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Abstract Number: 417

Use of Tumor Necrosis Factor-α Inhibitors in Pediatric HLA-B27-Associated Uveitis

Bessie Frias1, Courtney McCracken2, Kirsten Jenkins3, Janet Figueroa4, Anna Tramposch1, Steven Yeh5, Purnima Patel4, Carolyn Drews-Botsch6, Sampath Prahalad7,8 and Sheila Angeles-Han2,7, 1Emory University, Atlanta, GA, 2Pediatrics, Emory University School of Medicine, Atlanta, GA, 3Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, 4Emory University School of Medicine, Atlanta, GA, 5Ophthalmology, Emory University School of Medicine, Atlanta, GA, 6Epidemiology, Emory University School of Public Health, Atlanta, GA, 7Children's Healthcare of Atlanta, Atlanta, GA, 8Pediatric Rheumatology, Emory University School of Medicine, Atlanta, GA

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: juvenile idiopathic arthritis (JIA), treatment and uveitis

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Session Information

Date: Sunday, November 13, 2016

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects - Poster I: Juvenile Idiopathic Arthritis, Uveitis

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:  Pediatric HLA-B27-associated uveitis is a common form of non-infectious uveitis (NIU) that can lead to ocular complications and vision loss.  Methotrexate (MTX) is the usual first-line systemic treatment in NIU.  Tumor necrosis factor-α inhibitors (TNFi) are primary therapy in other HLA-B27-associated diseases such as ankylosing spondylitis and inflammatory bowel disease. There is no standard treatment protocol for pediatric HLA-B27-associated uveitis.  Given the success of TNFi in other HLA-B27-associated diseases, our aim is to describe MTX and TNFi use in pediatric HLA-B27-associated uveitis.  

Methods: We reviewed medical records of 21 children with HLA-B27-associated uveitis.  We compared demographics and clinical characteristics based on treatment with TNFi.  

Results: There were 12 (57%) children with HLA-B27-associated uveitis alone (U), and 9 (43%) with JIA-associated uveitis (JIAU) that was all enthesitis related arthritis (Table 1).  Most were non-Hispanic (86%) White (95%) males (52%), diagnosed at a median of 10.5 (8.1-11.8) years, with anterior (90%), unilateral (67%) disease and several complications.  Of these, 14 (67%) did not require TNFi (8 topical steroids alone, 6 MTX alone,) and 7 (33%) required TNFi. There was a clinical trend of earlier treatment with TNFi in JIAU (0.5 vs. 2.6 years of MTX) despite similar uveitis duration before MTX start (0.2 vs. 0.3 years).  Comparing by TNFi use, more females were treated with TNFi (60% vs. 9%, p = 0.02) (Table 2). There was no difference in race, age at uveitis diagnosis, uveitis type, laterality, or complications.  Comparing by gender, more females 8/10 (80%) then males 5/11 (45%) also needed MTX. Although they had similar uveitis type (40% associated with ERA), complications (80%), and age at diagnosis (10.8 vs. 9.7 years), more females needed TNFi and MTX. 

Conclusion: Usual treatment for pediatric NIU includes MTX and then TNFi if MTX fails, ocular complications arise/worsen or uveitis persists. Based on our results, it appears reasonable to treat pediatric HLA-B27-associated uveitis with MTX prior to TNFi.  However, we demonstrate the increased use of TNFi in females despite a similar uveitis course. We were unable to determine clinical factors that explained this difference due to our sample size, but this requires further study. There may be an inherent gender difference in immune pathway response which may mitigate uveitis course and improve visual outcomes.  

Table 1. Demographics and Clinical Characteristics of Children with HLA-B27-associated Uveitis
  All (N=21) HLA-B27 associated uveitis alone  (U) (N=12) JIA-associated  uveitis (JIAU) (N=9) P-value**
Gender, female 10 (48%) 6 (50%) 4 (44%) 1.00
Hispanic 3 (14%) 1 (8%) 2 (22%) 0.55
Race*        
  Caucasian 20 (95%) 11 (92%) 9 (100%) 1.00
  African American 2 (10%) 2 (17%) 0 0.49
Age at Uveitis Diagnosis, years, median (25th – 75th) 10.5 (8.1-11.8) 9.1 (5.9-10.9) 11.6 (10.1-14.1) 0.11
Duration of Uveitis To Date, years, median (25th – 75th) 4.4 (2.0-5.9) 4.4 (2.8-5.9) 4.4 (1.6-5.9) 0.92
Bilateral Disease 7 (33%) 5 (42%) 2 (22%) 0.16
Location*        
     Anterior 19 (90%) 10 (83%) 9 (100%) 0.49
     Intermediate 5 (24%) 3 (25%) 2 (22%) 1.0
     Other (Panuveitis) 2 (10%) 2 (17%) 0 (0%) 0.49
Complications*        
      Any 17 (81%) 11 (92%) 6 (67%) 0.27
Synechiae 12 (57%) 9 (75%) 3 (33%) 0.09
Cataracts 6 (29%)  3 (25%) 3 (33%) 1.00
Cystoid Macular Edema 6 (29%) 3 (25%) 3 (33%) 1.00
Glaucoma/ Increased intraocular pressure 5 (24%) 4 (33%) 1 (11%) 0.34
Band Keratopathy 4 (19%) 2 (17%) 2 (22%) 1.00
Amblyopia 1 (5%) 0 (0%) 1 (11%) 0.43
Methotrexate Use, Ever 13 (62%) 6 (50%) 7 (78%) 0.37
        Maximum dose >0.5 mg/kg/week 12 (92%) 6 (100%) 6 (86%) 0.52
        Mode of administration, oral  7 (54%) 4 (67%) 3 (43%) 0.59
        Duration of Uveitis Before MTX, years, median (25th – 75t
h
)
0.2 (0.0-0.6) 0.3 (0.2-0.6) 0.2 (0-1.7) 0.87
Duration of MTX Before TNFi use, years, median (25th – 75th) 1.7 (0.4 – 3.6) 2.6 (1.0 – 5.6) 0.5 (0.0 – 1.9) 0.40
Adalimumab Use, Ever*** 2 (29%) 2 (50%) – –
        % on weekly 2 (100%) 2 (100%) –  
        Duration of Uveitis Before adalimumab, years, median (25th – 75th) 3.0 (2.1-3.8) 3.0 (2.1-3.8) –  
Infliximab Use, Ever*** 5 (71%) 2 (50%) 3 (100%) 0.43
        Duration of Uveitis Before infliximab, years, median (25th – 75th) 1.9 (0.5-2.2) 4.0 (0.5-7.5) 1.9 (0.3-2.2) 0.80
        Max Dose mg/kg, median (25th – 75th) 8 (7 – 10) 7.3 (7 – 7.5) 10 (8 – 10) 0.20
       Frequency every XX weeks, median (25th – 75th) 4.0 (4.0-4.0) 4.0 (4.0-4.0) 4.0 (2.0-4.0) 1.0

*Not mutually exclusive (‘select all that apply’): Race=one person identified as both races; Location= some patients have multiple locations of disease; Complications=some patients have multiple complications.

**Fisher’s exact tests for categorical data or non-parametric Wilcoxon rank-sum tests between U and JIAU , alpha=0.05, two-sided p-value.

*** Out of 7 total who were taking a TNFi.

 

Table 2. Comparison of Children with HLA-B27-associated Uveitis Treated with a Tumor Necrosis Factor α Inhibitor (TNFi)
  All (N=21) NO TNFi use (N=14) TNF use (N=7) P-value**
Gender, female 10 (48%) 4 (29%) 6 (86%) 0.02**
Hispanic 3 (14%) 2 (14%) 1 (14%) 1.00
Race*        
  Caucasian 20 (95%) 14 (100%) 6 (86%) 0.33
  African American 2 (10%) 1 (7%) 1 (14%) 1.00
Age at Uveitis Diagnosis, median 10.5 (8.1-11.8) 10.4 (6.5-11.8) 10.5 (8.1-13.5) 0.97
Duration of uveitis To Date, years, median (25th – 75th) 4.4 (2.0-5.9) 4.4 (0.9-5.9) 4.4 (2.0-7.2) 0.58
Bilateral Disease 7 (33%) 3 (21%) 4 (57%) 0.26
Location*        
     Anterior 19 (90%) 13 (93%) 6 (86%) 1.00
     Intermediate 5 (24%) 2 (14%) 3 (43%) 0.28
     Other (Panuveitis) 2 (10%) 14 (67%) 7 (33%) 1.00
Complications*        
Any 17 (81%) 11 (79%) 6 (86%) 1.00
Synechiae 12 (57%) 8 (57%) 4 (57%) 1.00
Cataracts 6 (29%) 4 (29%) 2 (29%) 1.00
Cystoid Macular Edema 6 (29%) 3 (21%) 3 (43%) 0.35
Glaucoma/ increased IOP 5 (24%) 3 (21%) 2 (29%) 1.00
Band Keratopathy 4 (19%) 3 (21%) 1 (14%) 1.00
Amblyopia 1 (5%) 1 (5%) 0 (0%) 1.00
*Not mutually exclusive (‘select all that apply’): Race=one person identified as both races; Location= some patients have multiple locations of disease; Complications=some patients have multiple diseases. **Fisher’s exact tests for categorical data or non-parametric Wilcoxon rank-sum tests between IU and JIA diseases, alpha=0.05, two-sided p-value.

 


Disclosure: B. Frias, None; C. McCracken, None; K. Jenkins, None; J. Figueroa, None; A. Tramposch, None; S. Yeh, None; P. Patel, None; C. Drews-Botsch, None; S. Prahalad, Novartis, 5,Medac pharma, 5; S. Angeles-Han, None.

To cite this abstract in AMA style:

Frias B, McCracken C, Jenkins K, Figueroa J, Tramposch A, Yeh S, Patel P, Drews-Botsch C, Prahalad S, Angeles-Han S. Use of Tumor Necrosis Factor-α Inhibitors in Pediatric HLA-B27-Associated Uveitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/use-of-tumor-necrosis-factor-%ce%b1-inhibitors-in-pediatric-hla-b27-associated-uveitis/. Accessed .
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