1. Uveitis CTP
Egla Rabinovich, Sheila Angeles-Han, Drew Lasky and Mindy Lo
For the CARRA Uveitis working Group

2. Overarching goals of group
Develop consensus treatment plans (CTPs)
Obtain funding to implement CTPs via CARRAnet
Determine optimal treatment for pediatric uveitis

3. How is this CTP different?
Ophthalmologists are the ones who assess disease activity/damage, rheumatologist often the ones prescribing non-corticosteroid systemic medications.
2 ophthalmologists in group, uveitis experts (NIH and UCLA)
Topical (drops), injectable (periocular), and oral corticosteroids most often prescribed by ophthalmology and often before gets to rheumatology, especially in idiopathic AU.
We did not address any corticosteroid recommendations in terms of when to start DMARD

4. SUN* criteria for disease activity
Grade
Cells in Field 0^
0.5+
1-5 1+
6-15 2+
16-25 3+
26-50 4+
>50
^less than 1 cell per hpf is considered 0 cells
*Standardization of uveitis nomenclature

5. SUN Criteria for Response
Inactive
Grade 0 cells in anterior chamber
Worsening activity
Two step increase in inflammation by anterior chamber cells, or 3+ to 4+
Improved activity
Two step decrease in level of inflammation by anterior chamber cells, or decrease to 0
Remission
Inactive disease for ≥3 months after discontinuing all treatments for eye disease

6. Characteristics of patients eligible for CTP
Patients should have:
Anterior uveitis only: idiopathic or JIA-associated
<18 years old at enrollment
Refractory active uveitis, as evidenced by any of the following:
Ongoing uveitis activity, >1+ (6-15 cells/hpf) despite use of topical steroid drops
Worsening uveitis activity while on topical steroids
Recurrent disease (>1+) with taper of topical steroids to <BID
Development of new ocular complications* attributable to inflammation or treatment during topical therapy
Ask comments then show of hands
*Complications include: increased intraocular pressure, hypotony, cataracts, posterior synechiae, band keratopathy , hypopyon, cystoid macular edema.

7. Characteristics of patients not eligible for CTP
Patients should not have:
Panuveitis, intermediate, or posterior uveitis
Acute unilateral anterior uveitis
Retinal vasculitis
Active systemic infection or infectious uveitis
Uveitis associated with systemic disease other than JIA (eg. Behcet disease, sarcoidosis)
Contraindication to either methotrexate or anti-TNF therapy
Exposure to biologic therapy within prior 3 months
Ocular co-morbidity not due to uveitis
Corrected visual acuity <20/200 not due to active uveitis
Pregnancy
History of malignancy
Ask comments then show of hands

8. Clinical assessments at 0, 3, 6 mo or end of study
 Variables
Baseline
Follow Up
Disease duration
Age at disease onset
JIA subtype or idiopathic uveitis X
Uveitis
Anatomical Location
Laterality
Anterior chamber cells by SUN criteria
Visual acuity
Ocular complications
Ocular surgeries  X X 
PROs
VAS
Overall QOL: PedsQL
Uveitis related QOL: EYE-Q
Ask comments then show of hands

9. Outcomes Primary outcome: Secondary outcomes:
Improvement (SUN criteria) or worsening at 6 months as measured by presence of anterior chamber cells
Secondary outcomes:
Visual acuity
Eye complications
Eye surgeries
Ask comments then show of hands

10. End of study visit
If fail any study arm, either from disease activity/damage or intolerance to study medication
May reenter another CTP/study arm

11. DMARD naïve Uveitis Treatment Plan
Arm 1
Oral MTX
0.5-1 mg/kg/week, Max 30 mg
Eye exam by 6 weeks
Better: continue
Fail/intolerant: 1) Switch SQ or
2) Change to biologic uveitis CTP
Arm 2
SQ MTX
Fail/intolerant: Change to biologic uveitis CTP
sticky

12. Entry into biologic CTP - #1
Methotrexate CTP failures
>1+ anterior chamber cells and any of the following:
requirement for ongoing topical steroids >2 drops/day
no improvement, despite MTX for at least 3 months
worsening of, or development of new, ocular structural complications
(e.g., cataracts, band keratopathy, glaucoma, hypotony, cystoid macular edema)
Sticky for #1 and #2

13. Entry into biologic CTP - #2
MTX-naïve patients with active disease on presentation (>1+ AC cells) and at least one of the following:
1) ocular structural complications
2) intolerance to topical steroids
*Complications include: increased intraocular pressure, hypotony, cataracts, posterior synechiae, band keratopathy , hypopyon, cystoid macular edema.

14. Biologic* uveitis treatment plan
Arm 1
MTX PO/SQ + Adalimumab
Standard JIA dosing for Ada
Eye exam by 6 weeks
Better: Continue therapy
Fail: out of CTP
Arm 2
MTX PO/SQ + Infliximab
6 mg/kg rounded up vs.
6-10 mg/kg
Sticy dose and arms

15. Biologic* uveitis treatment plan
*Monoclonal antibody TNF inhibitor
New products that enter the market may be used in standard JIA dosing

16. Infliximab dosing
Initial infliximab dose should be 6 mg/kg rounded up vs mg/kg with loading doses at 0 and 2 weeks, followed by q 4 week dosing

17. Limited role of oral steroids
If oral steroids are used, they should be used only as bridging therapy while awaiting MTX or TNF inhibitor efficacy.
sticker

18. Monitoring recommendations
Children with active uveitis should be monitored by an ophthalmologist at least every 2-6 weeks; children with inactive uveitis on medications should be monitored a minimum of every 3-4 months.
Discuss and sticky