Randomized, placebo-controlled study of cetirizine and

loratadine in children with seasonal allergic rhinitis

Anjuli S. Nayak, M.D.,† William E. Berger, M.D.,1 Craig F. LaForce, M.D.,2
Eduardo R. Urdaneta, M.D.,3 Mitesh K. Patel, Pharm.D.,3 Kathleen B. Franklin, R.N.,4 and

Y
Mei-Miau Wu, Dr.P.H.5

ABSTRACT
Background: Pharmacologic treatment is a mainstay of allergy therapy and many caregivers use over-the-counter
antihistamines for the treatment of seasonal allergic rhinitis (SAR) symptoms in children.
Objective: To assess the efficacy and safety of cetirizine 10 mg syrup versus loratadine 10 mg syrup versus placebo syrup

P
O
in a randomized double-blind study of children, ages 6 –11 years, with SAR.
Methods: This randomized, double-blind, parallel-group, placebo-controlled study was conducted at 71 U.S. centers during
the spring tree and grass pollen season. After a 1-week placebo run-in period, qualified subjects were randomized to once-daily
cetirizine 10 mg (n ⫽ 231), loratadine 10 mg (n ⫽ 221), and placebo (n ⫽ 231) for 2 weeks. The primary efficacy end point

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was change from baseline in the subject’s mean reflective total symptom severity complex (TSSC) score over 14 days.
Results: Children treated with cetirizine experienced significantly greater TSSC score reductions versus children treated
with placebo over 14 days (least square mean change, ⫺2.1 versus ⫺1.6; p ⫽ 0.006). The differences in TSSC score
improvement over 14 days between the cetirizine versus loratadine groups (⫺2.1 versus ⫺1.8; p ⫽ 0.124) and between the

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loratadine versus placebo groups (⫺1.8 versus ⫺1.6; p ⫽ 0.230) were not statistically significant. Predominant adverse events
in the cetirizine, loratadine, and placebo groups were headache (3.5, 3.6, and 3.1%, respectively) and pharyngitis (3.5, 2.7, and
3.5%, respectively). Somnolence was reported in three subjects (1.3%) treated with cetirizine and in none of the other subjects.
Conclusion: Cetirizine 10 mg was statistically significantly more efficacious than placebo in the treatment of SAR

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symptoms in children ages 6 –11 years. Symptom improvement was not significantly different between the loratadine 10 mg
and placebo groups.
(Allergy Asthma Proc 38:222–230, 2017; doi: 10.2500/aap.2017.38.4050)

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llergic rhinitis, with its associated rhinorrhea,
sneezing, congestion, and/or nasoocular pruri-
tus, is one of the most common chronic diseases that
affect children.1 A global survey of ⬃1.2 million chil-
of allergic rhinitis symptoms commonly occurs after 3
years of age; however, food and airborne allergen sen-
sitizations may be discernible at an earlier age.3,4 There
is evidence to indicate that, in some children, allergic

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dren in 98 countries determined that the prevalence of
rhinoconjunctivitis in children ages 6 –7 years and
13–14 years was 8.5 and 14.6%, respectively.2 The onset
rhinitis represents a stage in the progression of the
atopic march.3,5,6 In childhood, allergic rhinitis may
present as recurrent sore throats and upper respiratory
tract infections. These symptoms may mistakenly be

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From the 1Allergy and Asthma Associates of Southern California, Mission Viejo,
California, 2Medical Director, North Carolina Clinical Research, Raleigh, North
Carolina, 3Medical Affairs, Johnson & Johnson Consumer Inc., McNeil Consumer
Healthcare Division, Fort Washington, Pennsylvania, 4Franklin Consultants, Phoe-
nixville, Pennsylvania, and 5Quantitative Sciences, Johnson & Johnson Consumer
Inc., Morris Plains, New Jersey
†Deceased
The original clinical study was supported by Pfizer, Inc. Publication of the study
results was supported by Johnson Consumer Inc., McNeil Consumer Healthcare
Division
E. Urdaneta was an employee of Johnson & Johnson Consumer Inc., McNeil Consumer
Healthcare Division, while authoring this publication. M. Patel is an employee of
Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division. M. Wu is
an employee of Johnson & Johnson Consumer Inc. K. Franklin is a consultant to
McNeil Consumer Healthcare. The remaining authors have no conflicts of interest
pertaining to this article
Address correspondence to Kathleen B. Franklin, R.N., Franklin Consultants, 180
East Beacon Drive, Phoenixville, PA 19460
E-mail address: kfrankl1@its.jnj.com
Copyright © 2017, OceanSide Publications, Inc., U.S.A.
attributed to colds or other disorders, and allergic rhi-
nitis may remain untreated.7,8 In cases in which the
young child is unable to articulate and describe his or
her symptoms, allergic rhinitis may remain undiag-
nosed.9
Treatment of allergic rhinitis in children is primarily
focused on allergen avoidance and pharmacologic
therapy. Cetirizine, a H1 receptor antagonist that is
available over-the-counter (OTC), has been shown to
be well tolerated and effective in children with sea-
sonal allergic rhinitis (SAR)10 –14 and perennial allergic
rhinitis.15–17 In addition to its antihistaminic proper-
ties, cetirizine is considered to have broad anti-inflam-
matory effects, including the inhibition of leukocyte
influx,18 the reduction of intercellular adhesion mole-
cule 1 expression,19 and the augmentation of interleu-
kin 10 and interferon gamma production.20 Survey

222 May–June 2017, Vol. 38, No. 3

data indicate a high prevalence rate of OTC medicine
use in children ⬍18 years of age. In a study of 8145
children in the United States, 70% of respondents
stated that they used OTC medications to treat their
child’s recent illness.21 Therefore, the objective of this
study was to add to the current knowledge regarding
the efficacy and safety of cetirizine treatment in chil-
dren with SAR symptoms.
METHODS
Subject Characteristics
The study participants were 6 –11 years of age with a
SAR diagnosis to grass or tree pollen of such severity
that it required pharmacologic therapy each year for
the past 2 consecutive years. SAR was confirmed by a
recognized skin test (prick, intradermal, or Multitest,
Lincoln Diagnostics, Inc., Decatur, IL) within the pre-
vious 15 months (prick and/or puncture wheal of ⱖ3
mm larger than the negative control; intradermal [up
to a concentration of 1:1000 w/v or 1000 protein nitro-
gen units wheal of ⱖ5 mm larger than the negative
control]). Girls who reached menarche, either before or
during the study, had to agree to use acceptable meth-
ods of birth control if they became sexually active.
Clinically significant nasal anatomic deformities, a his-
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tory of chronic sinusitis, or a major systemic disease
were criteria for exclusion. Individuals who were re-
ceiving intranasal, ocular, or systemic corticosteroids;
oral leukotriene modifiers; immunotherapy; or oral or
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topical antihistamines were not eligible for the study.
Study Design
The randomized, double-blind, parallel-group, pla-
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cebo-controlled study consisted of a 7-day placebo
run-in period and a 2-week treatment period, and was
conducted at 77 centers in the midwestern, western,
and southern United States during the spring season
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from April 29 to July 25, 2001. The study complied with
Good Clinical Practices and was conducted in full com-
pliance with the World Medical Assembly Declaration
of Helsinki (ClinicalTrials ID NCT02932774). The Co-
pernicus Central Institutional Review Board (IRB) ap-
proved the protocol, protocol amendments, and subject
informed consent for most investigative sites. The re-
maining sites obtained approval from local IRBs, in-
cluding Creighton University, University of Chicago,
St. Vincent Hospital, Vanderbilt, and University of
Iowa. Written informed consent and subject assent
were obtained before study entry. The subjects were
evaluated at the clinic at screening (visit 1), at the
baseline visit performed after the 1-week placebo
run-in period (visit 2), and at weekly intervals dur-
ing the 14-day double-blind treatment period (visits
3 and 4).
Allergy and Asthma Proceedings
At screening (visit 1), the investigator performed a
physical examination, collected vital signs, and re-
viewed the child’s medical history. The subject or the
parent or guardian (guardian) was given placebo
syrup and diaries in which the subject’s self-assessed
symptom severity scores were recorded daily before
10:00 AM and before taking the study medication.
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Symptom severity was based on the subject’s assess-
ment of symptoms in an instantaneous (at that moment
of evaluation) and a reflective (over the past 24 hours
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since the last dose) manner. Instantaneous and reflec-
tive severity scores for sneezing, runny nose, itchy
eyes, and watery eyes were recorded on a four-point
scale (0 [none, complete absence of symptoms] to 3
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[severe, symptoms present day and night, impact on
daily activities, as well as on ability to sleep]). The total
symptom severity complex (TSSC) score was the sum
of the four individual symptom scores. Nasal conges-
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tion was graded separately in the daily diaries in the
same instantaneous and reflective manner and on the
same four-point scale.
Subject diaries were collected and reviewed at every
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visit; concomitant medications and adverse events
(AEs) were recorded. At baseline (visit 2), subjects
qualified for randomization if, on ⱖ4 days of the pla-
cebo run-in period, they had scores of moderate or
more intensity (ⱖ2 on scale of 0 –3) for at least two of
the four symptoms that comprise the TSSC score. In
addition, the subjects had to have a TSSC score of ⱖ5
on any 4 days of the placebo run-in period. Qualified
subjects were randomly assigned to receive cetirizine
syrup 10 mg (1 mg/mL), loratadine syrup 10 mg (1
mg/mL), or placebo syrup in a double-blind fashion
(1:1:1 ratio) for 2 weeks. The subjects continued to
record daily symptom assessments in their diaries dur-
ing the treatment period.
At visits 2, 3, and 4, the investigators evaluated the
subjects’ symptoms since the last visit by using a scale
from 0 (none, complete absence of symptoms) to 3
(severe, symptoms present day and night, impact on
daily activities, as well as on ability to sleep). At visits
2, 3, and 4, the guardians assessed the subject’s symp-
toms since the last visit by answering the following
questions: (1) how often did your child sneeze, (2) how
often did your child have a runny nose, (3) how often
did your child have itchy eyes, (4) how often did your
child have watery eyes, and (5) how often did your
child have a stuffy nose? The guardian used a four-
point scale to answer the questions, from 0 (not at all)
to 3 (very often). The guardians also evaluated the
social and emotional impact of caring for a child with
SAR by answering the following questions on a Paren-
tal Burden Questionnaire at visits 2, 3, and 4, or at early
termination: Over the past week, how much did your
child’s allergies (1) interfere with your normal social
activities with family, friends, or groups; (2) interfere
223
with your ability to conduct routine daily activities
(other than your job and/or volunteer work); (3) cause
you to worry about his or her health; (4) interfere with
your ability to work; and (5) interfere with your ability
to be productive at work? The impact of caring for a
child with SAR was recorded by using a scale from 1
(not at all) to 5 (extremely).
At visit 4 or at early termination, the subject, with or
without his or her guardian, provided a global treat-
ment evaluation by answering the following question:
Overall, how would you evaluate your response to the
treatment you received for your allergy? The subject
assessed his or her overall treatment responses by us-
ing a scale from 1 (a lot better) to 5 (a lot worse). At
visit 4 or at early termination, the guardian completed
an appraisal of personal satisfaction with the treatment
by answering the following question: overall, how sat-
isfied are you with the medication that your child
received during the study? The guardian used a five-
point scale to rate overall personal satisfaction, from 1
(very satisfied) to 5 (very dissatisfied). At visit 4 or
early termination, the investigator used a seven-point
scale to assess the treatment’s effect, from 1 (major
improvement; all signs and/or symptoms improved)
to 7 (severe worsening; all signs and/or symptoms
worsened). The investigator recorded a global assess-
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ment at visit 4 or early termination to assess the treat-
ment effect: 1 (major improvement; all signs and/or
symptoms improved) to 7 (severe worsening; all signs
and/or symptoms worsened). Final assessments, in-
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cluding a physical examination, were performed at the
last visit or at early study termination.
Efficacy End Points
The primary efficacy end point was the change from
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baseline in the subject’s mean 24-hour reflective TSSC
score over 14 days. Changes from baseline in the sub-
ject’s mean reflective TSSC score over week 1 and week
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2 of treatment were secondary end points. Additional
secondary end points included the following: the sub-
ject’s mean reflective TSSC score plus stuffy nose score,
subject’s instantaneous TSSC score, subject’s instanta-
neous TSSC score plus stuffy nose score, subject’s indi-
vidual symptom scores (reflective and instantaneous),
guardian’s evaluation of the subject’s symptoms, investi-
gator’s evaluation of subject’s symptoms, and guardian’s
response on the Parental Burden Questionnaire. The
guardian’s overall personal satisfaction assessment, sub-
ject global evaluation of treatment, and investigator
global evaluation of treatment were also secondary effi-
cacy end points.
Safety
Safety was evaluated by summarizing observed or
subject-reported AEs, vital sign measurements, physi-
224
cal examination findings, and concomitant medication
use. AEs were categorized as treatment-related if, in
the investigator’s judgment, they were most likely
caused by the study drug or if the causality was un-
known. Clinical laboratory evaluations were not re-
quired.
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Statistical Methods
Treatment group comparisons were made on the
change from baseline values in efficacy end points that
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involved rhinoconjunctivitis symptoms and Parental
Burden Questionnaire scores treated as a continuous
variable by using a two-way analysis of covariance
model with terms for treatment and investigator site,
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with the baseline value as a covariate. Least square
means based on this main effect model were used to
estimate treatment effect. Pairwise comparisons were
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made only if the overall treatment effect was signifi-
cant (Fisher protected least significant difference).
Treatment group differences for all categorical efficacy
end points (i.e., Parental Burden Questionnaire in its
original categorical scale, global evaluations, and par-
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ent or guardian overall satisfaction assessment) were
analyzed by using Cochran–Mantel–Haenszel row
mean test scores stratified by investigator site. All sta-
tistical tests related to treatment effect were two-sided,
and statistical significance was declared at the 0.05
probability level.
By using a two-sided test, a sample size of ⬃330
subjects per treatment group would assure 81% power
to detect a difference of 1.0 point in the mean change
from baseline in the primary efficacy variable of TSSC
scores between the cetirizine and loratadine treatment
groups at the 0.05 significance level with assuming a
pooled standard deviation of 4.5. The primary efficacy
analysis was based on intention-to-treat subjects, de-
fined as subjects who were randomized, received at
least one dose of study medication and had at least one
efficacy end point at baseline and at any subsequent
visit. Safety was evaluated for all randomized subjects
who received at least one dose of study medication.
RESULTS
Patient Characteristics
Of 683 subjects randomized to treatment, safety was
evaluated for 677 subjects who received at least one
dose of cetirizine (n ⫽ 228), loratadine (n ⫽ 220), or
placebo (n ⫽ 229). These 677 subjects in the safety
population were comparable at baseline with respect to
sex, race, and age (p ⬎ 0.05) (Table 1). Efficacy was
evaluated in 677 intention-to-treat subjects in the ceti-
rizine (n ⫽ 210), loratadine (n ⫽ 201), and placebo (n ⫽
214) groups; 52 subjects discontinued the study: 18 in
the cetirizine group (7.9%), 19 in the loratadine group
(8.6%), and 15 in the placebo group (6.6%). One subject
May–June 2017, Vol. 38, No. 3
Table 1 Demographic and baseline characteristics of 677 in safety population*
Characteristic Cetirizine Loratadine Placebo
(n ⴝ 228) (n ⴝ 220) (n ⴝ 229)
Age, mean ⫾ SD, y 8.6 ⫾ 1.7 8.9 ⫾ 1.6 8.9 ⫾ 1.6
Sex, no. (%)

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Boys 131 (57.5) 125 (56.8) 123 (53.7)
Girls 97 (42.5) 95 (42.2) 106 (46.3)
Race, no. (%)
White 173 (75.8) 170 (77.2) 167 (72.9)

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Black 31 (13.5) 26 (11.8) 39 (17.0)
Other 24 (10.5) 24 (10.9) 23 (10.0)
Weight, mean ⫾ SD, kg
Boys 34.0 ⫾ 9.9 35.5 ⫾ 11.0 34.5 ⫾ 10.3

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Girls 33.2 ⫾ 11.7 36.3 ⫾ 11.9 35.2 ⫾ 10.4
Duration since first PAR diagnosis, mean 5.4 (1.1–11.5) 5.6 (1.1–12.3) 5.6 (0.6–11.7)
(range), y

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Drugs used to treat allergic disorders required 159 (69.7) 155 (70.5) 155 (67.7)
in 3 mo before study, no. (%)
Baseline TSSC score, mean ⫾ SE# 7.5 ⫾ 0.1 7.5 ⫾ 0.1 7.7 ⫾ 0.1
SD ⫽ Standard deviation; PAR ⫽ perennial allergic rhinitis; TSSC ⫽ total symptom severity complex; SE ⫽ standard error.

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*The p values for the three treatment groups were 0.094, 0.754, and 0.302, for age, sex, and race, respectively.
#The baseline TSSC score is defined as the mean of the last three non-missing scores at and before visit 2.

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Table 2 Discontinuations from the study
Cetirizine, no. (%) Loratadine, no. (%) Placebo, no. (%)
Related to the study drug

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Adverse event 1 (0.4) 1 (0.5) 0
Lack of efficacy 0 2 (0.9) 2 (0.9)
Not related to the study drug
Adverse event 5 (2.2) 9 (4.1) 7 (3.1)
Other 10 (4.4) 5 (2.3) 5 (2.2)

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Lack of efficacy 2 (0.9) 2 (0.9) 1 (0.4)
Total 18 (7.9) 19 (8.6) 15 (6.6)

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taking cetirizine, three subjects taking loratadine, and
two subjects taking placebo discontinued the study
due to drug-related events. Five subjects in the ceti-
rizine group, nine subjects in the loratadine group,
and seven subjects in the placebo group discontin-
ued the study due to AEs not related to the study
drug (Table 2).
Efficacy Results
Primary Efficacy End Point. At baseline, there were no
significant differences in the reflective TSSC scores
among the cetirizine, loratadine, and placebo groups:
7.5, 7.6, 7.7, respectively; p ⫽ 0.590. Over the 14-day
treatment period, the subjects treated with cetirizine
experienced a significantly greater improvement in the
reflective TSSC score compared with subjects taking
placebo: ⫺2.1 and ⫺1.6, respectively; p ⫽ 0.006 (Fig. 1).
The difference in the reflective TSSC score improve-
ment between the cetirizine (⫺2.1) and loratadine
(⫺1.8) groups did not reach statistical significance (p ⫽
0.124). The loratadine group (⫺1.8) and placebo (⫺1.6)
group scores did not show a statistical difference either
(p ⫽ 0.230) (Table 3 and Fig. 1).
Secondary Efficacy End Points. Baseline values were
not statistically different among the treatment groups
for the secondary efficacy end points, with the excep-
tion of the score for one individual item on the Parental
Burden Questionnaire, “How much did your child’s
allergies interfere with your ability to be productive at
work?” Over week 1, children treated with cetirizine
experienced significantly greater improvements in the
reflective TSSC score compared with children treated
with placebo (⫺1.6 and ⫺1.1, respectively; p ⫽ 0.010).

Allergy and Asthma Proceedings 225

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Figure 1. Mean change from baseline in reflective total symptom severity complex (TSSC) score.

period*

Baseline, mean ⫾ SE
14-Day period, mean ⫾ SE
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Table 3 Primary end point: Change from baseline in the mean reflective TSSC scores during a 14-day

Cetirizine
(n ⴝ 228)
7.5 ⫾ 0.1
5.5 ⫾ 0.2
Loratadine
(n ⴝ 219)
7.6 ⫾ 0.1
5.8 ⫾ 0.2
Placebo
(n ⴝ 229)
7.7 ⫾ 0.1
6.1 ⫾ 0.2
p Value

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Change from baseline, LS mean ⫾ SE ⫺2.1 ⫾ 0.2 ⫺1.8 ⫾ 0.2 ⫺1.6 ⫾ 0.2
Overall treatment effect 0.022
Cetirizine vs placebo 0.006
Cetirizine vs loratadine 0.124

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Loratadine vs placebo 0.230
TSSC ⫽ Total symptom severity complex; SE ⫽ standard error; LS ⫽ least square.
*The baseline TSSC score is defined as the mean of the last three non-missing scores at and before visit 2.

The week 1 differences between the cetirizine and lo-
ratadine groups (⫺1.6 and ⫺1.2, respectively) and the
loratadine and placebo groups (⫺1.2 and ⫺1.1, respec-
tively) were not statistically significant (Table 4 and
Fig. 1). Over week 2, children who were treated with
cetirizine experienced significant improvement in the
reflective TSSC score compared with the placebo group
(⫺2.8 and ⫺2.3, respectively; p ⫽ 0.027). The differ-
ences over week 2 between the cetirizine and lorata-
dine groups (⫺2.8 and ⫺2.5, respectively) and lorata-
dine and placebo groups (⫺2.5 and ⫺2.3, respectively)
were not statistically significant (Table 4 and Fig. 1).
Over 2 weeks, improvement in the reflective TSSC
score plus the stuffy nose score was significantly
greater for subjects treated with cetirizine compared
with subjects treated with placebo (p ⫽ 0.011). Over the
same period, the differences between cetirizine and
loratadine and between loratadine and placebo were
not statistically significant. For the reflective individual
symptoms scores, improvements in sneezing scores
over 14 days were significantly greater in the cetirizine
group compared with placebo (p ⫽ 0.007). For reflec-
tive runny nose, itchy eyes, watery eyes, and stuffy
nose scores, the differences were not statistically sig-

226 May–June 2017, Vol. 38, No. 3

Table 4 Secondary end point: Change from baseline in the mean reflective TSSC scores during the first and
second weeks of treatment
Cetirizine Loratadine Placebo p Value
Week 1
No. patients 228 218 229
Baseline, mean ⫾ SE 7.5 ⫾ 0.1 7.5 ⫾ 0.1 7.7 ⫾ 0.1

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Week 1, mean ⫾ SE 6.0 ⫾ 0.2 6.3 ⫾ 0.2 6.5 ⫾ 0.2
Change from baseline, LS mean ⫾ SE ⫺1.6 ⫾ 0.2 ⫺1.2 ⫾ 0.2 ⫺1.1 ⫾ 0.2
Overall treatment effect 0.030

P
Cetirizine versus placebo 0.010
Cetirizine versus loratadine 0.068
Loratadine versus placebo 0.471
Week 2

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No. patients 213 207 217
Baseline, mean ⫾ SE 7.6 ⫾ 0.1 7.5 ⫾ 0.1 7.7 ⫾ 0.1
Week 2, mean ⫾ SE 5.0 ⫾ 0.2 5.2 ⫾ 0.2 5.4 ⫾ 0.2
Change from baseline, LS mean ⫾ SE ⫺2.8 ⫾ 0.2 ⫺2.5 ⫾ 0.2 ⫺2.3 ⫾ 0.2
Overall treatment effect
Cetirizine vs placebo
Cetirizine vs loratadine
Loratadine vs placebo
C 0.086
n/a
n/a
n/a

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TSSC ⫽ Total symptom severity complex; SE ⫽ standard error; LS ⫽ least square; n/a ⫽ not applicable.
Pairwise comparisons were not performed because the overall treatment effect was not significant (p ⬎ 0.05).

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nificant among the groups (Fig. 2). The reduction in
mean instantaneous TSSC scores over 14 days was
significantly greater for the cetirizine group compared

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with placebo (p ⫽ 0.014). The differences between ce-
tirizine and loratadine, and between loratadine and
placebo were not statistically significant. Over 2 weeks,
improvement in the instantaneous TSSC plus stuffy
nose scores were not significantly different among the
placebo and p ⫽ 0.016 versus loratadine, respec-
tively). The differences for the remaining Parental
Burden Questionnaire individual question scores
were not statistically different among the groups.
For the global evaluation of treatment, the subjects
rated their response to treatment as “a lot better” in
22.8% of subjects treated with cetirizine, 21.9% of sub-
jects treated with loratadine, and 17.5% of subjects on

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groups. For the 14-day instantaneous itchy eye score,
cetirizine and loratadine showed a significant reduc-
tion versus placebo (p ⫽ 0.019 and p ⫽ 0.042 versus
placebo, respectively). The difference between the two
placebo. The differences in subject-assessed global
evaluation scores for the individual response catego-
ries, from “a lot better” to “a lot worse,” were not

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active treatment groups was not statistically different.
For the remaining four instantaneous individual symp-
tom scores, the improvements from baseline were not
significant among the groups.
The cetirizine and loratadine groups had statistically
greater reductions over 2 weeks in the investigator-
assessed TSSC scores compared with placebo (p ⬍
0.001 and p ⫽ 0.021 compared with placebo, respec-
tively) and the guardian-assessed TSSC scores (p ⫽
0.018 and p ⫽ 0.038 compared with placebo, respec-
tively). There were no significant differences between
the cetirizine and loratadine groups in these end point
results. For the individual question “how much did
your child’s allergies interfere with your ability to be
productive at work” over 2 weeks, improvements in
the cetirizine group were statistically superior to the
placebo and loratadine groups (p ⫽ 0.028 versus
significantly different among the treatment groups. In-
vestigators assessed global treatment responses as a
“major improvement” in 12.7% of subjects treated with
cetirizine, 8.2% of subjects treated with loratadine, and
10.0% of subjects treated with placebo. The differences
in investigator-assessed global evaluation scores for
the individual response categories from “major im-
provement” to “severe worsening” were not signifi-
cantly different among the treatment groups. For the
guardian-assessed overall personal satisfaction assess-
ment, 16.7% of the guardians in the cetirizine group,
14.2% of the guardians in the loratadine group, and
11.4% of the guardians in the placebo group were
“very satisfied’ with the treatment. There was a signif-
icant difference among the three treatment groups for
the individual response categories from “very satis-
fied” to “very dissatisfied” (p ⫽ 0.017). The difference

Allergy and Asthma Proceedings 227


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N O
Figure 2. Mean change from baseline in the reflective individual symptom scores over the 14-day period.
in the response category ratings between the cetirizine
and loratadine groups was not significant.
Safety Evaluation
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Safety data were evaluable for 677 children. Similar
incidences of concomitant medication use were reported
in the cetirizine, loratadine, and placebo groups: 39.0,
39.5, and 39.7%, respectively. Drugs used in allergic dis-
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orders were required by 23 subjects in the cetirizine
group (10.1%), 16 subjects in the loratadine group (7.3%),
and 24 subjects in the placebo group (10.5%). Incidences
of all-causality AEs were similar in the cetirizine, lor-
atadine, and placebo treatment groups: 19.7, 21.8, and
22.7%, respectively. The predominant all-causality AEs
in the cetirizine, loratadine, and placebo groups were
headache (3.5, 3.6, and 3.1%, respectively) and pharyn-
gitis (3.5, 2.7, and 3.5%, respectively). Somnolence was
reported in three subjects only in the cetirizine group
(1.3%) (Table 5). The incidences of treatment-related
AEs were 4.8% for cetirizine, 4.5% for loratadine, and
2.6% for placebo (Table 6). All of the treatment-related
AEs were mild or moderate in severity. Vomiting was
the most frequently reported treatment-related AE,
with 0.9% of subjects treated with cetirizine, 1.8% of
subjects treated with loratadine, and 0.4% of subjects
228
P Y
C O
treated with placebo who reported the event. There
were no serious AEs in this study.
DISCUSSION
In this 14-day study of 677 children ages 6 to 11
years, cetirizine 10 mg produced significantly greater
SAR symptom relief compared with placebo as deter-
mined by the primary study end point: TSSC score
reductions from baseline over 2 weeks. The differences
in TSSC score improvement between cetirizine 10 mg
and loratadine 10 mg as well as between loratadine 10
mg and placebo were not statistically significant. Over
2 weeks, cetirizine was significantly more effective
than placebo for the following seven secondary effi-
cacy parameters: reflective TSSC score with stuffy
nose, instantaneous TSSC score, reflective sneezing
score, instantaneous itchy eye scores, investigator-as-
sessed TSSC score, guardian-assessed TSSC score, and
the item “how much did your child’s allergies interfere
with your ability to be productive at work” on the
Parental Burden Questionnaire. Compared with pla-
cebo, loratadine produced significant improvements
over 2 weeks in the following three secondary efficacy
end points: instantaneous itchy eyes scores, investiga-
tor-assessed TSSC scores, and guardian-assessed TSSC
May–June 2017, Vol. 38, No. 3
Table 5 All causality AEs with a >1% incidence, safety-analyzable set
AE Cetirizine, no. (%) Loratadine, no. (%) Placebo, no. (%)
(n ⴝ 228) (n ⴝ 220) (n ⴝ 229)
Headache 8 (3.5) 8 (3.6) 7 (3.1)
Pharyngitis 8 (3.5) 6 (2.7) 8 (3.5)

Y
Fever 4 (1.8) 2 (0.9) 2 (0.9)
Vomiting 3 (1.3) 6 (2.7) 2 (0.9)
Sinusitis 3 (1.3) 4 (1.8) 4 (1.7)
Somnolence 3 (1.3) 0 (0.0) 0 (0.0)

P
Lymphadenopathy 1 (0.4) 4 (1.8) 0 (0.0)
Asthma 1 (0.4) 1 (0.5) 3 (1.3)
Nausea 0 (0.0) 4 (1.8) 2 (0.9)
Epistaxis 0 (0.0) 3 (1.4) 2 (0.9)

O
Bronchitis 0 (0.0) 0 (0.0) 3 (1.3)
AE ⫽ Adverse event.

Table 6 Treatment-related AEs with >1% incidence, safety-analyzable set*

AE Cetirizine, no. (%)
(n ⴝ 228)
C
Loratadine, no. (%)
(n ⴝ 220)
Placebo, no. (%)
(n ⴝ 229)

T
Somnolence 3 (1.3) 0 (0.0) 0 (0.0)
Vomiting 2 (0.9) 4 (1.8) 1 (0.4)
Headache 2 (0.9) 3 (1.4) 0 (0.0)

O
Nausea 0 (0.0) 3 (1.4) 2 (0.9)
AE ⫽ Adverse event.
*AEs are deemed if, in the investigator’s judgment, the study drug was the most likely cause of the AE or if the causality was
missing.

N
scores. Cetirizine was well tolerated; incidences of all-
causality AEs, treatment-related AEs, and AEs that led
The subjects treated with cetirizine experienced a
significantly greater percentage of days when symp-

O
to discontinuation were similar among the three treat-
ment groups. Somnolence was reported in 1.3% of the
subjects in the cetirizine group.
These findings strengthened the evidence from ear-
toms were absent or mild (56.2%) than subjects treated
with placebo (29.7%) (p ⱕ 0.05). Investigator-rated DSS
also improved more with cetirizine than placebo after
1 week (p ⫽ 0.007) and 2 treatment weeks (p ⬍ 0.001).

D
lier randomized, placebo-controlled studies, which
also concluded that cetirizine 10 mg is a well-tolerated
and effective therapy for the relief of symptoms in
children with SAR.11,12 In a 2-week pediatric study,
Masi et al.11 found that cetirizine 10 mg (n ⫽ 63) was
significantly superior to placebo (n ⫽ 61) for the pri-
mary end point of days with no or mild symptoms. A
subject-reported disease severity score (DSS) was used
to evaluate the efficacy of cetirizine 5 mg administered
twice daily to children ages 6 to 12 years with seasonal
allergic rhinoconjunctivitis. The DSS was the maxi-
mum score of any of the five symptoms assessed (rhi-
norrhea, sneezing, blocked nose, or pruritus that in-
volved the nose or eyes). The primary end point of the
study was the percentage of days over the 2-week
treatment period when the DSS was ⱕ1 (absent or mild
symptoms).
In another study, cetirizine 10 mg syrup administered
once daily (n ⫽ 70) produced significantly greater
mean total symptom severity (TSS) score reductions
than placebo (n ⫽ 66) in children ages 6 to 11 years old
with SAR (p ⬍ 0.05).12 TSS was the sum of sneezing,
nasal discharge, itchy oral and/or nasal mucosa, itchy
eyes, and conjunctivitis severity scores. The subjects
rated symptoms on a four-point scale, from 0 (none) to
3 (severe). Over the entire 4-week period, reductions in
the mean TSS scores were 3.19 and 2.09 in the cetirizine
and placebo groups, respectively (p ⱕ 0.05). Cetirizine
10 mg also reduced individual symptoms more effec-
tively than placebo, with a significant difference for
ocular itching and oral and/or nasal itching (p ⬍ 0.05).
For children in the present study who were too
young to accurately verbalize and record their self-
assessment in daily diaries, the guardians evaluated

Allergy and Asthma Proceedings 229

symptom severity. The substitution of the guardian’s
symptom severity interpretation, in place of the sub-
ject’s self-report, may have introduced bias into the
study results. Analysis of the research indicated that
there may be significant differences between the level
of actual interference caused by allergic rhinitis that the
child experiences and what is perceived by the guard-
ian or health care provider.22 The same may be true for
symptom severity assessments, with guardians and
investigators rating symptom severity less severe than
would the pediatric subjects themselves.
CONCLUSION
Over a 2-week period, cetirizine 10 mg was statisti-
cally significantly more effective than placebo for SAR
symptom relief in children ages 6 –11 years. SAR symp-
tom improvement was not significantly different be-
tween the loratadine 10 mg and the placebo group.
ACKNOWLEDGMENT
The authors dedicate this manuscript to Anjuli Seth
Nayak, M.D. Anjuli was a renowned allergist and im-
munologist who ensured her patients received com-
passionate care. Additionally, Anjuli advanced cancer
research by endowing a professorship for leukemia
research at the University of Chicago Medicine. Dr.
O
Nayak chronicled her journey with acute lymphoblas-
tic lymphoma in her inspirational memoir, “Plucked
from a Mango Tree.”
N
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