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http://www.medscape.com/viewarticle/478997
Effect of Betamethasone-Loratadine Combination Therapy on
Severe Exacerbations of Allergic Rhinitis
A Randomised, Controlled Trial
J.R. Snyman; P.C. Potter; M. Groenewald; J. Levin
Clin Drug Invest 24(5):265-274, 2004. © 2004 Adis Data Information BV
Posted 06/08/2004
Abstract and Introduction
Abstract
Objective: Corticosteroids are effective in controlling the inflammatory component of allergic rhinitis;
however, evidence for the clinical efficacy of systemic corticosteroids in this disease is sparse. It is further
common practice to combine oral corticosteroids with antihistamines in the treatment of acute
exacerbations of allergic rhinitis. The aim of this study was to investigate the effect of low-dose oral
betamethasone alone and in combination with loratadine in a group of patients with allergic rhinitis with
clinically significant obstruction.
Methods: In this parallel, double-blind, active controlled multicentre study, 299 patients with severe
allergic rhinitis were randomly allocated to either betamethasone 1.0mg or betamethasone 1.0mg plus
loratadine 10mg or betamethasone 0.5mg plus loratadine 10mg or loratadine 10mg alone for 5–7 days.
Total symptom scores, nasal obstruction, and doctor and patient perception of improvement were
measured as markers of disease severity.
Results: Although not statistically significant, both betamethasone 1.0mg regimens resulted in a total
symptom score difference of at least 1 or more from loratadine (i.e. mean [SD] change in total symptom
score of 4.10 [3.10] and 4.40 [3.62] vs 3.10 [3.30], respectively, for betamethasone 1.0 mg plus
loratadine, betamethasone 1.0 mg and loratadine). All corticosteroid-containing regimens were
significantly better than loratadine alone with regard to the patients' (p < 0.013) and doctors' (p < 0.009)
perceptions of improvement. They significantly favoured loratadine in combination with betamethasone
over single-drug therapy (i.e. odds ratio: investigator ratings 0.49, 0.36 and 0.45, and patient ratings 0.47,
0.40 and 0.43, respectively, for 0.5 mg and 1.0 mg betamethasone plus loratadine and betamethasone
1.0 mg alone vs loratadine alone). Betamethasone 1.0mg plus loratadine also resulted in significant
reduction of the relapse rate compared with the other therapies.
Conclusions: This study demonstrated the benefit of a short course of a systemic low dosage of
corticosteroids with and without antihistamine therapy during acute severe exacerbations of allergic
rhinitis. Combination treatment with betamethasone 1.0mg and loratadine 10mg was significantly better in
relieving symptoms of hayfever as experienced by patients. This was the first study to give evidence of
benefit of systemic low-dose corticosteroids with and without an antihistamine in patients with acute
exacerbations of allergic rhinitis.
Introduction
Allergic rhinitis affects between 15% and 20% of the population, and seasonal exacerbations account for
significant morbidity in spring and summer.[1-3] Symptoms of allergic rhinoconjunctivitis that include
rhinorrhoea, nasal itching, sneezing, itchy eyes and tearing are mainly attributable to histamine release
from mast cells and respond significantly to antihistamine therapy. [2] Swelling and inflammation of the
nasal mucosa and subsequent nasal obstruction are due to the release of inflammatory mediators and
cytokines.[3] There is already extensive evidence linking allergic rhinitis and other inflammatory airway
conditions such as asthma, making effective treatment of allergic rhinitis a priority to prevent
complications and reduce their severity.[3]
Intranasal corticosteroids are effective in controlling the inflammatory component of allergic rhinitis. [1,4,5]
They are used to prevent the development of rhinitis symptoms during the pollen seasons. Clear effects
on the inflammatory cell component of the disease have also been demonstrated.[6] Evidence for the use
and clinical efficacy of systemic cortico-steroids for the treatment of rhinitis is, however, sparse.[4,7] It is
nonetheless common clinical practice to give short courses of systemic corticosteroids, often in
combination with numerous other drugs, to patients with severe exacerbations of allergic rhinitis during
the peak of the pollen season.[7] This is in line with international guidelines for treatment of atopic rhinitis in
patients with severe exacerbations poorly responding to other therapies, e.g. oral antihistamines, topical
corticosteroids and decongestants.[8,9] A single study reported the benefit of methylprednisolone acetate 6
mg/day on nasal blockage in a small dose-comparing study. In this study methylprednisolone 6mg did not
differ from 24 mg/day as far as blocked nose, itching and drainage were concerned. [10]
Although oral antihistamines such as loratadine have been extensively documented for their efficacy in
the treatment of seasonal and perennial allergic rhinitis,[11] they are less effective than topical
corticosteroids in relieving symptoms of nasal obstruction.[4,12]
The variable nature of seasonal exacerbations in chronic allergic rhinitis have led to the development of
guidelines recommending that treatment should be tailored to the severity of symptoms. [8,13]
Antihistamines such as loratadine have been shown to be corticosteroid sparing in some inflammatory
diseases such as asthma.[14] Very few such studies exist for rhinitis. In one study, loratadine in
combination with topical flunisolide improved symptom scores significantly more than flunisolide alone in
a condition typically treated with corticosteroids only, i.e. nonallergic rhinitis with eosinophilia.[15] One
unpublished study reported significant improvement in rhinitis symptoms and in markers of inflammation
when beta-methasone 0.75mg plus dexchlorpheniramine 6mg was compared with betamethasone
0.99mg, or dexchlorpheniramine 6mg alone. Study outcomes were stratified in such a manner as to make
overall interpretation almost impossible.[16]
Betamethasone is marketed in South Africa as a fixed-dose combination with an antihistamine,
dexchlorpheniramine (i.e. Celestamine® [Schering Plough, Isando, Johannesburg, South Africa],1
containing betamethasone 0.25mg and dexchlorpheniramine 2mg per tablet or 5mL syrup; dosing
schedule 1–2 tablets four times daily), with the registered indication of acute allergic rhinitis not
responding to conventional therapy.[17] We could not find any published data of efficacy in allergic rhinitis
for such a combination either as a combination or as separate components administered simultaneously.
The aim of this study was therefore to investigate the effect of these low doses of betamethasone in a
short-course combination with loratadine (one of the most commonly used nonsedating histamine H 1receptor blockers in South Africa) in a group of patients likely to respond to such a combination, i.e.
patients with moderate to severe allergic rhinitis with clinically significant nasal obstruction.
This regimen in a single morning low dosage and short duration of exposure to a systemic cortico-steroid
is considered to be safer than the current practice, i.e. multiple doses for 4 days. [17] Since adverse effects
of corticosteroids are dose and duration dependent, this regimen is considered safe, with transient effects
on the hypothalamo-pituitary-adrenal (HPA) axis and no long-term metabolic effects.[18]
1
The use of trade names is for product identification purposes only and does not imply endorsement.
Patients and Methods
Study Participants
In this parallel, double-blind, active controlled, multicentre study, 299 patients were enrolled. Medicines
were encapsulated and randomised numbers allocated by the sponsor. Patients therefore received two
capsules per day, i.e. either two active capsules or one placebo and one active capsule during the active
phase of the study, which was then followed by the placebo phase where patients only received single
placebo capsules. Patients were scored for severity of hayfever symptoms and nasal obstruction.
Patients aged over 12 years experiencing atopic rhinitis with seasonal exacerbations for two consecutive
seasons caused by aero-allergens (i.e. positive skin prick test of >3mm diameter or a positive
radioallergo-sorbent test [RAST] of >/=class 3 or >/=3.5 U/mL specific for tree and grass pollens) were
recruited for this study. The study was performed during the high grass pollen season in South Africa, i.e.
September to May, and patients with perennial symptoms had to have severe exacerbations due to these
pollens as specified.
The total symptoms score must have been >7 and the single symptom of nasal obstruction at least 2 for
the 2 days immediately prior to inclusion. Patients without significant eye symptoms were selected.
Patients had to be off the following medications prior to enrolment: 3 months for any topical or systemic
corticosteroids; 2 days for antihistamines (e.g. cetirizine, fexofenadine and ebastine); 2 days for
decongestants; 14 days for cromoglycate; 10 days for loratadine; and not on any other medication during
the study period. The washout period was deemed appropriate for all antihistamines except loratadine
(active metabolite), as their half-lives are less than 15 hours and with once-daily administration would not
have reached steady-state concentrations (>90% elimination by the end of a 48-hour period). The run-in
period was limited to 7 days. The study was performed in the spring-summer (2001–2002) pollen season
in South Africa.
Because of the severity of symptoms at inclusion the investigators believed that a placebo group was not
morally justifiable. It was also decided to administer betamethasone once daily in the morning to minimise
the effect on the normal rhythm of endo-genous cortisone production.[19]
Patients had to be otherwise healthy, and pregnant or breast-feeding women were excluded from
entering the study. Patients with other intermittent or chronic conditions related to atopy, such as active
eczema, food allergy or persistent asthma, were excluded.
The study was approved by the Faculty of Health Sciences Research Ethics Committees of the
Universities of Pretoria and Cape Town, as well as the South African Medical Association Research
Ethics Committee, and all patients had to sign informed consent prior to entry into the study. The study
was conducted in accordance with the Declaration of Helsinki (revised edition Somerset West, Republic
of South Africa, October 1996).
Allocation of Trial Medication
Patients were randomised to receive one of the following four oral treatment modalities:
betamethasone 0.5mg plus loratadine 10mg;
betamethasone 1.0mg plus loratadine 10mg;
betamethasone 1.0mg; or
loratadine 10mg.
Randomisation was carried out using random permuted blocks of size 8 and was stratified by centre.
Treatment began directly after reaching the predetermined severity score for at least 2 days prior to active
therapy. Active therapy was administered at about 8:00am for 5–7 days and was then followed by a
further 5–7 days of placebo treatment. The dosage of betamethasone 1mg was calculated to be almost
equivalent to prednisolone 7mg.[20] Safety for the selected population for the duration of treatment was
established in a previous study.[19] In this study it was established that short-course (5-day)
betamethasone 1mg treatment results in similar suppression of endogenous cortisol production to
prednisolone 10mg and that normal adrenal and HPA axis functions are established within 3 days after
discontinuation of therapy.
Safety Data
Physical examinations were performed on all participants to confirm compliance with inclusion and
exclusion criteria. Peripheral venous blood samples were collected at the screening visit and at visits 2
and 3 (i.e. before and after active therapy) to evaluate liver and kidney functions, to establish an initial
normal cortisol level, and to study the response to oral corticosteroid. Safety blood tests were repeated at
visit 4 only if deemed clinically indicated.
Evaluation of Outcomes
The primary objective was to document the possible superiority of low-dose betamethasone (i.e. 0.5 or
1.0mg) in combination with loratadine over single therapy with either drug (betamethasone 1.0mg and
loratadine 10mg) in relieving symptoms of allergic rhinitis (total symptoms score [TSS]). Secondary
outcome parameters were the patients' and physicians' perceptions of relief and the carryover effect
(sustainability after stopping therapy). An improvement difference of at least >1 TSS and an improvement
of at least 1 (scale 0–3) for nasal obstruction were argued to be of clinical value.
The total score of four symptoms of rhinitis, i.e. sneezing, rhinorrhoea, nasal pruritus and obstruction,
each evaluated on a scale from 0 to 3, made up the TSS. Scoring was done in the morning and evening
in a patient diary and the mean calculated for that day. Patients also had to judge efficacy daily on an
analogue scale to measure their perception of overall symptom improvement for that day. Furthermore, at
the end of the active and placebo treatment periods patients and doctors had to give their impression of
improvement on a 5-point ordinal scale; i.e. no, slight, moderate, marked and complete relief of
symptoms. Investigators also scored percentage nasal obstruction, using a predefined grid, judging
turbinates, as >90, 80, 60 or <60% for each nostril at the beginning and at the end of each observation
period. Investigators were trained to use the scoring system constantly.
Relapse or sustainability of medicine effect was evaluated by looking at the deterioration of the TSS as
well as the number of days taken for the TSS to deteriorate.
Statistical Analysis
The primary outcome measure for efficacy was the change in the TSS from baseline to the end of the
active phase. The change in TSS was analysed using an analysis of covariance approach (ANCOVA),
with model terms for site, treatment and baseline TSS (since the baseline TSS might affect the
improvement). Importantly, there was no evidence of a site-by-treatment interaction, so this interaction
term was not included in the model.
Orthogonal comparisons were made to decide which treatment arm was in fact responsible for the overall
treatment effect.[21] Treatment groups were specified before the trial was conducted; the following
contrasts were specified:
Contrast Set 1
(i) Betamethasone versus loratadine
(ii) Drug combinations versus single drug arms
(iii) Corticosteroid dose in drug combinations.
After a preliminary analysis of the data, it was found that the most important factor seemed to be whether
the corticosteroid betamethasone was present, and this led to a second set of contrasts being proposed,
namely:
Contrast Set 2
(i) Higher-dose betamethasone plus loratadine versus betamethasone alone
(ii) Lower-dose betamethasone versus higher dose
(iii) Any betamethasone versus loratadine alone.
Duncan's multiple range test, which gives the smallest difference between means that is statistically
significant at the 5% level, allowing for the number of means that are being compared, was used to
compare the treatment means.[21]
Thus for the change in TSS, the analysis was carried out using first the a priori contrasts, followed by the
new set of contrasts and finally Duncan's multiple range test.
In addition to the primary outcome, the following secondary outcome measures were analysed:
1. Improvement in the nasal blockage rating (investigator rating). This was compared between treatment
arms with a χ2 test, with Fisher's Exact Test as confirmation in case of sparse cells. For case of
comparison the following values were given to different percentages of obstruction: >90% = 1, 80% = 2,
60% = 3, <60% = 4, therefore allowing a maximum total score of 8 for both nostrils being less than 60%
blocked (the higher the value the smaller the turbinates).
2. The analogue scale for relief score completed by the patient on each day during the active phase of
treatment. The mean score was compared between treatment groups using a linear model with terms for
site, treatment and baseline TSS. The treatment arms were then further compared as described for the
change in TSS.
3. The degree to which any improvement was sustained is given by the increase in TSS from the end of
active treatment to the end of the following week; the higher this increase, the less relief has been
sustained. This was compared between treatment arms using a linear model with terms for site, treatment
and baseline TSS. In addition, the change in TSS from baseline to the end of the washout period was
calculated for each participant – the greater the change, the greater the long-term relief. This was also
compared between treatment groups for the change in TSS at the end of active treatment.
4. The extent to which participants sustained the benefit of treatment was further explored by measuring
the number of days to relapse and whether a patient relapsed. Relapse was defined as an increase in
TSS of at least 2 units on a given day, where the TSS did not subsequently reduce to within 2 units of the
score at the end of active therapy. Whether a patient relapsed was compared between treatment arms
using a χ2 test. The number of days to relapse was compared between treatment arms using a log-rank
test, and this was further explored by fitting Cox's proportional hazards regression model with terms for
site, treatment and baseline TSS. The two sets of contrasts as specified for change in TSS were also
examined.
5. The degree of relapse in the washout phase was also examined by looking at whether rescue
medication (Drixine®, Schering Plough, Isando, Johannesburg, South Africa) was used, and if so the
mean number of doses used. The comparison of whether rescue medication was used was done using a
χ2 test, with further analysis using logistic regression models.
6. At the end of the trial the investigator rated the patient's response on a five-point ordinal scale (1 =
complete relief, 5 = no relief or worse). These ordinal responses were compared between treatment arms
using a χ2 test. Further exploration was done using McCullagh's proportional odds regression model
(ordinal logistic regression).[22]
7. Similarly, the patient rated her/his response using the same ordinal scale and this was compared
between treatment arms using a χ2 test, with further analysis using ordinal logistic regression.
Results
Study Population
Two hundred and ninety-nine patients were enrolled according to the protocol, and of these, 11 were
excluded for per-protocol analysis. The excluded patients did not reach the required severity rating on
randomisation. The various treatment groups were well balanced for all relevant parameters with no
significant differences among them (see table I for baseline data).
Outcomes
Analysis of the main endpoints showed that, while not reaching statistical significance among the various
treatment groups, both treatment regimens containing betamethasone 1.0mg had a TSS difference from
loratadine alone of more than 1 (i.e. prespecified clinical importance). Corticosteroid-containing regimens
were also significantly better than loratadine alone (p < 0.015) [table II].
The symptom score for nasal obstruction alone did not differ significantly between groups at the end of
the actual treatment period.
Although nasal obstruction (i.e. doctors' evaluation of turbinate swelling) was improved in more patients in
the betamethasone 1.0mg plus loratadine group when compared with all other treatments, this also did
not reach the predetermined level of significance. In the study 43%, 53%, 49% and 41% of patients
improved, respectively, on betamethasone 0.5mg plus loratadine, betamethasone 1.0mg plus loratadine,
betamethasone 1.0mg, and loratadine.
Patients' perceptions of improvement as shown on a visual analogue scale of improvement demonstrated
significant and clinically meaningful differences. Patients on combination therapies (corticosteroid plus
antihistamine) fared significantly better (p = 0.03), and any corticosteroid-containing regimen was better
than loratadine alone (p = 0.016). Loratadine in combination with betamethasone was significantly better
than any single-drug therapy (p = 0.03) [table II].
The increase in TSS after the 1-week washout period was used as an indication of sustainability of effect
after only 1 week's therapy. Corticosteroid-containing regimens all demonstrated good improvement from
baseline (significantly different from baseline) [table II], thus allowing for relapse on stopping treatment
after 1 week of therapy. The effect of betamethasone on its own and also that of the low-dose
combination with loratadine were not sustainable (p = 0.005 and p = 0.039, respectively, for hazard ratios
from Cox regression). Beta-methasone 1.0mg plus loratadine 10mg was significantly better and good
symptom scores were retained during the placebo follow-on phase (no significant relapse).
Surprisingly, in spite of this significant difference in relapse rates, there were no significant differences in
the use of rescue medication among the treatment groups (p = 0.99).
Investigator rating of the relief obtained clearly indicated betamethasone 1.0mg plus loratadine as the
treatment with the best relief (table III). All corticosteroid-containing regimens were significantly better
than loratadine alone (p = 0.009). Overall patient rating of relief echoed this, also significantly favouring
the corticosteroid-containing therapies (p = 0.013). This parameter, however, demonstrated no significant
differences among the betamethasone regimens.
Adverse Events
Patient-reported adverse events did not differ among the groups. Betamethasone resulted in a significant
fall in morning cortisol after the active therapy phase. This was anticipated,[19] and only when deemed
clinically necessary were these levels repeated 7–10 days later; the latter plasma levels returned to
pretreatment levels at the end of the study period. No clinical signs of adrenal suppression occurred.
Discussion
This study demonstrated the benefit of adding systemic low dosages of corticosteroids (short course)
[betamethasone 1.0mg] to antihistamine therapy during acute severe exacerbations of allergic rhinitis.
Single-agent therapy also favoured betamethasone over loratadine 10mg alone. Combination treatment
with betamethasone and loratadine 10mg was significantly better in relieving symptoms of hayfever as
experienced by patients. This combination containing betamethasone 1.0mg also proved superior by
giving a more sustainable effect after stopping all therapy.
Intergroup differences with regard to the main study outcomes (difference in TSS change and nasal
obstruction score change) did not reach statistical significance. The final study size was underpowered to
demonstrate such a difference. The tendency for combination betamethasone 1.0mg and loratadine
10mg to improve TSS more than other therapies should be explored further in a follow-up study.
Corticosteroid-containing regimens were clinically and statistically superior to loratadine alone, with both
betamethasone 1.0mg-containing regimens demonstrating a difference of >1 TSS when compared with
loratadine alone.
Patients and doctors favoured the combination regimens, with all corticosteroid-containing regimens
being the preferred treatment, and also showed significant selection towards them on a visual analogue
scale of improvement.
These findings therefore support the general assumption that adding a short course of corticosteroid to
the initial therapy in patients with acute exacerbations of allergic rhinitis improves symptoms and wellbeing.[4,7] The TSS is perhaps too crude a parameter to determine patient responses to therapy as a single
measure of success. The development of various quality-of-life questionnaires is testimony to the
importance of patients' perceptions of benefit.[23,24]
In this study a rigid quality-of-life questionnaire was not used because it was argued that the short study
duration would have made the existing validated scoring systems not applicable in this particular
subgroup of patients. To compensate for this, the researchers included three other markers of perceived
benefit: a daily visual analogue scale of improvement to be scored by the patient, and again at the end of
the active treatment period a patient and doctor five-point scoring system of impression of improvement.
These softer (i.e. investigator and patient perceptions such as quality of life and visual analogue scales of
benefit) issues perhaps tell us more about symptom acceptability and improvement than a TSS in itself.
Allergic rhinitis is but one local manifestation of a systemic reaction of the immune response to the
environment. The lack of additional relief of obstruction with added beta-methasone was unexpected, as
this was believed to be the single most important additional benefit that could be added by the
corticosteroid.[4,10,25] Although the dose of corticosteroid was high enough to suppress adrenal
corticosteroid production, it was perhaps not sufficient to inhibit the local inflammatory response
significantly.[26,27] This is important, as a previous study already demonstrated the effect of
methylprednisolone 6mg on nasal obstruction versus placebo.[10] Furthermore, the anti-inflammatory
activity and HPA-axis suppression by corticosteroids parallel each other and therefore HPA-axis
suppression is perhaps a good measure of possible therapeutic effect.[28] The benefit of betamethasone
was therefore perhaps due to other effects of corticosteroids, e.g. inhibition of systemic cytokines with a
putative feeling of well-being. This may also be due to the significant tolerance to symptoms, such as
blocked nose, by individuals with chronic hayfever. This was perhaps best borne out by the fact that there
was no difference in the use of rescue decongestant medication during the placebo follow-on phase.
The initial exacerbation of allergic rhinitis is also known to be associated with a predominant local
vasodilatory response, which may not respond early to corticosteroid therapy. The present study
corroborates the findings by others who demonstrated significant benefit of an inhaled corticosteroid
(fluticasone) over an antihistamine (loratadine) alone.[27] These authors also indicated that combining a
corticosteroid with an antihistamine may have significantly more benefits in some domains of quality of life
compared with single corticosteroid therapy. Others demonstrated the lack of benefit of corticosteroids in
all domains of rhinitis scoring (itching, running nose and sneezing). [10] These are typically symptoms that
respond well to antihistamines.
Conclusion
In conclusion, this is the first study to provide evidence of benefit of a systemic short-course, low-dose
corticosteroid treatment in patients with acute severe exacerbations of allergic rhinitis.
Tables
Table I. Study Population Demographics and Baseline Parameters of Rhinitis
Treatment group
B(0.5)+L
B(1.0)+L
B(1.0)
L
72
73
73
70
29.9 (11.8)
33.1 (14.1)
29.3 (12.6)
29.4 (12.5)
0.23.
male
41
37
39
51
0.34
female
59
63
61
49
asthma
15
12
18
16
0.65
food allergy
3
7
5
5
0.65
eczema
9
6
10
10
0.62
76.1 (24.5)
72.8 (17.1)
71.3 (22.2)
71.0 (16.7)
0.41
n
Age (y) [mean (SD)]
p-Value
Sex (%)
Other diseases
Weight (kg) [mean (SD)]
Mean (SD) baseline symptom scores
TSS
9.98 (2.44)
9.85 (2.12)
10.17 (2.50)
9.91 (2.33)
0.85
nasal obstructiona
3.75 (1.31)
3.88 (1.43)
4.05 (1.46)
3.89 (1.26)
0.60
Swelling of turbinates: the higher the value the smaller the turbinates.
B(0.5)+L = betamethasone 0.5mg + loratadine 10mg; B(1.0)+L = betamethasone 1.0mg +
loratadine 10mg; B(1.0) = betamethasone 1.0mg; L = loratadine 10mg; TSS = total symptoms
score.
a
Table II. Symptom Improvement at the End of the Active Treatment Period
Treatment group
B(0.5)+L
B(1.0)+L
B
L
6.17 (3.28)a
5.61 (3.47)a
5.78 (3.10)a
6.72 (3.46)a
TSS
mean (SD)
mean Δ (SD)
3.81 (3.59)b
4.10 (3.10)b
4.40 (3.62)b
3.10 (3.30)
mean (SD)
4.93 (1.94)
5.39 (1.83)
5.66 (1.86)
4.96 (1.79)
mean Δ in score (SD)
1.19 (2.15)
1.51 (1.85)
1.61 (2.10)
1.07 (1.90)
patients improved (%)
43.1
53.4
49.3
41.4
4.58 (2.33)
4.83 (2.42)de
4.47 (2.29)e
3.93 (2.28)
Nasal obstructionc
Patient analogue scale for relief
mean (SD)
Significantly different from baseline (table I) [p = 0.05].
All corticosteroid-containing regimens (combined) significantly were better than loratadine (p =
0.015).
c
Swelling of turbinates: the higher the value the smaller the turbinates. Mean ? = change from
baseline as in table I.
d
Loratadine in combination with betamethasone was significantly better than both single-drug
therapies (p = 0.03).
e
Any corticosteroid-containing regimen was significantly better than loratadine (p = 0.016).
B(0.5)+L = betamethasone 0.5mg + loratadine 10mg; B(1.0)+L = betamethasone 1.0mg +
loratadine 10mg; B = betamethasone 1.0mg; L = loratadine 10mg TSS = total symptoms score; Δ
= absolute change in score from baseline.
a
b
Table III. Overall Investigator and Patient Rating of Relief
Treatment group
B(0.5)+L
B(1.0)+L
B
L
Patients with moderate to complete relief (%)
71.01
81.69
72.22
60.00
Odds ratio
0.49
0.36
0.45
1.0
p-Value
0.020
0.001
0.012
Patients with moderate to complete relief (%)
75.37
77.56
75.01
61.43
Odds ratio
0.47
0.40
0.43
1.0
p-Value
0.015
0.004
0.008
Investigator rating
Patient rating
B(0.5)+L = betamethasone 0.5mg + loratadine 10mg; B(1.0)+L = betamethasone 1.0mg +
loratadine 10mg; B = betamethasone 1.0mg; L = loratadine 10mg.
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Acknowledgements
The Claricort Study Group: P. Crossland, H. du Preez, I. Engelbrecht, K.C. Esterhuizen, E.J. Evans, M.
Groenewald, L.G. Herbst, R. Heitner, M.H. Hockman, D. Lakha, L. Leaver, H. Makan, W.E. Mans, P.C.
Potter, A.S. Putterman, G.J. Ras, C.J.B. Smit, J.R. Snyman, J. Steer, C.O. van Bergen, B.J. van der
Merwe, A. Viljoen.
Funding Information
The Claricort Study Group would like to thank Schering Plough (Pty) Ltd South Africa for their
sponsorship of this study and Mrs J. Bekker for secretarial support.
Reprint Address
Correspondence and offprints: Prof. J.R. Snyman, Department of Pharmacology, Faculty of Health
Sciences, University of Pretoria, PO Box 2034, Pretoria, 0001, South Africa. E-mail:
[email protected]
J.R. Snyman1, P.C. Potter2, M. Groenewald3, J. Levin4, for the Claricort Study Group
Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa,
Allergology Diagnostic and Clinical Research Unit, Department of Immunology, University of Cape Town,
Cape Town, South Africa, 3Department of Paediatrics, 1 Military Hospital, Pretoria, South Africa,
4
Biostatistics Unit, Medical Research Council of South Africa, Pretoria, South Africa
1
2
Disclosure: The authors have no conflicts of interest that may have influenced this study.
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