Superior efficacy of Adalimumab in treating childhood refractory chronic uveitis when used as first biologic modifier drug: Adalimumab as starting anti-TNF-α therapy in childhood chronic uveitis

Abstract

Background: Nonetheless biologic modifier therapies are available treatment strategies for sight-threatening uveitis in children, the lack of evidence from head-to-head randomized controlled studies limits our understanding of timing of therapy when to commence therapy, which agent to choose and how long to continue treatment, and, in case of failure, if switching to another anti-TNF-α strategy might be eventually an option. Our aim was to compare the efficacy of Adalimumab when used as first anti-TNFα therapy versus Adalimumab used after the failure of a previous anti-TNFα (Infliximab) in an open-label, comparative, multi-center, cohort study of childhood chronic uveitis.

Methods: 26 patients (14 F, 12 M; median age: 8.6 years) with refractory, non-infectious active uveitis were enrolled. Due to the refractory course of uveitis to previous DMARD treatment, Group 1 received Adalimumab (24 mg/sq mt, every 2 weeks), as first anti-TNFα choice; Group 2 received Adalimumab, as second anti-TNFα drug, due to the loss of efficacy of Infliximab, administered after a period of at least 1 year. Both groups received Adalimumab for at least 1 year of treatment. Primary outcome was, once remission was achieved, the time to a first relapse.

Results: 14 children (10 with JIA, 3 with idiopathic uveitis, 1 with Behçet's disease) were recruited in Group 1; 12 children (7 with JIA, 3 with idiopathic uveitis, 1 with early-onset sarcoidosis, 1 with Behçet's disease) in Group 2. Group 2 showed a lower probability to steroid discontinuation during the first 12 months of treatment (Mantel-Cox χ(2)4.12, p<0.04). In long-term follow-up, Group 1 had higher probability of uveitis remission during the time of treatment on Adalimumab (median ±SE: 18 ±1.1 vs 4 ±0.6 months, CI 95%: 15.6-27.5 vs 2.7-5.2, Mantel-Cox χ(2)10.12, p<0.002).

Conclusions: Even if limited to a relatively small group, our study suggests a better efficacy of Adalimumab when used as first anti-TNFα treatment in childhood chronic uveitis.

Keywords: Adalimumab; Children; Chronic uveitis; Infliximab.

Figure 1

Time to steroid discontinuation and time on remission up to the first relapse on Adalimumab. a. Survival curves of time to steroid discontinuation (months) for the Group 1 (black curve), receiving Adalimumab, as first anti-TNFα therapy, and the Group 2 (grey curve), receiving Adalimumab as second anti-TNFα therapy. On the y-axis, the probability of patient being on steroid treatment is shown. (log-rank, Mantel-Cox χ² 4.12, p < 0.004). b. Survival curves up to the first uveitis relapse on therapy after achieving remission (months) for Group 1 (black curve), receiving Adalimumab as first anti-TNFα therapy, and Group 2 (grey curve), receiving Adalimumab as second anti-TNFα therapy. On the y-axis, the probability of patient being on remission on anti-TNF-α therapy is shown (log-rank, Mantel-Cox χ² 10.12, p < 0.002).

Figure 2

Improved and normal visual acuity on Adalimumab. a-b. Number of children (a) as well the number of eyes (b) with improved (black bar) and not improved (white bar) visual acuity at 1 year of treatment in Group 1, receiving Adalimumab as first anti-TNFα therapy, and Group 2, receiving Adalimumab as second anti-TNFα therapy. (χ²: 11.5, p < 0.001; and χ²: 12.7, p < 0.001, respectively). c-d. Number of children (c) as well number of eyes (d) with normal (black bar) and abnormal (white bar) visual acuity at 1 year of treatment in Group 1, receiving Adalimumab as first anti-TNFα therapy, and in Group 2, receiving Adalimumab as second anti-TNFα therapy (χ²: 4.9, p < 0.04; and χ²: 6.4, p < 0.02, respectively).