Uveitis Clinical Trial
Official title:
Intravitreal Infliximab in Refractory Uveitis in Behcet's Disease: A Safety and Efficacy Clinical Study
Intravitreal injection of up to 2 mg of infliximab has proved to be safe in animal models
(rabbits and primates). These studies have shown no evidence of intraocular inflammation or
toxicity by clinical, electrophysiological, and histopathological examination for up to 90
days even with 3 repeated monthly injections. However, the study conducted by Rassi et al
was the only one to report the development of severe intraocular inflammation in one eye out
of 12 rabbit eyes at 90 days following 3 intravitreal injections (2mg monthly).
Unfortunately, clinical studies conducted on patients, so far, have raised serious concern
about its safety and adverse effects.
These clinical studies have shown various and inconsistent results in terms of the safety
and efficacy of intravitreal infliximab. These studies were conducted on patients with
refractory as well as naïve cases of age related macular degenerations choroidal
neovascularization (AMD CNV), diabetic macular edema (DME), central retinal vein occlusion
(CRVO), angiomatous malformations, pseudophakic macular edema, and uveitis. The doses used
ranged from 0.5mg to 2mg. The initial study by Theodossaidis et al in 2009 did not report
any intraocular inflammation in 3 patients receiving 2 intravitreal injections of 1 and 2 mg
for refractory AMD CNV with 7 months follow up period.(8) Later several clinical studies
have reported severe intraocular inflammation following intravitreal injections of
infliximab in non-uveitic patients.These collected data have initiated a call for cautious
use of intravitreal infliximab.
On the other hand, studies investigating intravitreal infliximab in uveitis patients have
shown improvement in vision, reduction in macular thickness on optical coherence tomography
(OCT), and reduction in inflammation. In this study, we have investigated the safety and
efficacy of 3 consecutive intravitreal infliximab injections (1 mg/0.05 mL, 6 weeks apart)
in carefully selected group of patients with refractory uveitis in Behcet's disease.
Approval of the study was obtained from the hospital's ethical committee. The study design
and methodology followed the tenets of Declaration of Helsinki. All patients were provided
with written informed consent and received a thorough explanation of the study design, aims,
and the off-label use of infliximab, its potential risks, and benefits. This is a
prospective non-comparative interventional study. The study was conducted on 20 eyes of 20
patients with refractory posterior uveitis in Behçet's disease who received 3 consecutive
intravitreal injections of infliximab (1 mg/0.05 ml) 6 weeks apart. Behçet's diseases was
diagnosed based on the International Criteria for Behçet's Disease (ICBD).
Patients were subjected to the following initial examinations: best-corrected visual acuity
(BCVA) measurement; slit-Lamp examination; measuring intraocular pressure (IOP) by Goldman
applanation tonometry; dilated fundus examination by indirect ophthalmoscope; and slit-lamp
biomicroscopy including vitritis grading (0-4) and presence or absence of vasculitis,
retinitis and papillopathy. Patients also had the following at baseline: fluorescein
angiography (FFA), ERG, and central foveal thickness (CFT) OCT (Stratus III OCT; Carl Zeiss,
Dublin, CA). Grading of vitritis was as follows: Grade 0: Good view of NFL (nerve fibre
layer), Grade +1: clear optic nerve & vessels but hazy NFL, Grade +2: optic nerve & vessels
are hazy, Grade +3: view of optic nerve only, and Grade +4: no optic nerve view.
Follow up clinical examinations were at day 1, and weeks 2, 4, 6, 8, 12 and 18. Each follow
up visit included: BCVA, slit-Lamp examination, IOP, dilated fundus examination with grading
of vitritis (0-4), and presence or absence of vasculitis, retinitis or papillopathy. CFT
OCT, and ERG were done at 4, 12 and 18 weeks. FFA was done at the discretion of the examiner
and not at every post-injection evaluation.
The intravitreal dose of infliximab used in this study is 1mg/0.05ml. Animal studies have
shown intravitreal infliximab in doses up to 2mg is safe clinically, and by
electrophysiological and histopathological examinations. These findings were maintained for
3 months with 3 monthly injections. However, in clinical trial severe intraocular
inflammation was elicited with even a single low dose of 0.5mg in non-uveitic eyes. Since
the 1 mg dose was shown to be effective in controlling inflammation in one study, we decided
to use this dose and avoid the 1.5mg and the 2mg doses.
Drug preparation: A vial containing 100 mg of commercially available infliximab powder
(Remicade Janssen Pharmaceutical Egypt) was reconstituted with 5 mL of sterile water, and
0.05 mL of this solution (1mg of infliximab) used for each patient and placed in a
tuberculin syringe using aseptic techniques. The remaining syringes will be kept in a
sterile package at 2-8ºC for 6 weeks.
Injection technique: The eye was prepared in a standard fashion using 5% povidone-iodine, an
eyelids speculum to stabilize the eyelids, and the injection of 1mg (0.05 mL) was performed
3.5mm to 4 mm posterior to the limbus, through the infero-temporal pars plana with a
30-gauge needle under topical anesthesia. After the injection, retinal artery perfusion is
checked and patients were instructed to administer topical antibiotics for 3 days. All
patients were given detailed post-injection instructions and asked to call promptly if any
pain or significant changes in vision occurred.
Patients were seen on follow ups and repeated injections were given at 6 weeks intervals if
re-injection criteria were met: 1) No evidence of significant ERG changes, 2) No evidence of
adverse effects to the drug, 3) Signs of anatomical and/or functional improvement during the
first 6 weeks.
Statistical Analysis: Data were statistically described in terms of mean ± standard
deviation (±SD), median and range, or frequencies (number of cases) and percentages when
appropriate. Comparison of numerical variables between the study groups was done using
Freidman's test with Conover test for paired (matched) samples as posthoc multiple 2-group
comparisons. For comparing categorical data, Chi square (±2) and McNemar tests were
performed. GCC was done using McNemar test. Agreement was tested using kappa statistic.
Correlation between various variables was done using Spearman rank correlation equation. P
values less than 0.05 was considered statistically significant. All statistical calculations
were done using computer program SPSS (Statistical Package for the Social Science; SPSS
Inc., Chicago, IL, USA) version 15 for Microsoft Windows Stats Direct statistical software
version 2.7.2 for MS Windows, StatsDirect Ltd., Cheshire, UK.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04101604 -
Biomarkers of Common Eye Diseases
|
||
Active, not recruiting |
NCT04704609 -
Imaging Quantification of Inflammation (IQI)
|
||
Completed |
NCT03173144 -
Chronic Inflammatory Disease, Lifestyle and Treatment Response
|
||
Withdrawn |
NCT01280669 -
Intravitreal Sirolimus as Therapeutic Approach to Uveitis
|
Phase 2 | |
Terminated |
NCT02907814 -
Measurement of Anterior Chamber Cell Grading Using Ocular Coherence Tomography
|
N/A | |
Active, not recruiting |
NCT02252328 -
Use of Simvastatin as a Steroid Sparing Agent for Uveitis Patients
|
Phase 2/Phase 3 | |
Completed |
NCT04183387 -
Simvastatin in Uveitis
|
Phase 2 | |
Completed |
NCT01983488 -
Clinical Outcome in Uveitis
|
||
Withdrawn |
NCT00499551 -
A Phase I/IIa Study for the Treatment of Uveitis With Iontophoresis
|
Phase 1/Phase 2 | |
Completed |
NCT00132691 -
Multicenter Uveitis Steroid Treatment (MUST) Trial
|
Phase 4 | |
Terminated |
NCT00114062 -
Study to Treat Uveitis Associated Macular Edema
|
Phase 2 | |
Completed |
NCT00476593 -
Retinal OCT and (mfERG) Related to Age, Sex, and the Use of Anti-inflammatory Medications
|
N/A | |
Completed |
NCT00001867 -
Effect of Pregnancy on Uveitis
|
N/A | |
Completed |
NCT00379275 -
Eye and Immunogenetic Features of Sarcoidosis
|
N/A | |
Active, not recruiting |
NCT03828019 -
Adalimumab vs. Conventional Immunosuppression for Uveitis Trial
|
Phase 3 | |
Terminated |
NCT01939691 -
Macular Edema Nepafenac vs. Difluprednate Uveitis Trial
|
Phase 4 | |
Active, not recruiting |
NCT03889860 -
Objective Choroidal Thickness Measurements in Uveitis
|
||
Completed |
NCT00070759 -
Daclizumab to Treat Non-Infectious Sight-Threatening Uveitis
|
Phase 2 | |
Recruiting |
NCT05486468 -
The Use of Two YUTIQ Versus Sham for Treatment of Chronic Non Infectious Intraocular Inflammation Affecting the Posterior Segment
|
Phase 3 | |
Active, not recruiting |
NCT05385757 -
UNICORNS: Uveitis in Childhood Prospective National Cohort Study
|