The Efficacy of Anti-TNF Alpha Agents in the Treatment of JIA- Associated Uveitis in a Pediatric Cohort
Phase: PHASE4
Conditions: Juvenile Idiopathic Arthritis Associated Uveitis
Sponsor: Kasr El Aini Hospital

 
 
 
 
 
 
Full Protocol 
Retrospective Analysis of the Use of Biologics for Juvenile Idiopathic 
Arthritis Related Uveitis in Abou El Reesh Pediatric Hospital, Cairo 
University 
 
 
 
 
 
 
 
 

 
 
Background and introduction 
 
Juvenile Idiopathic Arthritis (JIA) remains, globally, the most common systemic disorder 
associated with pediatric uveitis.  It accounts for approximately 75% of cases of pediatric anterior 
uveitis (AU) and affects around 30% of ANA positive JIA patients (regardless their type of 
arthritis.1. In a cohort study from the Cairo University Pediatric Hospital, JIA accounted for 39% 
of all cases of pediatric uveitis (unpublished data). 
  
The uveitis, being asymptomatic, chronic and often severe, leads to complications in a large 
number of patients.  Studies estimate that 28–67% of patients with JIA-associated uveitis 
develop ocular complications, with 12% developing poor visual outcome.  The main causes of 
poor vision were cataract, band keratopathy and macular edema.2 
 
The only means of improving long term effects of uveitis, is early and aggressive anti-
inflammatory treatment.3   
 
The main line of treatment of non-infectious causes of uveitis have been topical and systemic 
corticosteroids.  However, it is well known that their prolonged use often leads to ocular and 
systemic complications, especially in the pediatric age group. 4  
 
In 2019, the American College of Rheumatology/Arthritis Foundation recommended that in severe 
active chronic AU or in the presence of sight-threatening complications, methotrexate (MTX) and 
a monoclonal antibody TNFi should be administered immediately.  This is recommended over 
MTX as monotherapy.  They also recommended that inadequate response to one monoclonal TNFi 
at standard JIA dose, the dose and or frequency should be increased rather than switching to 
another monoclonal antibody TNFi.5 
 

Immunosuppressive drugs are used as steroid-sparing agents but are not free of complications.  
They increase the susceptibility of children to infection, may cause organ toxicity, reversible bone 
marrow suppression and may possibly lead to the development of malignancies.3 
 
Thus, our study aims to analyze the use of biologics in our hospital (Abou el Reesh, Cairo 
University) for children with JIA in controlling their ocular inflammation, prevention of the 
development of sight threatening complications and if this outweighs their potential associated 
side effects.  
 
Patients and methods 
Population of study & disease condition  
 
Retrograde analysis of data of all patients presented to Aboul Reesh uveitis clinic taking biologics 
from January 2017- January 2020.  In our hospital, the rationale for using biologics was a high 
frequency of sight-threatening, frequent recurrences of uveitis or intolerance to steroids or other 
immunosuppressive drugs, with severe adverse reactions. 
 
Sample size: 
 It is expected to review 250 patients files of Aboul Reesh uveitis clinic to find all JIA patients 
with ocular inflammation treated with biologics. 
 
Inclusion criteria 
1. 
Both genders 
2. 
Age up to 16 years 
3. 
Diagnosed JIA according to rheumatological criteria with ocular affection  
-Any type of arthritis (oligoarticular, polyarticular, systemic onset, ocular JIA) 
- ANA positive or negative 
      4. Uncontrolled uveitis or frequent relapses s  
 
Exclusion criteria: 
1.Patients without definitive diagnosis as JIA  

2. JIA patients on biologics without ocular affection (for systemic control) or with uveitis 
controlled without the use of biologics  
4.Patients without adequate duration for follow-up (less than 3 months) or lost follow up data 
5.Patients without available data prior to the start biologics (to compare control of the uveitis) 
               
      
 
             
Methodology  
  
Data will be obtained from by retrospective analysis of all files of patients with JIA from the Abou 
El Reesh ophthalmology outpatient clinic.   
 
The patients with ocular inflammation treated by biologics will be further analyzed.   
 
The data analyzed will divided into pre and post biologic treatment: 
 
In both we will document- 
-Baseline BCVA (in logMar notation) 
- Grading of ocular inflammation  
(Anterior chamber and vitreous cells were graded as +0.5, +1, +2, +3 and +4 according to the 
guidelines of the Standardization of Uveitis Nomenclature Working Group) 
- Number of relapses in one year 
- Development of sight threatening complication 
- Dose and frequency of systemic, regional and topical steroids 
- Other interventions required 
 
Treatment parameters to be analyzed include type, duration and dose of biologic agent used, time 
taken to reach inflammation control, adverse effects, and time taken to develop those adverse 
effects. 
 

Improvement or worsening of activity of inflammation was assessed according to the 
Standardization of Uveitis Nomenclature Group’s directions (2 step improvement or worsening of 
cells/flare)  
 
Treatment was determined as efficacious if one of the following was fulfilled: 
1. No relapses or decrease in the number of relapses 
2. Decrease in dose of topical or systemic steroids 
3. Improvement of BCVA of at least two lines 
Statistical analysis plan: 
 
All data will be entered into Excel spreadsheets (Microsoft Corporation, Redmond, WA, USA). 
All statistical analyses will be performed using IBM SPSS version 22.0 software (IBM Corp., 
Armonk, NY, USA). Descriptive statistics will be summarized as the mean ± standard deviation 
for numerical data, frequencies and percentages for categorical data. The ANOVA -test and 
Pearson moment correlation will be used to compare the means for the numerical data and to 
identify correlations between them. Chi-square test will be used to compare categorical data. P-
values ≤ 0.05 will be considered statistically significant. 
 
 
References 
1) Thorne E, Woreta F, Kedhar SK, Dunn and Douglas A. (2005) Juvenile Idiopathic 
Arthritis-Associated Uveitis: Incidence of Ocular Complications and Visual Acuity Loss. 
Am J Ophthalmol.143.840–846. 
2) Qian Y, and  Nisha R. (2010) Juvenile Idiopathic Arthritis Associated Uveitis. Curr Opin 
Ophthalmol . 21(6): 468–472. doi:10.1097/ICU.0b013e32833eab83 
3) Doycheva D, Deuter C, Stuebiger N, Biester S, Zierhut M. Mycophenolate mofetil in the 
Treatment of Uveitis 
in Children. (2007) Br J Ophthalmol. 91:180–184. 
doi:10.1136/bjo.2006.094698 
4) Chang P, Giuliari G, Shaikh M, Thakuria P, Makhoul D and Foster C. Mycophenolate 
Mofetil Monotherapy in the Management of Pediatric Uveitis.(2011) Eye 25, 427–435 

5) Sheila T. Han A,  Ringold S,  Beukelman T,  Lovell D, Cuello C, Becker M, Colbert R, 
Feldman B, Holland G, Ferguson P, Gewanter H, Guzman J. American College of 
Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and 
Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis. Arthritis & Rheumatology. 
(2019). 71(6): 864–877 
 
 
 
 
Retrospective Analysis of the Use of Biologics for  Juvenile Idiopathic 
Arthrtis Related Uveitis in Abou El Reesh Pediatric Hospital, Cairo 
University 
 
 
 
First version, 1st march 2020