Transcript Efficacy of Topical Azithromycin and Cyclosporine A (CsA) vs CsA

Efficacy of Topical Azithromycin &
Cyclosporine A(CsA) vs CsA Alone
in the Treatment of Dry Eyes
Associated with Blepharitis
Kenneth A. Beckman, M.D., F.A.C.S.
Disclosure: Author is a consultant for Inspire Pharmaceuticals, Inc. &
Allergan Pharmaceuticals, Inc.
Study Details
Pilot study, open-label
Single center
Study population: 23 patients with dry eyes and
blepharitis (19 patients completed the study)
Treatment: All patients applied CsA ophthalmic
solution twice a day for three months. The
Azithromycin group also applied Azithromycin
ophthalmic solution twice daily for two days followed
by once daily at bedtime for 28 days.
Clinical signs and symptoms were evaluated at
baseline, three weeks and three months.
Inclusion/Exclusion Criteria
Inclusion Criteria
Age > 18 years
Clinical diagnosis of blepharitis:
presence of lid hyperemia,
meibomian gland plugging,
thickened secretions, or debris
in the lashes
Clinical signs and symptoms of
evaporative dry eye: Tear
break-up time of less than ten
seconds in the worse eye,
conjunctival staining score at
least one out of four in each eye
Exclusion Criteria
Use of Azithromycin or CsA in
the previous six months
Allergy to either medication
Study Design
Azithromycin
CsA Alone
+CsA
Randomization
CsA Alone
Visit Schedule
Day 1
3 weeks
3 months
Safety and Efficacy Endpoints
Safety Measurements
-
Biomicroscopy and External Eye Exam
Best Corrected Visual Acuity
Adverse Event Monitoring
IOP
Efficacy Scores for the Clinical Signs and Symptoms
-
Fluorescein Tear Break-Up Time in seconds
Ocular Surface Disease Index(OSDI) scores
Conjunctival staining scores with lissamine green
Overall patient subjective assessment of the treatment at
the final visit
Table 1
Results - Conjunctival Staining
Azithromycin + CsA
CsA
(10 subjects)
(9 Subjects)
Mean (STD)
Observed
Change from baseline
Observed
p-value
Change from baseline
Visit 1
2.4 (0.94)
2.5 (0.88)
Visit 2
1.5 (0.77)
-0.9
(0.73)
37.5%
1.6 (0.59)
-0.9 (0.67) 36%
0.75
Visit 3
1.0 (0.56)
-1.4
(1.06)
58.3%
0.9 (0.64)
-1.6 (0.98) 64 %
0.74
• P-Values are for the treatment difference of change from baseline of conjunctival staining
using a mixed-effects linear model.
• These models adjusted for baseline (Visit 1) score. A random intercept is assumed for each
subject to account for the correlation between eyes.
Table 2
Results – TBUT
Azithromycin + CsA
CsA
(10 subjects)
(9 Subjects)
Mean (STD)
Observed
Change from baseline
Observed
p-value
Change from baseline
Visit 1
5.3 (3.05)
4.9 (2.65)
Visit 2
8.2 (4.27)
2.9
(2.87)
54.7%
7.3 (2.34)
2.4 (1.49) 49.07%
0.6
Visit 3
10.3 (4.12)
5.0
(2.89)
94.3%
8.3 (2.78)
3.4 (1.99) 69.4%
0.18
• P-Values are for the treatment difference of change from baseline of conjunctival staining using a
mixed-effects linear model.
• These models adjusted for baseline (Visit 1) score. A random intercept is assumed for
each subject to account for the correlation between eyes.
Table 3
Results – OSDI
Azithromycin/CsA
CsA
(10 subjects)
(9 Subjects)
Mean (STD)
Observed
Change from baseline
Observed
p-value
Change from baseline
Visit 1
46.6 (25.64)
53.6 (10.59)
Visit 2
20.1 (23.75)
-26.5 (21.45) 56.9%
33.5 (15.5)
-20.2 (19.67) 37.7%
0.26
Visit 3
13.2 (14.49)
-33.4 (19.63) 71.7%
26.8 (14.95)
-26.86 (20.37) 50.1%
0.095
•
P-Values are for the treatment difference of change from baseline of conjunctival staining using a
mixed-effects linear model.
•
These models adjusted for baseline (Visit 1) score. A random intercept is assumed for
each subject to account for the correlation between eyes.
Table 4
Patient Overall Rating of the Treatment
Overall Rating
Azithromycin/CsA
CsA
(n = 10)
(n = 9)
Excellent - 4
70%
0%
Good - 3
20%
56%
Fair - 2
10%
33%
Poor - 1
0%
11%
Worsening 0
0%
0%
3.6 (0.79) *
2.5 (0.70)
Mean (SD)
* p=0.005(WRST)
One patient in the CsA group rated 3.5. This was used to calculate the mean but was recorded as Good
for the above table.
Safety Results
Generally well tolerated
- One patient removed herself from the study
due to burning from CsA (5%)
- Three other patients removed themselves from
the study for personal reasons
Conclusions
For the treatment of dry eye disease associated with
blepharitis, this study found:
- A trend toward greater improvement in tear break-up
time with combined Azithromycin and CsA treatment
than CsA alone at 3 months (94% vs 69%, p=0.18)
- A trend toward greater improvement in OSDI scores
with combined Azithromycin and CsA treatment than
CsA alone at 3 months (73% vs 50%, p=0.095)
A statistically significant difference in the overall patient
satisfaction rating favoring the combined
Azithromycin/CsA treatment group (p=0.005).
90% of patients in the Azithromycin/CsA group rated
the treatment as excellent or good, while 44% of
patients in the CsA alone group rated the treatment as
fair or poor.
Conclusions
Both groups improved in a similar fashion in
conjunctival staining.
The small sample size may have limited statistical
significance of the results. The trends toward
greater improvement in tear break-up time and
OSDI with combined therapy along with the
significant difference in the patient satisfaction
survey warrant further investigation and
consideration for treating lid margin disease with
Azithromycin simultaneously while treating dry eye
disease with CsA.