Adalimumab in the therapy of uveitis in childhood

Abstract

Purpose: Chronic anterior uveitis in children often takes a serious course. Despite various immunosuppressive drugs some children do not respond sufficiently and there is a high risk of them becoming seriously disabled. Anti-TNF alpha therapy has been shown by our group and others to be mostly ineffective (Etanercept) or partly effective (Infliximab) with the risk of anaphylactic reactions. Here we report on 18 young patients treated with Adalimumab (HumiraH), a complete humanised anti-TNF alpha antibody. Methods: We retrospectively analysed 18 patients, who were treated with Adalimumab (20-40 mg, every 2 weeks, when ineffective every week); 17 had juvenile idiopathic arthritis, one was without detectable underlying disease. The age at onset of arthritis varied from 0.5-15 years and for uveitis from 2-19 years. Patients were included when the previous anti-inflammatory therapy had been ineffective. It consisted of systemic steroids (n = 18), Cyclosporin A (n = 18), Methotrexate (n = 18), Azathioprine (n = 12), Mycophenolate mofetil (n = 4), Cyclophosphamide (n = 2), Leflunomide (n = 3), Etanercept (n = 8) and Infliximab (n = 5). The grading for uveitis was: (a) effective: no relapse or more than two relapses less than before treatment, (b) mild: one relapse less than before treatment, (c) no response: no change in relapse rate and (d) worsening: more relapses under treatment than before. The grading for arthritis (depending on the clinical findings), using three out of six parameters of the ACR PED Criteria, was: effective, mild, no response, worsening. Results: For arthritis (n = 16) the response to Adalimumab was effective in 10 of 16 patients, mild in three patients, three did not respond. For uveitis (n = 18) Adalimumab was effective in 16, mild in one child, and one patient did not show any effect. After a very good response initially a shorter application time had to be used to maintain the good anti-inflammatory effect in one child. Additional immunosuppressive treatment was used in seven of the effectively treated children. Due to elevation of liver enzymes in one patient, who also took MTX, Adalimumab had to be discontinued. No anaphylactic reactions or increased frequency of infections since start of Adalimumab treatment was reported. Conclusions: For our group of children with long lasting disease our results show that Adalimumab was effective or mildly effective against the arthritis in 81%, but in uveitis in 88%. While these results regarding arthritis are comparable with other TNF-alpha blocking drugs (Etanercept), Adalimumab seems to be much more effective against uveitis than Etanercept. Anaphylactic reactions, found in a previous study from our group after Infliximab treatment, were not seen with Adalimumab. The necessary dosage and the treatment period, which probably have to be defined individually for each patient, remain unclear.

Do tumor necrosis factor inhibitors cause uveitis? A registry‐based study

“…An analysis of ankylosing spondylitis studies by Braun and colleagues suggested that either etanercept or infliximab could prevent episodes of uveitis, but the data suggest that infliximab might be superior in this regard (9). Since adalimumab is a relatively new medication, information regarding its efficacy in the treatment of uveitis is scant, but the results from small retrospective case series of JIA-related uveitis appear promising (29,30). 3250 LIM ET AL Three recent retrospective studies seem to further support the possibility of a differential effect of these agents in the treatment of uveitis.…”

Abatacept for severe anti–tumor necrosis factor α refractory juvenile idiopathic arthritis–related uveitis

“…Adalimumab, a fully human anti-TNF␣ agent, seems to have comparable efficacy but better tolerability than infliximab; however, 20 -35% of patients, usually those with a longer duration of JIA-related uveitis, seem to be resistant to this treatment (6).…”

“…Despite improvements in the treatment strategy for arthritis, less progress has been made in the treatment of uveitis, which remains one of the greatest challenges encountered by pediatric rheumatologists and ophthalmologists. Although first-line treatment for uveitis consists of topical and oral steroids with methotrexate (MTX) for more severe uveitis (2), treatment with cyclosporin A (CSA) (3), mycophenolate mofetil (MMF) (4), and, more recently, anti-tumor necrosis factor (anti-TNF) agents such as infliximab (5) and adalimumab (6), has been proposed.…”

Infliximab to Treat Chronic Noninfectious Uveitis in Children: Retrospective Case Series with Long-term Follow-up

“…In one report, 18 children treated with adalimumab and background immunosuppression for a median of 17 months had fewer uveitis recurrences during adalimumab therapy than in the two years prior to treatment; other ocular outcome measures were not assessed. 11 In another series, 14 children were treated with adalimumab for a mean of 18 months; 81% demonstrated decreased anterior chamber flare and 65% achieved sustained control of inflammation. Incomplete information was provided regarding concomitant immunosuppressive treatment.…”