Article Text

FRI0559 Tocilizumab in the Treatment of Refractory Uveitis in Children
  1. S. Sukumaran,
  2. V. Vijayan,
  3. M.E. Elder,
  4. R. Modica
  1. Pediatrics, University of Florida, Gainesville, United States


Background Children with refractory uveitis present a unique therapeutic challenge as 50% - 75% of these children will develop significant visual impairment and treatment options are limited. Tocilizumab is a recombinant humanized IL-6 receptor antibody which blocks IL-6, an inflammatory mediator in the pathogenesis of uveitis. No studies exist regarding the role of this agent for management of refractory uveitis.

Objectives To evaluate the efficacy of the interleukin (IL)-6 receptor antagonist, tocilizumab in the treatment of uveitis in children refractory to methotrexate (MTX), mycophenolate (MMF) and long-acting tumor necrosis factor-α (TNF) inhibitors.

Methods Six children with refractory uveitis who received therapy with tocilizumab were included in this retrospective study. The main outcome measures included ocular outcome, reduction in concomitant immunosuppression and adverse events. Treatment efficacy was assessed by improvement in anterior chamber cell density (ACD), vitreous flare, intraocular pressure (IOP), visual acuity (VA), and ability to reduce or stop concomitant topical or systemic steroids.

Results All six children (12 eyes) had severe bilateral uveitis refractory to standard immunomodulatory agents and received tocilizumab intravenously every 2 weeks at doses of 12mg/kg for children <30kg and 10mg/kg for those ≥30 kg for 12 months. The age of onset of uveitis ranged from 2-17 yr (mean 7.6 yr), and the mean duration of uveitis at initiation of standard treatment was 1-12 yr (mean 4.8 yr). All patients had failed standard immunosuppressive therapies including prednisone (topical and systemic), MTX or MMF, and 5 children received ≥2 long-acting TNF inhibitors. All six children received a TNF inhibitors (infliximab or adalimumab) and 1 received abatacept for a mean of 31.6 mo (range 5-54 mo) prior to tocilizumab.

Twelve eyes (100%) of patients had active intraocular inflammation at baseline, and 7 eyes (58%) showed a decrease in ACD and 10 eyes (83%) showed a decrease in vitreous flare at the end of follow up (p<0.0001). Despite treatment with tocilizumab, one child continued to have multiple relapses. At baseline, visual acuity was ≤20/80 in 12 eyes but increased by ≥2 Snellen lines in 9 (75%) by the end of the study period and this was statistically significant (p<0.0001).

Preexisting complications of chronic uveitis and treatment were observed in 12 eyes and included cystoid macular edema (CME), increased IOP, cataract and synechiae. At the end of the follow up period, there was complete resolution of CME in 3/3 (100%) eyes, cataract resolved in 1 of 7 (14%) eyes. Four of 8 (50%) eyes with synechiae and 4 of 7 eyes (57%) with elevated IOP achieved normalization.

All 12 children received concomitant topical prednisone, oral/subcutaneous MTX and 2 children received MMF. One child had multiple relapses and required systemic steroids. At the end of follow up, we were able to reduce at least 50% of baseline immunosuppression in 11 children. Tocilizumab was well tolerated in all patients during the 12 month follow up period.

Conclusions Tocilizumab is an effective and well tolerated treatment option for children with chronic refractory uveitis. Use of tocilizumab was associated with improvement in ocular inflammation, visual acuity and reduction in concomitant immunosuppression. Further studies are needed to evaluate the role and safety of this agent in the management of refractory uveitis.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.3773

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