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ORIGINAL ARTICLE
ABSTRACT
Objective: To investigate oral nonsteroidal anti-inflammatory drug (NSAID) therapy in the
prevention of recurrences of uveitis in patients with recurrent nongranulomatous, idiopathic, or
HLA-B27-associated acute anterior uveitis (AAU).
Methods: Retrospective case series of 59 patients with recurrent AAU treated with celecoxib or
diflunisal.
Results: The average duration of NSAID therapy was 21.25.7 months. The average number of
relapses for all patients prior to systemic NSAID therapy was 2.84 per person-year follow-up. These
relapses declined to 0.53 per person-year follow-up with NSAID therapy (p <.001). The relapse
rates prior to and after treatment in the HLA-B27-positive group (n=21) were compared with the
relapse rates prior to and after treatment in the HLA-B27-negative group (n=38) and were also
statistically significant (p <.001).
Conclusion: Morbid attacks and the cumulative exposure to corticosteroids can be prevented with
systemic NSAID therapy in patients with recurrent AAU.
Keywords: anterior uveitis; nonsteroidal anti-inflammatory drugs; recurrent uveitis; inflammatory eye disease
116
Methods
The clinical records of 59 patients with a diagnosis
of recurrent acute anterior uveitis who presented to
MERSI between May 2005 and April 2008 were evaluated. All patients with recurrent, acute, and painful
attacks of uveitis and a follow-up period of at least
1 year prior to and after beginning the oral NSAID
therapy were included.
All 59 patients underwent standard screening tests
that are performed at MERSI on all patients with
uveitis. These investigations included tests for syphilis and HLA-B27 typing. All patients were examined
by the principal investigator (CSF) at all visits. Classification of uveitis was performed according to the
International Uveitis Study Group recommendations.18
Anterior chamber inflammation was graded as defined
by Foster and Vitale.19 According to the SUN working
group descriptions of uveitis, the attack was considered acute if it was sudden in onset and was limited
(less than 3 months) in duration.20 Patients with signs,
symptoms, and laboratory workup suggestive of
rheumatologic diseases were further evaluated by a
rheumatology consultation.
Multiple variables were assessed, including age at
onset, number and duration of attacks, associated systemic diseases, time and duration of topical corticosteroid use, and the time and duration of systemic NSAID
use. Recurrences of inflammation prior to commencing
NSAID therapy were recorded from the documentation
within chart notes of the patients obtained from the
referring physician, while those after the administration of NSAID therapy were recorded on examination
at MERSI as were the side effects while on NSAIDs.
Remission was defined as trace or absent inflammatory
cells in the anterior chamber while on systemic NSAID
therapy but off topical/systemic corticosteroid therapy
for at least 6 months. Systemic NSAIDs evaluated in
this study were celecoxib (Celebrex, Pfizer, New York,
NY) and diflunisal (Dolobid, Merck, Rahway, NJ).
Statistical analysis was performed using the Wilcoxon test to compare the differences of the relapses
prior to and during NSAID treatment. Mann-Whitney
test was used to compare the differences in follow-up
and remission between the following groups: celecoxib and diflunisal; HLA-B27 positive and negative;
and male and female groups. A p value of less than
.05 was considered to be statistically significant. This
study was approved by the Institutional Review Board
of the Massachusetts Eye and Ear Infirmary and was
performed in concordance with the Declaration of
Helsinki.
Results
The average age at presentation was 4311.7 years.
There were 26 male and 33 female patients. All 59
patients received systemic nonsteroid anti-inflammatory therapy for an average of 21.25.7 months.
Systemic autoimmune diseases were observed in 13
patients (11 female and 2 male): ankylosing spondilitis (n=4), juvenile idiopathic arthritis (n=2), psoriasis
(n=2), fibromyalgia (n=1), Hashimoto thyroiditis
(n=1), rheumatoid arthritis (n=1), and Crohn disease
(n=1).
All patients had a follow-up of at least 1 year prior
to commencing NSAID therapy. For the 59 patients, the
average number of relapses prior to systemic NSAID
therapy was 2.84 per person-year follow-up. Relapses
declined to 0.53 per person-year follow-up while on
NSAID therapy. The difference in the relapse rate was
highly statistically significant at p <.001. These data are
shown in Table 1.
The study patient group was divided on the basis
of gender (males=26; females=33) and reanalyzed. A
relapse rate of 2.73 in males and 2.94 in females prior
to NSAID therapy was found. This reduced to 0.53
in males and 0.57 in females after systemic NSAID
therapy was commenced. All patients remained in
remission for an average of 18.22 months. These data
are shown in Table 2.
The results were also analyzed based on the
patients who received celecoxib (n=30) versus those
who received diflunisal (n=29). Of the 30 patients who
received celecoxib, 26 received a 20-mg po bid dose
and the remaining 4 patients received 100mg po bid.
All of the patients on diflunisal received 500mg po
bid. The average follow-up for the celecoxib group
was 21.9 months. The rate of relapse prior to celecoxib therapy in that group was 2.73. This relapse
rate declined to 0.36 while the group was on cele-
Table 1 Follow-up, remission, and relapses prior to and during NSAID therapy for all patients
Relapses (prior to
Patients (N=59)
Follow-up (months)
NSAIDs)
Remission (months)
Average
21.23
2.84
18.22
STDEV
5.72
1.65
6.28
Note. STDEV, standard deviation. Relapses prior to and during NSAIDs therapy: p <.001.
2010 Informa Healthcare USA, Inc.
Table 3 Follow-up, remission, relapses, and side effects in patients with celecoxib and diflunisal
Follow-up
Relapses prior
Remission
Relapses dur(months)
to NSAIDs
(months)
ing NSAIDs
Celecoxib
Average
21.9
2.73
21.0
0.36
n=30
STDEV
4.87
1.46
5.50
0.67
Diflunisal
Average
18.56
3
15.34
0.7
n=29
STDEV
5.30
0.66
5.78
0.87
Statistic analysis
p=.027
p=.727
p <.001
p=.165
Note. STDEV, standard deviation; GI, gastrointestinal side effect.
8: GI
1: dysuria
1: drowsiness
Discontinued
NSAIDs
No
Side effects
1: GI
Yes
(n=5)
Relapses during
NSAIDs
0.24
0.44
0.66
0.88
p=.027
Discussion
Over the last 3 decades much has been discovered
about the mechanisms of action of a class of agents
collectively known as nonsteroidal anti-inflammatory
agents. These agents are widely prescribed in general
medicine for the treatment of rheumatologic diseases
and are principally used topically in ophthalmology for
the treatment and reduction of cystoid macular edema,
Ocular Immunology & Inflammation
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