bachert2010

Safety and Efficacy of Desloratadine in
Subjects with Seasonal Allergic Rhinitis
or Chronic Urticaria
Results of Four Postmarketing Surveillance Studies
Claus Bachert
1
and Marcus Maurer
2
1 Department of Otorhinolaryngology, University Hospital Ghent, Ghent, Belgium
2 Department of Dermatology and Allergy, Charite
´-Universita
¨tsmedizin Berlin, Berlin, Germany
Abstract Background and Objective: Allergic rhinitis (AR) and chronic urticaria (CU)
are common diseases with symptoms that impair quality of life. Second-
generation antihistamines (e.g. cetirizine, desloratadine, fexofenadine,
loratadine and mizolastine) are recommended first-line treatment for both
conditions; however, studies of clinically relevant differences among these
agents are lacking. The aim of this investigation was to evaluate the safety,
tolerability and efficacy of desloratadine 5 mg once daily in four post-
marketing surveillance studies in subjects with seasonal AR (SAR) or chronic
idiopathic urticaria (CIU) in real-world clinical practice settings.
Methods: This programme of prospective surveillance studies was conducted
in Germany between February 2001 and March 2002 in allergy; dermatology;
ear, nose and throat; or general practice settings. Subjects (total number
77 880) were aged ‡12 years and met the requirements for treatment of SAR
or CIU with desloratadine as outlined in the package insert. All subjects
received oral desloratadine 5 mg once daily for a mean duration of up to
40.4 days. Adverse events (AEs) were reported throughout the studies; ser-
ious AEs were recorded for up to 30 days after treatment. Investigators and
subjects both rated tolerability at the end of treatment. Symptom severity and
sleep and daily activity impairment were evaluated at baseline and after
treatment using 4-point scales (0 =none; 1 =mild; 2 =moderate; 3 =severe).
Apost hoc subanalysis assessed desloratadine efficacy and onset of symptom
relief in subjects who had received monotherapy with another second-
generation antihistamine.
Results: A total of 386 AEs were reported by 287 subjects (0.37%) in the four
studies. The most commonly reported treatment-related AEs were fatigue
(0.07%), headache (0.07%), dry mouth (0.04%) and nausea (0.03%). Toler-
ability was rated as excellent/good by 99.1%of investigators and 98.5%of
subjects. Desloratadine therapy significantly reduced nasal and ocular
ORIGINAL RESEARCH ARTICLE Clin Drug Investig 2010; 30 (2): 109-122
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symptom severity, itching and wheals, and sleep and activity disruption
(p <0.0001), as indicated by a reduction in mean total and individual symp-
tom scores, and reported impairment of sleep and daily activities. The efficacy
of desloratadine was rated as significantly greater by 59.4–88.0%of subjects
who had previously received monotherapy with cetirizine, fexofenadine,
loratadine or mizolastine (p <0.01 for all). The percentage of subjects who
rated onset of symptom relief with desloratadine as faster than previous
treatment ranged from 51.6%to 82.4%.
Conclusion: Desloratadine was safe, well tolerated and efficacious in this
series of surveillance studies. A post hoc analysis of subjects who had received
previous monotherapy with a second-generation antihistamine found that
most subjects rated efficacy as higher than their previous treatment, with a
faster onset of symptom relief.
Background
Allergic rhinitis (AR) affects one in five people
worldwide.
[1]
The symptoms of AR –nasal con-
gestion; nasal itching; rhinorrhoea; sneezing;
itching, red and watery eyes; and itching throat
and palate –can impair sleep, work/school pro-
ductivity, learning and concentration, sig-
nificantly reducing quality of life (QOL).
[2-6]
In a
survey of 2966 adults with symptoms of rhinitis
randomly selected from five European countries,
German respondents (n =674) reported difficulty
sleeping (33%), problems with activities of daily
living (20%) and depression (31%).
[7]
Chronic urticaria (CU) is characterized by se-
vere pruritus, which can also be profoundly dis-
tressing and debilitating, causing QOL impair-
ment equal to that experienced by patients with
coronary artery disease.
[8,9]
Numerous studies
indicate that CU is associated with both psycho-
logical and physical impairment, including anxi-
ety, depression, decreased energy, disrupted
sleep, social isolation and difficulty with activities
of daily living.
[9-13]
Histamine is a key mediator in the symptomatic
expression of both AR and CU. Antihistamines,
which bind to histamine H
1
receptors, are very
effective for the treatment of these diseases.
[14,15]
Second-generation antihistamines lack the safety is-
sues, such as anticholinergic effects and somnolence,
associated with first-generation agents.
[16]
These
newer drugs, including cetirizine, desloratadine,
fexofenadine, loratadine and mizolastine, cause little
or no sedation and are not associated with clinically
relevant drug-drug interactions,
[15,17-22]
although
aluminium- and magnesium-containing antacids
may decrease fexofenadine absorption.
[23]
Treat-
ment guidelines recommend second-generation
antihistamines as first-line treatment for mild-to-
moderate and intermittent AR (IAR)
[24,25]
and for
CU.
[26]
Evidence for clinically relevant differences in
efficacy among second-generation agents is, at pre-
sent, limited.
[27]
Following the availability of the nonsedating
second-generation antihistamine desloratadine in
Germany in 2001, safety, tolerability and efficacy
data were collected prospectively in a series of
four postmarketing surveillance studies con-
ducted as mandated by y67.6 of the German Drug
Law (Arzneimittelgesetz). The results for the to-
tal subject population (n =77 880) of the four
studies are reported here. A post hoc subanalysis
of efficacy results for patients who had been
previously treated with second-generation anti-
histamine monotherapy is also included.
Subjects and Methods
Study Design
The four postmarketing surveillance studies
were conducted in Germany between February
2001 and March 2002 in adults and children aged
110 Bachert & Maurer
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‡12 years with seasonal AR (SAR) or chronic
idiopathic urticaria (CIU; CU of unknown aetiol-
ogy). The four studies evaluated the safety, toler-
ability and efficacy of desloratadine in allergy;
dermatology; ear, nose and throat; or general
practice settings. All subjects received deslor-
atadine (Aerius
, Schering-Plough, Kenilworth,
NJ, USA) 5 mg once daily. Additional medications
were allowed at the investigator’s discretion to re-
flect real-world clinical practice.
Subject Selection
Subjects met the requirements for treatment of
SAR or CIU with desloratadine as outlined in the
package insert. Subjects were excluded if they had
a history of sensitivity, allergy or adverse reaction
to desloratadine or its excipients. Pregnant or
lactating women were also excluded; pregnancy
(or pregnancy of the subjects’ partner) occurring
during the study was recorded.
Apost hoc analysis was conducted to assess the
efficacy and onset of symptom relief of deslor-
atadine in subjects who had previously received
monotherapy with a second-generation anti-
histamine (i.e. cetirizine, fexofenadine, loratadine
or mizolastine) for SAR or CIU. Subjects were
excluded from the post hoc analysis if they had
received previous treatment with two or more
medications for SAR or CIU.
The four studies were performed in ac-
cordance with the Declaration of Helsinki and
German national law. Case report forms de-
signed in conjunction with the requirements of
the German authorities were completed at each
study visit and included data on demographics,
disease signs and symptoms, previous treatment
history, and safety and efficacy assessments.
Safety and Tolerability Assessments
Investigators documented adverse events
(AEs) that were reported during treatment with
desloratadine regardless of causal relation. Mild
or moderate AEs were documented on a separate
form and were sent with case report forms to
DABIO (Ho
¨henkirchen, Germany). Serious AEs
(including death, hospitalization or pregnancy)
reported during or up to 30 days after deslor-
atadine treatment were recorded on specific re-
port forms and documented within a day of their
occurrence. Clinical events that did not result in
death, were not life threatening and did not re-
quire hospitalization were defined as serious AEs
if, according to the investigator’s assessment,
the event could jeopardize the patient and could
necessitate medical treatments to avoid the
above-described consequences.
Tolerability was assessed at the end of the pre-
scribed desloratadine treatment period by both
subjects and investigators on a 4-point scale (1 =
excellent; 2 =good; 3 =moderate; 4 =poor).
Efficacy Assessments
The primary efficacy outcome was the change
from visit 1 (baseline) to visit 2 (end of treatment)
in the total symptom score (sum of individual
symptom scores). Secondary efficacy parameters
varied with the study and included changes in
nasal, ocular, asthma or dermal and individual
symptom scores and the degree of SAR- or CIU-
disrupted sleep and daily activities at visit 2.
Subjects were assessed at visit 1 and visit 2. The
severity of individual symptoms was scored on a
4-point scale (0 =none; 1 =mild; 2 =moderate; 3 =
severe), and the scores were added together. Sub-
jects with CIU also reported the number of wheals
(0 =none; 1 =1–6 wheals; 2 =7–12 wheals; 3 =>12
wheals) and diameter of the biggest wheal (0 =
none; 1 =<1.25 cm; 2 =1.25–2.5 cm; 3 =>2.5 cm).
At visits 1 and 2, subjects scored the degree of
sleep disturbance (after 12am) and interference
with daily activity (after 12pm) caused by their
illness on a 4-point scale (0 =none; 1 =mild; 2 =
moderate; 3 =severe).
Subjects rated the efficacy of previous treatment
at visit 1 and desloratadine at study completion
using a 4-point scoring system (1 =excellent; 2 =
good; 3 =moderate; 4 =inadequate/poor). The rat-
ings for effectiveness in individual subject groups
were assessed as higher (+), equivalent (=)orlower
(-) scores for desloratadine versus previous treat-
ment. At visit 2, a 3-point rating scale (+1=faster
onset; 0 =equalonset;or-1=slower onset) was
used to assess the onset of symptom relief with
desloratadine compared with previous treatment.
Safety and Efficacy of Desloratadine 111
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Statistical Analysis
Data entered on case report forms were coded
into a database (Access; Microsoft Corporation,
Redmond, WA, USA) and assessed for incon-
sistencies using an electronic checking system.
Coding and data analyses were performed by
DABIO. The statistical significance of differences
in scores between visit 1 and visit 2 was analysed
using a Wilcoxon rank test; significance was de-
fined as p <0.05. The onset of symptom relief with
desloratadine versus previous monotherapy was
also evaluated by comparing subject assessments
in each previous treatment subgroup. Only sub-
jects with valid data for both assessments were
included in this analysis.
For symptom scores, the number of valid en-
tries, mean, standard deviation, and minimum and
maximum values were calculated. Frequencies and
percentages were calculated for categorical data.
Results
Demographics
Subjects (n =77 880) aged ‡12 years (mean
age, 40.8 years) were enrolled in the four post-
marketing surveillance studies; 58%of the overall
study population were female. Baseline demo-
graphics and clinical characteristics for the total
population and by individual study are listed in
table I.
Safety
A total of 287 subjects (0.37%) reported 386
AEs in the four surveillance studies during the
desloratadine treatment period (table II). Treat-
ment-related AEs were reported by 246 subjects
(0.32%); the most commonly reported were fati-
gue (0.07%), headache (0.07%), dry mouth
(0.04%) and nausea (0.03%). In the 41 subjects
whose AEs were not related to the study drug,
the most frequently reported AEs were nausea
(0.007%), headache (0.005%), dry mouth
(0.004%) and pharyngitis (0.004%). Two other
subjects each reported diarrhoea, fatigue and
rash (0.003%for each AE). The remaining 19
subjects reported one case each of abdominal pain,
amnesia, angina pectoris, asthenia, confusion,
coughing, dizziness, epistaxis, fracture, herpes
zoster, insomnia, malaise, migraine, myalgia, peri-
pheral oedema, rhinitis, sinusitis, taste perversion
and urinary tract infection (0.001%for each AE).
Overall, 166 subjects (0.21%) in the four studies
discontinued treatment because of an AE. Head-
ache (0.05%), fatigue (0.04%), nausea (0.03%)and
dry mouth (0.01%) were the most frequently
reported AEs causing cessation of treatment.
Dizziness, diarrhoea, abdominal pain, insomnia,
Table I. Subject demographics and clinical characteristics by individual study and combined
Demographic Study 1
(n =47 953)
Study 2
(n =9246)
Study 3
(n =7498)
Study 4
(n =13 183)
Total
(n =77 880)
Mean age (y) 38.8 43.2 39.2 42.1 40.8
Female (%) 57.8 62.5 56.3 57.1 58.0
Mean duration of desloratadine treatment [d (range)] 38.4 (1–232) 40.4 (1–238) 30.2 (1–233) 29.6 (1–240)
Type of practice Allergy, general Dermatology,
allergy, general
Ear, nose
and throat
General
Mean duration of allergy [mo (range)] 88.5 (1–840) 24.9 (1–600) 75.7 (1–720) 71.3 (1–600)
Diagnosis (%)
SAR
a
89.2 72.0 57.0
CIU 100 21.8
other 8.2 6.9 16.5
not recorded 2.6 21.1 4.7
a Includes subjects with a diagnosis of SAR plus other allergies.
CIU =chronic idiopathic urticaria; SAR =seasonal allergic rhinitis.
112 Bachert & Maurer
ª2010 Adis Data Information BV. All rights reserved. Clin Drug Investig 2010; 30 (2)

pharyngitis, somnolence, aggravated allergy, an-
gioedema and urticaria were also reported by
subjects who discontinued desloratadine treat-
ment. All AEs resolved after treatment was
discontinued. AEs and discontinuations from the
individual studies are listed in table II.
One subject in study 1 took desloratadine for
20 days during the second trimester of pregnancy
with no untoward effect on either mother or fetus;
the pregnancy continued to term successfully.
A 15-year-old female subject, also in study 1, with a
history of Gilbert’s disease, was hospitalized after
she developed nausea, vomiting and tachycardia
13 hours after the first dose of desloratadine; she
recovered fully.
Tolerability
In these four surveillance studies, 98.5%of
subjects rated desloratadine tolerability as ex-
cellent (76.9%) or good (21.6%); 0.5%of subjects
reported poor tolerance of desloratadine. Simi-
larly, 99.1%of investigators assessed the toler-
ability of desloratadine treatment as excellent
(80.4%) or good (18.7%); 0.4%of investigators
rated tolerance of desloratadine as poor. Figure 1
shows the tolerability of desloratadine as assessed
by investigators and subjects by individual study
and for the four studies combined.
Efficacy
Desloratadine therapy significantly reduced
the severity of the nasal and ocular symptoms of
SAR and the itching and wheals associated with
CIU (p <0.0001) in these four postmarketing
surveillance studies (figure 2). At visit 1, 14.3%,
12.1%and 10.5%of subjects reported no nasal
congestion, rhinorrhoea or sneezing/nasal itch-
ing, respectively (studies 1, 3 and 4). After treat-
ment with desloratadine, 54.0%, 61.8%and
62.8%, respectively, of subjects in these studies
had no nasal congestion, rhinorrhoea or sneez-
ing/nasal itching. In the same studies, 67.3%,
69.2%and 71.1%of subjects rated their conges-
tion, rhinorrhoea and sneezing/itching, respec-
tively, as moderate or severe compared with
6.5%, 4.9%and 4.7%, respectively, at study
completion.
The percentage of subjects reporting no der-
mal itching at visit 1 was 53.2%compared with
80.3%after desloratadine treatment (studies 1, 2
and 4). Dermal itching was rated as moderate or
severe by 30.1%of subjects in these studies at visit
1; at the end of the studies, moderate or severe
dermal itching was reported in 3.7%of subjects.
After desloratadine treatment, 76.2%, 71.5%
and 81.9%of subjects reported no ocular symp-
toms of tearing, burning/itching or flushing, re-
spectively; at visit 1, 19.5%, 16.7%and 24.6%,
respectively, had no ocular symptoms (studies 1
and 4). Tearing, burning/itching and flushing
were rated as moderate or severe in 51.7%, 57.1%
and 43.1%, respectively, at visit 1 in these studies
compared with 3.2%, 3.6%and 2.5%, respec-
tively, at study completion.
SAR- and CIU-impaired sleep and daily ac-
tivities also significantly improved (p <0.0001)
[figure 3]. The percentage of subjects in all four
studies who reported no sleep impairment in-
creased from 27.1%at visit 1 to 78.5%aftertreat-
ment with desloratadine. Similarly, at visit 1, 19.8%
of subjects reported no impairment of daily acti-
vities compared with 75.7%at the end of the study.
Study 1
The full results of study 1 in 47 953 subjects, of
whom 89.2%were diagnosed with SAR, have
been published previously.
[28]
In summary, both
Table II. Adverse events (AEs) and discontinuations by individual study and combined
Variable Study 1
(n =47 953)
Study 2
(n =9246)
Study 3
(n =7498)
Study 4
(n =13 183)
Total
(n =77 880)
AEs (n) 287 62 25 12 386
Subjects with AEs [n (%)] 212 (0.44) 43 (0.46) 23 (0.31) 9 (0.07) 287 (0.37)
Treatment-related AEs [n (%)] 190 (0.40) 31 (0.34) 17 (0.23) 8 (0.06) 246 (0.32)
Discontinuations due to AEs [n (%)] 130 (0.27) 22 (0.24) 11 (0.15) 3 (0.02) 166 (0.21)
Safety and Efficacy of Desloratadine 113
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