Non-anti-TNF biologic modifier drugs in non-infectious refractory chronic uveitis: The current evidence from a systematic review
Introduction
Non-infectious chronic uveitis is a serious and disabling sight-threatening disease accounting for up to 10% of pathologies leading to blindness [1]. Currently, a step-by step escalating immunosuppressive therapy is generally used, in children as well as in adults, and anti-TNFα biologic therapies have markedly increased the treatment options for sight-threatening uveitis refractory to conventional immune-modulatory therapy (DMARD) in addition to topical and/or systemic corticosteroids [2], [3]. However, a subset of patients fails to respond to TNFα blockers or is unable to tolerate these therapies and may therefore benefit from switching to another drug [4], [5]. Overall, about 25% of children with autoimmune chronic uveitis (ACU) who received adalimumab and infliximab do not respond to these treatments [6]. In this clinical setting, the availability of several different molecules, mostly off-label, poses the clinical question whether it can be useful and safe to administer another class of biologic drugs, such as abatacept or rituximab, for patients with refractory autoimmune uveitis. To the best of our knowledge, to date, there has been no systematic evaluation on this topic. However, efficacy, availability of systemic treatments, as well as their potential side effects can be different between adults and children. The aim of our study was therefore to examine, separately, in children and adults with autoimmune chronic uveitis (ACU), the evidence regarding the effectiveness and the safety of switching to a non-anti-TNF biologic response modifier immunosuppressant treatment (NTT) currently available in clinical practice.
Section snippets
Methods
A systematic review was conducted and is reported according to the PRISMA guidelines.
Results
A total of 526 articles were identified by searches of databases, and, from these, 442 were excluded by examination of their titles and abstracts (Fig. 1). Excluded studies were mainly duplicates, studies on diseases other than autoimmune non-infectious uveitis (i.e., scleritis or inflammatory orbital diseases), studies on overall mortality among patients receiving immunosuppressive treatment, and studies on biologic modifier treatment other than NTT. Full text of the remaining 84 studies and 5
Discussion
We have estimated that the overall probability of improvement of uveitis, in both children and in adults, with ACU, refractory to previous DMARD and/or anti-TNFα treatments, treated with a NTT strategy, is 0.66. This evidence suggests that NTT agents can be efficacious treatment in this specific clinical setting. No eligible children received tocilizumab or alemtuzumab, and no adult received an anti-IL-1-blocking strategy. In both the age groups, there were not enough data to attempt a powered
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2017, Journal of PediatricsCitation Excerpt :Finally, the severity of pediatric uveitis encourages the development of new therapeutic agents. Some results are promising, such as anti-interleukin 1 medication (gevokizumab) for Behçet disease related uveitis12,40-42 and anti-interleukin 6 (tocilizumab) for various etiologies of uveitis.12,43 The strengths of our study included the high number of patients with non-JIA uveitis, the length of follow-up, which allowed critical analysis of the therapeutic strategies, and the presence of homogenous data obtained through close cooperation with our ophthalmologists.
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