect differences
count, and linear growth. One study examined missed between treatments, leading to type II error.
school days (children) and missed work days (parents) Most studies restricted their inclusion criteria to chil-
and found no differences between children in the ICS dren with mild persistent asthma. Only three studies in-
group compared with the MON group (2.1% vs. 1.9%) cluded children with moderate persistent asthma
during the 12-month trial (Garcia et al., 2005). Three (Ostrom et al., 2005; Sorkness et al., 2007; Szefler
studies measured serum eosinophil levels, and none et al., 2005). Therefore the ability to generalize the study
found differences between groups (Garcia et al., findings must be considered cautiously in treatment of
2005; Kooi et al., 2008; Szefler et al., 2005). Of these patients with moderate asthma. In addition, the ability