P2085
Efficacy of flurbiprofen 8.75 mg lozenges for streptococcal and non-streptococcal
sore throat: pooled analysis of two randomised, placebo-controlled studies
Shephard A, Smith G, Aspley S, Schachtel B
1
1
1
2,3
Reckitt Benckiser Healthcare International Ltd, Slough, Berkshire, UK; 2Dept. of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA; 3Schachtel Research Company, Jupiter, Florida, USA
1
Group A β-haemolytic streptococcus (Strep A) is responsible for
approximately 10% of sore throats in adults1
Item
0 Point
Oral temperature
≤98.6ºF
Oropharyngeal colour
Normal/
pink
Slightly
red
Red
Normal/
absent
Slightly
enlarged
Moderately
enlarged
Much
enlarged
None
Few
Several
Many
Strep A is the only commonly occurring bacterial infection associated
with a risk of suppurative and non-suppurative complications, so
antibiotic treatment may be warranted2,3
Size of tonsils
However, the risk of complications is low so accurate diagnosis
of Strep A is important to prevent inappropriate antibiotic use2–4
Number of oropharyngeal
enanthems (vesicles,
petechiae or exudates)
Other bacterial causes of sore throat include group C or G β-haemolytic
streptococci (Strep C or G), but there is insufficient evidence that these
infections cause complications2
There is a broad overlap between the signs and symptoms of
streptococcal and non-streptococcal sore throat, making rapid
diagnosis based on physical features difficult4
In the absence of a throat culture to diagnose streptococcal infection,
practitioners often rely on clinical findings to make a presumptive
diagnosis and begin treatment with an antibiotic
A throat culture can take 24–48 hours or longer to obtain results2
Therefore, non-antibiotic sore throat treatment may benefit patients
before definitive culture results are available
We investigated the effectiveness of a single dose of flurbiprofen 8.75 mg
lozenge in adults with acute sore throat before culture results were obtained
METHODS
Study design
Pooled analysis of two randomised, double-blind, placebo-controlled,
parallel-group studies:
A single-centre study at a US university health centre (NCT01049334)
A multi-centre study at four US research centres (NCT01048866)
Study population
The studies included adults (≥18 years) with recent onset sore
throat (≤4 days)
Inclusion criteria included moderate or severe pain on the Throat Pain
Scale (categorical scale), ≥1 symptom of upper respiratory tract infection
(URTI) on the URTI Questionnaire, a score ≥5 on the Tonsillo-Pharyngitis
Assessment (TPA; index of objective features of pharyngitis; Table 1)5,6
In addition, patients had to rate their symptoms on three different
100-mm visual analogue scales (VAS)7 as follows:
≥66 mm on the Sore Throat Pain Intensity Scale (STPIS; 0=no pain,
100=severe pain)
≥50 mm on the Difficulty Swallowing Scale (DSS; 0=not difficult,
100=very difficult)
≥33 mm on the Swollen Throat Scale (SwoTS; 0=not swollen,
100=very swollen)
Largest size of anterior
cervical lymph nodes
Normal
Number of anterior
cervical lymph nodes
Normal
Maximum tenderness of
some anterior cervical
lymph nodes
Not
tender
1 Point
2 Points
98.7–98.9ºF 99.0–99.9ºF
3 Points
≥100.0ºF
Beefy red
Slightly
enlarged
Moderately
enlarged
Much
enlarged
Slightly
increased
Moderately
increased
Greatly
increased
Slightly
tender
Moderately
tender
Very
tender
Study medication
Patients were randomised to receive one sugar-based, flavoured
flurbiprofen 8.75 mg lozenge or one sugar-based, flavoured, matching
vehicle lozenge (placebo)
Study assessments
The practitioner made several assessments at baseline, including:
Clinical Assessment of Strep Throat (CAST; categorical scale indicating
the likelihood of group A streptococcal infection: unlikely, uncertain,
likely, very likely)
Practitioner’s Assessment of Inflammation (PAIN; categorical scale
indicating the severity of pharyngeal inflammation: none, mild,
moderate, severe)
Throat cultures and Rapid Strep Tests were conducted at baseline to
detect streptococcal throat infections; antibiotics were offered the
following day (~24 hours post first dose of study medication) to patients
with laboratory-confirmed streptococcal infection
Patient population
A total of 402 patients were randomised to receive flurbiprofen 8.75 mg
lozenge (n=203) or placebo lozenge (n=199)
Treatment groups were well balanced in terms of demographic and
clinical baseline characteristics (Table 2)
46.5% of patients had moderately or much enlarged tonsils
(on the TPA)
All patients had some evidence of pharyngeal inflammation
(on the PAIN); 63.4% of patients had evidence of moderate or
severe pharyngeal inflammation
401 patients were assessed by the CAST; 85/401 (21.2%) were
considered likely or very likely to have Strep A
Table 2. Baseline demographics and characteristics
Flurbiprofen 8.75 mg
(n=203)
Overall
(n=402)
Age, mean (SD), years
26.6 (10.4)
26.8 (10.7) 26.7 (10.5)
STPIS, mean (SD), mm
78.9 (8.3)
79.8 (8.2)
79.4 (8.2)
TPA score, mean (SD)
8.8 (2.6)
9.1 (2.9)
9.0 (2.8)
TPA – size of tonsils, %
Normal
Slightly enlarged
Moderately enlarged
Much enlarged
17.2
37.9
33.5
11.3
18.1
33.7
34.2
14.1
17.7
35.8
33.8
12.7
PAIN, %
Mild inflammation
Moderate inflammation
Severe inflammation
36.9
54.2
8.9
35.9*
53.5*
10.1*
36.4
53.9
9.5
CAST, %
Unlikely
Uncertain
Likely
Very likely
34.0
47.3
16.7
2.0
32.3*
43.9*
22.2*
1.5*
33.2
45.6
19.5
1.7
*n=198 as one patient in placebo group was not assessed
CAST, Clinical Assessment of Strep Throat; PAIN, Practitioner’s Assessment of Inflammation;
SD, standard deviation; STPIS, Sore Throat Pain Intensity Scale; TPA, Tonsillo-Pharyngitis Assessment
All adverse events (AEs) were recorded
Diagnosis of streptococcal sore throat
STPIS data were pooled from the two studies to determine the mean
change from baseline in STPIS score during the 6 hours post dose
To assess the efficacy of a single dose of study medication, for patients
who used additional medication, all following changes in STPIS values
over 6 hours were set to zero according to the baseline observation
carried forward (BOCF) convention
Efficacy was calculated using least square (LS) means and analysis of
variance (ANOVA) was used to compare flurbiprofen 8.75 mg and
placebo groups with the relevant baseline included as a covariate
Two-sided statistical tests were performed with significance determined
by reference to the 5% significance level
Wilcoxon rank sum tests were performed to analyse the data obtained for
the inflammation category (on the PAIN) and size of tonsils (on the TPA)
Chi-square tests were used to compare the number of AEs in the two
treatment groups
Poster presented at the 23rd European Congress of Clinical Microbiology and Infectious Diseases, 27–30 April 2013, Berlin, Germany.
This study was funded by Reckitt Benckiser. Editorial assistance was provided by Elements Communications Ltd (Westerham, UK) and funded by Reckitt Benckiser.
The practitioners were uncertain of the likelihood of Strep A in 183/401
(45.6%) of patients (Tables 2 and 3)
Overall, 401 patients had a throat culture test; 40/401 (10.0%) were
positive for Strep A, 56/401 (14.0%) were positive for Strep C, and no
patients had both Strep A and C (Table 3)
Of the 85 patients whom the practitioners considered likely or very likely to
have Strep A, 84 had a throat culture test: 22/84 (26.2%) were found to be
positive for Strep A or Strep C (Table 3)
Of the 40 patients positive for Strep A on culture, 11 were correctly
diagnosed on clinical grounds of the CAST (i.e., a sensitivity of 27.5%)
Of the 361 patients not positive for Strep A, 360 were assessed by the CAST,
and of these 360 patients, 128 were correctly diagnosed by the practitioner
on the CAST as unlikely to have Strep A (i.e., a specificity of 35.6%)
Of the 85 patients who were considered likely or very likely to have Strep A
on the CAST, 84 had a throat culture, and 11 (13.1%) of these 84 patients
were positive for Strep A: a false-positive rate of 86.9% (these patients
would have been unnecessarily treated with antibiotics on clinical grounds)
CAST results, n
Unlikely Uncertain Likely Very
Not
Overall, n
likely assessed
Strep A +ve
5
24
10
1
–
40
Strep A -ve
88
102
52
4
–
246
Strep C +ve
10
35
10
1
–
56
Other*
30
22
5
1
1
59
Not assessed
–
–
1
–
–
1
133
183
78
7
1
402
Overall, n
Placebo
(n=199)
0
Table 3. Laboratory diagnosis (on throat culture) and practitioners’
assessments of streptococcal sore throat (on the CAST)
Throat culture
results, n
Patients rated sore throat pain on the STPIS at baseline and during the
6 hours post treatment
Statistical analysis
b) Patients with non-streptococcal sore throat
Of the 56 patients who were positive for Strep C on culture, 11 (19.6%)
were diagnosed on the CAST as likely or very likely to have Strep A (and
would also have been treated with antibiotics on clinical grounds)
LS mean of change in STPIS score
from baseline, mm
The vast majority of acute sore throats are viral in origin but a small
proportion are caused by bacteria1–4
RESULTS
Table 1. Tonsillo-Pharyngitis Assessment (TPA)
0
1
Time since dose (hours)
2
3
4
5
-5
-10
-15
-20
-25
Flurbiprofen 8.75 mg (n=150)
Placebo (n=156)
-30
Safety
The percentage of patients who reported any AE during the 6-hour
treatment period were as follows for the flurbiprofen 8.75 mg and placebo
groups, respectively:
Efficacy of flurbiprofen 8.75 mg lozenge compared with placebo
A single dose of flurbiprofen 8.75 mg provided greater reduction in sore
throat pain than placebo in patients with or without laboratory-confirmed
streptococcal sore throat (Figures 1a and b)
Streptococcal sore throat: 18.9% and 23.3%
Non-streptococcal sore throat: 16.7% and 14.7%
ANOVA results indicated statistically significant pain reduction by
flurbiprofen 8.75 mg compared with placebo at:
There were no serious AEs in either group
2 and 3 hours post dose for patients with streptococcal sore throat
(both p<0.05)
DISCUSSION
1, 2, 3 (all p<0.0001), and 4 hours (p<0.01) post dose for patients
with non-streptococcal sore throat
Diagnosis of streptococcal throat infection is difficult based on patient
history and physical examination alone
These data (Figures 1a and b) indicate that the pharmacological effect of
a flurbiprofen 8.75 mg lozenge was similar among patients with or without
streptococcal infection
This study shows that adult patients with streptococcal or nonstreptococcal sore throat obtain symptom relief from a single dose of
flurbiprofen 8.75 mg lozenge, obviating the need to initiate antibiotic
therapy without a culture-proven diagnosis
These data also indicate that this effect has a definite duration of action (i.e.,
relief has an onset, peak, and decline over time, when sore throat pain recurs)
and, therefore, does not “mask” the symptoms of streptococcal sore throat
Figure 1. Change in sore throat pain following a single dose of study
medication in a) patients with laboratory-confirmed streptococcal sore
throat and b) patients with non-streptococcal sore throat
0
0
1
5
Flurbiprofen 8.75 mg lozenge is a rational therapeutic alternative to
antibiotics before the practitioner has the results of a throat culture
CONCLUSION
a) Patients with laboratory-confirmed streptococcal sore throat
Time since dose (hours)
2
3
4
6
LS, least square; STPIS, Sore Throat Pain Intensity Scale
*41 = normal flora; 5 = non-Strep A; 5 = Strep B; 2 = Staphylococcus aureus; 2 = tests improperly
submitted; 3 = Strep G; 1 = Strep B and G
CAST, Clinical Assessment of Strep Throat
LS mean of change in STPIS score
from baseline, mm
INTRODUCTION
6
A single dose of flurbiprofen 8.75 mg lozenge provides
safe and effective pain relief for both streptococcal
and non-streptococcal sore throat but does not
“mask” a streptococcal infection
-5
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-10
-15
-20
-25
-30
Flurbiprofen 8.75 mg (n=53)
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