Background/Purpose

Chronic uveitis, an inflammatory eye disease, is a leading causes of childhood blindness and often has a chronic recurrent course. This study reviews the efficacy and safety of high dose (≥10-20 mg/kg) infliximab (IFX) in children with uveitis.

Methods

Retrospective chart review of 125 children and young adults with uveitis requiring systemic treatment. Data were collected on demographics, disease characteristics, infliximab dose, concomitant medications, treatment outcomes and side effects. Remission was defined as inactive eye disease ≥ 3 months after discontinuing all treatment; with ‘inactive disease’ was defined as grade 0 inflammatory cells. Descriptive statistics and Fisher’s exact were employed.

Results

Of 125 patients with uveitis, 33 (26.4%) were treated with high-dose IFX (≥10-20 mg/kg). An additional 19 patients received alternate TNF inhibitors (adalimumab 17(13.6%), etanercept 2 (1.6%)). The median age at diagnosis was 10 years (IQR 2,22), 76 (61%) were female. The ethnic distribution was 78 (62%) Caucasian, 26 (21%) Hispanic, 4 (4%) African American, 3 (1%) Asian, and 14 (11%) not specified. Uveitis was associated with JIA (JIA-U) in 62 (50%); 56 (45%) oligoarticular-JIA, 4 (4%) poly-JIA and 2 (2%) systemic-JIA. Forty-nine (40%) patients had idiopathic uveitis; other causes included sarcoidosis 6 (5%), tuberculosis 1 (1%), Behcet’s 1 (1%), Vogt-Koyanagi-Harada 1 (1%).

For the 33 patients on high-dose IFX, the median length of follow-up after initiation of treatment was 6 years, with a mean cumulative dose of 23 grams ± 16.7 (mean 7.2 mg/kg/dose ± 20.4).  Fourteen were first started on methotrexate (MTX) and topical steroids (TS) with a median time to initiation of IFX of 17 months (IQR 7, 26), 12 were started on MTX and IFX simultaneously, and 7 received IFX monotherapy. Twenty-one (64%) achieved inactive eye disease, while 12 (36%) had persistently active disease. Of 73 patients treated with MTX/TS alone, 23 (32%) had inactive disease while 50 (68%) were active at last visit, showing increased inflammatory ophthalmic disease in patients not on IFX (p<0.0013). This difference was maintained when comparing all 52 patients on TNF inhibitors to those on MTX alone, 33 (63%) of patients on TNF inhibitiors had inactive  disease compared to 23 (32%) on MTX (p<0.0005).

Ophthalmologic complications of uveitis included band keratopathy in 13 (10%), cataracts in 9 (7%), posterior synechiae in 8 (6%), and glaucoma in 4 (3%). The majority of complications were seen prior to starting IFX. No significant differences were seen between patients on IFX and those on MTX.

No malignancies or serious infections requiring hospitalization were seen in these patients. One patient on adalimumab developed dilated cardiomyopathy and 1 herpes zoster. At the end of study, 28 (85%) patients remain on IFX and 3 on adalimumab, 1 on etanercept and 1 on leflunomide/rituximab.

Conclusion

This is the largest study assessing the efficacy and safety of high-dose infliximab in the treatment of pediatric uveitis. Our data demonstrate favorable outcomes in patients on IFX, with 64% achieving inactive disease vs 32% on MTX. Extended use of high-dose infliximab did not appear to be associated with increased risk of serious infection or malignancy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-high-dose-infliximab-in-the-treatment-of-uveitis-in-pediatric-patients/